Study characteristics

Methods

Study design: prospective, randomized study.

Study dates: study dates not available

Setting: outpatient, multicenter, national

Country: France

Participants

Inclusion criteria: male participants:

• Age ≥ 50 years

• Voiding disorders for at least 3 months before inclusion

• No suspicion of prostatic cancer (assessed by digital rectal examination)

• Prostate weight between 30 and 80 g

• Peak Flow Rate (PFR) < 15 mL/s for a voided volume ≥ 150 mL determined by 2 urine flow measurements

• Residual urine volume < 300 mL

• Prostate‐specific antigen (PSA) level < 1 0ng/mL for a prostatic weight < 60 g or a PSA level < 15 ng/mL for a prostatic weight ≥ 60 g

• Serum creatinine level < 160 pmol/L

• No infection (assessed by bacteriological analysis of urine)

• Written informed consent

Exclusion criteria: men with

• Undergone previous surgery on the prostate or bladder

• Mental incapacity

• Any chronic disease potentially hindering follow‐up

• Diabetes

• Participation in any clinical protocol within the last 3 months

• Any other urological disease

• Any medical treatment for voiding disorders within 15 days of inclusion

• Taken diuretics in the previous 3 months

• Anticoagulant therapy

• Allergy to lidocaine

• Colorectal disease.

Total number of participants randomized: 200

Group 1: n = 66 Transurethral route Hyperthermia

• Age, mean (SD): 65 (8) years

• Serum creatinine, mean (SD): 100 (19) mol/L

• Prostate weight, Mean (SD): 45 (15) g

• PSA, Mean (SD): 4.5 (2.7) ng/mL

• PFR, mean (SD): 10.4 (2.7) mL/s

Group 2: n = 31 transurethral sham

• Age, mean (SD): 66 (7) years

• Serum creatinine, mean (SD): 92 (16) mol/L

• Prostate weight, Mean (SD): 44 (11) g

• PSA, Mean (SD): 4.2 (3) ng/mL

• PFR, mean (SD): 9.9 (2.5) mL/s

Group 3: n = 65 Transrectal route hyperthermia

• Age, mean (SD): 66 (7) years

• Serum creatinine, mean (SD): 92 (19) mol/L

• Prostate weight, Mean (SD): 45 (13) g

• PSA, Mean (SD): 4.8 (2.8) ng/mL

• PFR, mean (SD): 9.8 (2.7) mL/s

Group 4: n = 38 transrectal sham

• Age, mean (SD): 66 (7) years

• Serum creatinine, mean (SD): 90 (19) mol/L

• Prostate weight, Mean (SD): 43 (15) g

• PSA, Mean (SD): 5.0 (3.3) ng/mL

• PFR, mean (SD): 9.0 (3.3) mL/s

Interventions

Group 1 (n = 66) TUMT

3 devices were used for transurethral treatment (Thermex II, Technorex, Israel: Prostcare, Brucker Spectrospin, France; BSD‐50. BSD Medical Corp, USA). Prostate temperature was monitored by an integrated microwave generator and controlled in each device through a fibreoptic temperature monitor. All devices were used according to the manufacturer's instructions to deliver a temperature compatible with hyperthermia treatment (45 °C). Treatment was delivered in 1 session of 1 to 3 hs (depending on the device used)

Group 2 (n = 31) Sham TUMT:

Sham treatment consisted of a single session with the temperature maintained at 37 °C

Group 3 (n = 65) Transrectal route hyperthermia:

3 devices were used for transrectal treatment (Prostathermer system, Biodan Medical Systems, Israel: Prostcare, Brucker Spectrospin, France: Primus, Tecnomatix Medical, Belgium). Prostate temperature was monitored by an integrated microwave generator and controlled in each device through a fibreoptic temperature monitor. All devices were used according to the manufacturer's instructions to deliver a temperature compatible with hyperthermia treatment (45 °C). Treatment was delivered in 6 sessions of 1 to 3hs (depending on the device used) for each session over 3 weeks

Group 4 (n = 38) transrectal sham: sham treatment consisted of a single session with the temperature maintained at 37 °C

Co‐interventions: not reported

Outcomes

Urologic symptom scores

How measured: Madsen score. Additionally, responders were participants showing excellent, good or moderate responses according to each of the criteria analyzed separately (Madsen score decrease > 30%; a PFR > 10 mL/s with a PFR increase > 30%)

Time points measured: baseline, 3, 6 and 12 months

Time points reported: baseline and 12 months

Subgroups: none

Retreatment

How measured: number of participants with medical or surgical procedure (reported the numbers separately for each)

Time points measured: during treatment and 1 to 4 weeks after treatment (early post‐treatment complications)

Time points reported: during treatment and 1 to 4 weeks after treatment (early post‐treatment complications)

Subgroups: none

Major and minor adverse event/acute urinary retention

How measured: number of participants with urethral bleeding, pain and urinary tract infection, acute urinary retention

Time points measured: during treatment and 1 to 4 weeks after treatment (early post‐treatment complications)

Time points reported: during treatment and 1 to 4 weeks after treatment (early post‐treatment complications)

Subgroups: none

Relevant outcomes not reported in this study

• Quality of life

• Erectile function

• Ejaculatory function

• Indwelling urinary catheter

Funding sources

This study was supported by a grant from the Comite d’Evaluation et de Diffusion des Innovations Technologiques (CEDIT), Assistance Publique‐Hopitaux de Paris. Devices were lent by the following companies: Biodan, Brucker, BSD, Direx and Tecnomatix

Declarations of interest

Not available

Notes

We only included transurethral active and sham groups for the purpose of this review. No contact information available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “Randomization was stratified by the investigating centre and by approach (transrectal or transurethral), and was performed using permutation tables such that equal sample sizes were obtained for each type of approach, device and sham group”

Comment: The investigators describe a random component in the sequence generation process.

Allocation concealment (selection bias)

Unclear risk

Quote: “Patients were randomly allocated to a treatment in a single treatment centre after verification of the inclusion criteria.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “Patients were not informed of their treatment, nor was the investigator who enrolled the patients.”

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Quote: “Patients were not informed of their treatment, nor was the investigator who enrolled the patients.”

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Quote: “Patients were not informed of their treatment, nor was the investigator who enrolled the patients.”

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
All outcomes

High risk

There is an imbalance in numbers or reasons for missing data across intervention groups and potentially inappropriate application of simple imputation.

Quote: “Patients lost to follow‐up were classified according to maximum bias (in the sham groups as 'responders' and in the hyperthermia groups as 'non‐responders').”

Comment: Missing data only in group 2.

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’

Other bias

Low risk

The study appears to be free of other sources of bias.

Study characteristics

Methods

Study design: prospective, randomized parallel study

Study dates: study dates not available

Setting: outpatient, single‐centre, national

Country: United Kingdom

Participants

Inclusion criteria: men with:

• Symptomatic uncomplicated BPH: > 1‐year history

• American Urological Association (AUA) score ≥ 12

• Flow rate < 15 mL/s

• Post‐void residual urine volume (PVR) < 300 mL

• Voiding pressure at maximal flow (Pdet max) 70 cmH2O

• Prostate volume 25 – 100 mL

• Obstructed as assessed on the Abrams‐Griffith nomogram

• Aged ≥ 55 years

• Informed consent

• Suitable for either treatment

Exclusion criteria: men with:

• General (e.g. mental incapacity, severe cardiovascular disease, ‘active’ drugs); technically unsuitable; metallic implants; cardiac pacemaker; rectal surgery or disease (except hemorrhoids), pelvic mass or surgery; previous prostatic surgery; prostatic abscess; uncontrolled coagulation disorder; active UTI

• Urological: prominent middle lobe; meatal stricture; previous drug treatment for BPH

• ‘Complicated’ BPH: acute or chronic urinary retention; upper tract dilatation; obstructive uropathy (serum creatinine > 150 mmol/L); bladder calculi; bladder diverticulae; recurrent UTI; recurrent prostatic hematuria

Total number of participants randomized: 60

Group 1: n = 30 transurethral microwave thermotherapy (TUMT)

• AUA score, median (range): 18.5 (17.1 – 20.1)

• Age, median (range): 69.36 years (56 – 88)

• Prostate volume, median (IQR): 36.6 mL (31.8 – 41.4)

• Qmax, median (range): 10.1 mL/s (9.2 – 10.9)

Group 2: n = 30 transurethral resection of the prostate (TURP)

• AUA score, median (range):18.4 (16.7 – 20.1)

• Age, median (range): 69.45 years (58 – 82)

• Prostate volume, median (IQR): 46.1 (38.1 – 54.1)

• Qmax, median (range): 9.5 mL/s (8.9 – 10.1)

Interventions

Group 1 (n = 30): TUMT

Done by a single operator using the Prostatron treatment catheter using the Prostasoft software (TechnoMed, Lyon, France) in a single 60‐min session under topical anesthesia with Instillagel(r) (FarcoPharma GmBH, Cologne, Germany)

Group 2 (n = 30): TURP

Performed on the routine operating lists by a surgeon of Senior Registrar grade or above using a standard technique. No post‐operative irrigation was used and all the resected tissue was submitted for histological examination. The urethral catheter was removed 3 or 4 days after surgery

Co‐interventions: “Intramuscular gentamicin (80 mg) was given before the treatment and oral trimethoprim (200 mg twice daily) was continued for 5 days. The participants were followed up at 6 weeks, 3 and 6 months, with a detailed evaluation performed at the last assessment.”

Outcomes

Urologic symptom scores

How measured: AUA symptom score

Time points measured: baseline, 6 weeks, 3 and 6 months

Time points reported: not reported (probably 6 months)

Subgroups: none

Indwelling urinary catheter/acute urinary retention

How measured: number of participants requiring an indwelling catheter after treatment due to acute urinary retention

Time points measured: 6 weeks, 3 and 6 months

Time points reported: not reported

Subgroups: none

Major adverse event

How measured: number of participants requiring blood transfusions after treatment.

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Minor adverse event / erectile function / ejaculatory function

How measured: number of participants developing urinary tract infections or meatal narrowing that required dilatation. Adverse events related to erectile function and ejaculation are described under adverse events

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Relevant outcomes not reported in this study

• Quality of life

• Retreatment

Funding sources

Not available

Declarations of interest

Not available

Notes

No contact information available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “[...] patients were randomized to each treatment by selecting a sealed envelope. [...] Patients failing to complete treatment or return for follow‐up were substituted.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

High risk

Quote: “[...] patients were randomized to each treatment by selecting a sealed envelope. [...] Patients failing to complete treatment or return for follow‐up were substituted.”

Comment: Whereas envelopes might be sealed, substitution might indicate tampering of allocation.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure). The objective outcomes were unlikely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

High risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure). The subjective outcomes were likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Due to “substitution” noted above, the number of participants with missing outcome data was not provided.

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were detected.

Study characteristics

Methods

Study design: parallel‐group randomized trial

Study dates: study dates not available

Setting: outpatient/inpatient – national/multicenter

Country: USA

Participants

Inclusion criteria:

• Male participants aged 50 ‐ 80 years

• AUA index > 13 and a bother score > 11

• PFR 12 < 12 mL/sec and PVR >125 mL

• Prostate size between 30 and 100 cc

• Without a significant intravesical middle lobe (all patients underwent cystoscopy)

Exclusion criteria: none described

Total number of participants randomly assigned: 190

Group 1: 125 (TUMT)

• Age (mean ± SD): 65.2 ± 7.3 years

• Prostate volume (mean ± SD): 50.5 ± 18.6 mL

• PSA (mean ± SD): 2.6 ± 1.8 ng/mL

• AUA‐SI (mean ± SD): 22.2 ± 5.0

• Qmax: 8.9 ± 3.0 mL/second

Group 2: 65 (Sham)

• Age (mean ± SD): 64.6 ± 7.1 years

• Prostate volume (mean ± SD): 47.1 ± 17.9 mL

• PSA (mean ± SD): 47.1 ± 17.9 ng/mL

• AUA‐SI (mean ± SD): 22.7 ± 5.7

• Qmax: 8.4 ± 2.0mL/second

All participants were men

Interventions

Group 1 (n = 125): TUMT

The TherMatrx TMx‐2000 device with the RX‐200 prostate applicator was used for heating and monitoring (with 2 thermo‐sensor tracks on the surface of the catheter). The RX‐200 was inserted, balloon inflated, and a drainage lumen connected to a collection bag. The length from the bladder neck to the verumontanum was measured by ultrasound. Temperature reached a peak of 50 ºC to 55 ºC with a monitoring of rectal temperature (< 42.5 ºC). A Foley catheter inserted into the bladder was left in place from 2 to 4 days

Group 2 (n = 65): Sham

Participants underwent placement of the microwave catheter for the treatment period without energy delivery and received the same post‐treatment care as the active‐treatment participants

Co‐interventions: ketorolac 10 mg, narcotic agents, lorazepam 2 mg before treatment. Lidocaine jelly was applied to the urethra for 15 minutes Alpha‐blockers were not permitted

Outcomes

Urologic symptoms score

How measured: AUA‐SI score

Time points measured: baseline, 1, 3, 6, 9 and 12 months

Time points reported: baseline, 3, 6, 12 months (for Group 1), baseline and 3 months (for Group 2)

Subgroups: none

Major and minor adverse event / ejaculatory function / acute urinary retention

How measured: major and minor adverse events, including ejaculatory adverse events and recatheterization; all described narratively

Time points measured: not reported

Time points reported: at 3 months

Relevant outcomes not reported in this study:

• Quality of life: only measured and reported for Group 1

• Retreatment

• Erectile function

• Indwelling urinary catheter: not applicable (per protocol all participants were catheterized for 2 to 4 days)

Funding sources

Not available

Declarations of interest

Not available

Notes

Patients were unblinded at 3‐month follow‐up and then crossed over to active treatment in a second phase. Only the first phase was included in our review.

Other measured outcomes: AUASI bother, urinary flow rates, PUR, PSA and TRUS.

The 5‐year follow‐up study (presented at a conference) only included data on the active treatment arm.

Contact information Dr. Albala: [email protected]

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

2:1 randomizations. No other information available. Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’. We wrote to study authors.

Allocation concealment (selection bias)

Unclear risk

No information available. Insufficient information to permit judgement of ‘Low risk’ or ‘High risk’. We wrote to study authors.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: “All patients were blinded as to their group assignment, and outcome analysis was performed by individuals blinded to the randomisation.”

Comment: it is unclear whether personnel were blinded. We wrote to study authors.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Quote: “All patients were blinded as to their group assignment, and outcome analysis was performed by individuals blinded to the randomisation.”

Comment: it is unclear whether personnel were blinded, but the outcomes are unlikely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Quote: "All patients were blinded as to their group assignment, and outcome analysis was performed by individuals blinded to the randomisation."

Comment: participants (outcome assessors of subjective outcomes) were blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Urologic symptom score: outcome data available for 125/125 participants in Group 1 and 63/65 participants in Group 2. Presumably similar attrition in other outcomes.

Selective reporting (reporting bias)

High risk

Protocol not available ‐ outcome data (urologic symptom score) was not available for Group 2 at time points beyond 3 months. Quality‐of‐life data were not available for Group 2. We wrote to study authors.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: prospective, randomized parallel study

Study dates: study dates not available

Setting: outpatient, single‐center, national

Country: United Kingdom

Participants

Inclusion criteria: men with:

• Symptoms of prostatism for at least 6 months

• World Health Organization's symptom score > 14

• Residual urine volume of at least 50 mL

• Peak flow rate < 15 mL/s

Exclusion criteria: men with:

• Malignant glands

• Impaired renal function

• History of prostatic surgery

• Residual urine volumes > 200 mL

• Large glands (length from bladder neck to proximal veru > 40 mm)

• Large obstructing middle lobes

• Acute urinary retention

• Coexisting urinary tract disease

Total number of participants randomized: 40

Group 1: n = 22 microwave treatment

• World Health Organization's symptom score, mean (95% CI): 30 (25.2 – 34.8)

• AUA symptom score, mean (95% CI): 19.2 (16.3 ‐ 22.1)

• Age, mean: 63.7 years (no 95% CI or SD available)

• Qmax, mean (95% CI): 12.3 mL/s (10.7 – 13.9)

• Residual vol, mean (95%CI): 104 mL (85 ‐ 125)

Group 2: n = 18 sham treatment

• World Health Organization's symptom score, mean (95% CI): 31 (25.5 – 36.5)

• AUA symptom score, mean (95% CI): 18.8 (16.0 ‐ 21.7)

• Age, mean: 62.6 years (no 95% CI or SD available)

• Qmax, mean (95% CI): 10.8 mL/s (9.2 – 12.4)

• Residual vol, mean (95% CI): 80 mL (57 ‐ 103)

Interventions

Group 1 (n = 22):TUMT

LEO Microthermer was used in all participants in a single active 90‐min treatment. This machine delivers a maximum power output of 20 watts at 915 MHz. and incorporates an automatic power cut‐off, which operates if the rectal temperature increases to > 42.5 ºC

Group 2 (n = 18) Sham: Same procedure, participants received 90‐min sham treatment with no power delivered. Participants received a heating pad to simulate hyperthermia

Co‐interventions: topical lidocaine gel was used alongside flexible cystoscopy to exclude a coexisting lower urinary tract pathological condition and to measure the prostate

Outcomes

Urologic symptom scores

How measured: AUA symptom score and WHO symptom score. Also as the proportion of participants with a decrease of 50% or more in symptom scores.

Time points measured: baseline and 3 months

Time points reported: baseline and 3 months

Subgroups: none

Minor and major adverse events / erectile function / ejaculatory function

How measured: Narratively (including sexual adverse events)

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Acute urinary retention

How measured: narratively

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Retreatment

How measured: narratively (TURP after sham)

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Relevant outcomes not reported in this study

• Quality of life

• Indwelling urinary catheter

Funding sources

Not available

Declarations of interest

Not available

Notes

Study unblinded with cross‐over at 3 months and follow‐up to 1 year. 16 participants in the sham group were offered active treatment at 3 months (this was not considered retreatment). No contact information available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

The study describes only "sealed envelope." Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind study. Participants and study personnel were blinded.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Double‐blind study. Participants and study personnel were blinded.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Double‐blind study. Participants and study personnel were blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Only 2 participants (10%) in the sham group were lost at follow‐up.

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: parallel‐group randomized trial

Study dates: study dates not available

Setting: outpatient

Country: USA

Participants

Inclusion criteria: men with:

• Urinary symptoms (Madsen Symptom score > 8)

• PVR between 100 and 200 mL

• PFR < 10 mL/s

• Prostate length between 35 and 50 mm on ultrasound examination

Exclusion criteria: men receiving medication for:

• Metallic implants

• Conditions suggesting neuropathic bladder

• Evidence of prostate cancer previous surgery (rectal or transurethral)

• Antiandrogen therapy

• Serum creatinine > 2 mg/dL

• Urinary retention

• Bladder stones

• Uncontrolled dysrhythmias or cardiac pacemakers

• Asymmetric median lobe enlargement

Total number of participants randomized: 115

Group 1 (n = 78) TUMT

• AUA score, mean (SD): 19.9 (7.2)

• Age, mean (SD): 66.9 (7.8) years

• Prostate volume, mean (SD): 37.4 (14.2) mL

• Qmax, mean (SD): 1.3 (1.6) mL/s

Group 2 (n = 37) sham

• AUA score, mean (SD): 20.8 (6.7)

• Age, mean (SD): 66.9 (7.1) years

• Prostate volume, mean (SD): 36.1 (13.4) mL

• Qmax, mean (SD): 7.4 (1.7) mL/s

Interventions

Group 1 (n = 78): TUMT

Prostatron device is inserted by a 20F transurethral applicator (with 2 cooling channels) catheter and a rectal probe confirmed by ultrasonography. The treatment catheter emits a radiofrequency of 1296 MHz. The treatment consist of 3 stages: 1) cooling (to 27 ºC); 2) microwave emission to a threshold of 42.5 ºC rectal temperature; 3) progressive cooling. These details were provided in the report of a previous non‐randomized study (Blute 1993)

Group 2 (n = 37): Sham

This consisted of circulation of urethral coolant without application of microwave power while a sham treatment was displayed on the computer monitor. and the program run for 60 minutes

Co‐interventions: Participants were given anti‐inflammatory agents and prophylactic antibiotics before and after (7 days) the procedure. If the participant experiences difficulties, a Foley catheter was inserted. Sedation was used at discretion (no sedation in 89% of TUMT sessions, and 100% of sham sessions)

Outcomes

Urologic symptom scores

How measured: Madsen Symptom score / AUA symptom score

Time points measured: baseline, 6 weeks, 3, 6 and 12 months

Time points reported: baseline, 6 weeks, 3, 6 and 12 months (mostly graphically; comparative outcome data were only available at 3 months)

Minor adverse events (including erectile/ejaculatory function)

How measured: narratively including sexual adverse events

Time points measured: at complete follow‐up (12 months)

Time points reported: at complete follow‐up (12 months)

Acute urinary retention/Indwelling urinary catheter

How measured: narratively

Time points measured: at complete follow‐up (12 months)

Time points reported: at complete follow‐up (12 months)

Relevant outcomes not reported in this study:

• Retreatment

• Quality of life

• Indwelling urinary catheter

• Major adverse events were not adequately described

Funding sources

Not available

Declarations of interest

Not available

Notes

Whereas the blinding lasted for 3 months, the follow‐up time was 12 months.

The reporting of outcomes was not disaggregated by group (intervention versus sham, but for the entire population) for most outcomes and time points.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: “The patients were randomized to TUMT or sham treatment in a 2:1 ratio based on a permuted‐blocks procedure.”

Allocation concealment (selection bias)

Low risk

Quote: “Randomization assignments were distributed in sealed envelopes identified only by a unique patient number. The treating physician opened the envelope after completing all screening tests just prior to treatment.”

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “To blind the evaluating physician to the patient's actual treatment, data on the treatment received (including post‐treatment PSA values) were not entered in the patient's study chart until after the 3‐month evaluation.” “Physicians and paramedical personnel behaved in the same fashion they would have during real thermotherapy sessions.”

Comment: There was also “blinding verification” at 1 week after procedure:
Quote: “When patients were queried about the treatment they had received, only half of the TUMT patients (51.3%; 40 of 78) guessed correctly, and in the sham‐treatment group, less than half of the patients (44.4%; 16 of 36) guessed correctly (Table 2).”

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Double‐blind study ‐ see above.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Double‐blind study ‐ see above.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote: “Of the 150 patients treated 118 had Madsen symptom score data at 12 months, since 11 discontinued the study or were lost to follow up, 16 were re‐treated with the Prostatron unit, 4 received alternative therapy (3 underwent transurethral procedures, and 1 received terazosin) and 1 was missing a Madsen score at followup.”

Comment: High attrition date for 'Urinary Symptoms Score' (21%). There is no specification about attrition by group.

Selective reporting (reporting bias)

High risk

No protocol available. Data were presented graphically for most time points. Comparative outcome data were only available at 3 month‐follow up for some outcomes.

Other bias

Low risk

No other sources of bias were detected.

Study characteristics

Methods

Study design: prospective, randomized parallel study

Study dates: study dates not available

Setting: outpatient, single‐center, national

Country: Sweden

Participants

Inclusion criteria: men with low urinary tract symptoms dominated by:

• Hesitancy

• Slow urination

• Enlarged prostate

• Maximum flow‐rate (Q ) of < 12 mL/s

Exclusion criteria: men with:

• Indwelling catheter

• Median prostatic lobe

• Prostate gland estimated as > 50 g

• Suspected prostatic malignancy

• Neurological disease

• Previous surgery for prostatic disease

Total number of participants randomized: 44

Age, mean (range): 70.4 (53 – 83) years. (No disaggregated data by group reported)

Group 1: n = 16 60‐min TUMT

ICS questionnaire A: 49 (of a maximum of 124) (see notes)

ICS questionnaire B: 36 (of a maximum of 92) (see notes)

Qmax: 7mL/s

Group 2: n = 14 30‐min TUMT

ICS questionnaire A: 58 (of a maximum of 124) (see notes)

ICS questionnaire B: 40 (of a maximum of 92) (see notes)

Qmax: 8.7 mL/s

Group 3: n = 14 Sham

ICS questionnaire A: 46 (of a maximum of 124) (see notes)

ICS questionnaire B: 36 (of a maximum of 92) (see notes)

Qmax: 7.9 mL/s

Interventions

Group 1 (n = 16): 60‐min TUMT

ECP system (Comair, Sweden) equipped with a microwave antenna (915 MHz), a fibreoptic system for measuring the temperature in the urethra and, by a rectal probe, in the rectum. It contained a circulating cooling system that reduced the heat delivered to the urethral wall with a maximum heating at 30 s and a temperature limit of 46 °C in the urethra and of 43 °C in the rectum. After treatment, a voiding trial was attempted; if difficulties arose, a urethral catheter was inserted and left in place for three days.

Group 2 (n = 14):

Similar intervention as group 1, except that the duration of the session was 30 min.

Group 3 (n = 14): Sham

“Only water at 20 °C was circulated in the treatment catheter and a computer monitor, visible to the patient, showed a simulated heat‐treatment curve, similar to that produced during TUMT.”

Co‐interventions: Antibiotics (norfloxacin).

Outcomes

Minor and major adverse event

How measured: number of participants suffering a bacterial cystitis despite antibiotic treatment

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Retreatment

How measured: number of participants requiring other treatment within the follow‐up year

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Relevant outcomes not reported in this study:

• Urologic symptom scores: ICS questionnaires, results were not adequately reported (as percentage of change from baseline)

• Quality of life

• Erectile function

• Ejaculatory function

• Acute urinary retention/indwelling urinary catheter (no disaggregated data by group)

Funding sources

Not available

Declarations of interest

Not available

Notes

ICS questionnaire consists of 32 questions, most of which comprise an ‘A’ question about the actual symptom and a ‘B’ question about the bother related to the symptom. The questionnaire also includes several questions about sexual function (nos 24 – 27); these were all excluded from the instrument used in the present study. The maximum A and B scores are 124 and 92, respectively; a high score indicates worse symptoms.

2 participants withdrew during the 1‐year study period, leaving 42 for the final evaluation.

No contact information available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “The patients were randomised to undergo 30 or 60 min of TUMT, or to sham treatment (14, 16 and 14 men, respectively).”

Comment: Insufficient information about the sequence generation process to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Insufficient information about the sequence generation process to permit judgment of ‘Low risk’ or ‘High risk’

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

No information about blinding of personnel.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

The participants were blinded: “study where the patients were unaware of the type of treatment given.”

Comment: Outcomes are unlikely to be affected by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

The participants were blinded: “study where the patients were unaware of the type of treatment given.”

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Insufficient reporting of attrition/exclusions to permit judgment of ‘Low risk’ or ‘High risk’.

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: parallel‐group randomized trial

Study dates: January 1994 to August 1995

Setting: outpatient

Country: Netherlands

Participants

Inclusion criteria: men:

• 45 years old or older

• Clinically unequivocal benign prostate

• Prostatic length 25 to 50 mm – volume 30 to 100 cm³

• Symptoms > 3 months

• Madsen symptom score 8 or greater

• PFR peak flow rate 15 mL per second

• Minimum voided volume of 100 mL

• Post‐void residual 350 mL or less

• Willingness and ability to comply with the study follow‐up

Exclusion criteria:

• Neurogenic disorders that may affect bladder function

• Prostatic carcinoma

• Prior surgery of the prostate

• Microwave possible sensitive implants (pacemaker or hip prosthesis)

• Diabetic neuropathy

• Urinary retention requiring an indwelling catheter

• Renal impairment

• Obstructed bladder neck due to an enlarged median lobe of the prostate

• Those who were on medication prescribed for treatment of the prostate or bladder

Sample size: 52 participants were randomized

Group 1: n = 31 transurethral microwave thermotherapy (TUMT)

• Age, mean (SD): 69.6 ± 8.5

• Prostate volume (cc), mean (SD): 45 ± 15

• IPSS score, Mean (SD): 16.7 ± 5.6

• Qmax (mL/s), Mean (SD): 9.3 ± 3.4

• Residual volume, mL (SD): 91 ± 105

Group 1: n = 21 transurethral resection of the prostate (TURP)

• Age, mean (SD): 69.3 ± 5.9

• Prostate volume (cc), mean (SD): 43 ± 12

• IPSS score, Mean (SD): 18.3 ± 6.3

• Qmax (mL/s), Mean (SD): 10.0 ± 6.1

• Residual volume, mL (SD): 58 ± 78

Interventions

Group 1 (n = 31): TUMT

Delivered using Prostatron device with software version 2.5, for 60 minutes increasing thermal dose up to 70 watts. Urethral and rectal thermal sensors provided feedback to prevent harms. Preparation included 100 mg diclofenac suppository and 2 mg of midazolam intramuscularly. If necessary, further intravenous sedation was administered. All participants left with an indwelling urinary catheter

Group 2 (n = 21): TURP

Performed by 2 experienced urologists with use of spinal anesthesia. The surgical capsule was reached circumferentially from the bladder neck to the verumontanum using 24 Ch. Resectoscopes

Co‐interventions: not described

Outcomes

Urologic symptom scores

How measured: Madsen symptom score and IPSS

Time points measured: 1, 3, 6 and 12 months

Time points reported: 3, 6, 12 months

Subgroups: none

Major and minor adverse events

How measured: episodes of urinary tract infection, hematuria

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Retreatment

How measured: “repeat treatment”

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Indwelling urinary catheter

How measured: days of catheterization

Time points measured: not reported

Time points reported: median days and range

Subgroups: none

Relevant outcomes not reported in this study:

• Quality of life

• Erectile function

• Ejaculatory function

• Acute urinary retention (all participants were routinely catheterized)

Funding sources

Not available

Declarations of interest

Not available

Notes

No contact information available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “Participants were randomised”.

Comment: No information available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: “Participants were randomised.”

Comment: No information available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Participants and personnel were not blinded.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Participants and personnel were not blinded. Outcomes are unlikely to be affected by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

High risk

Participants and personnel were not blinded.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Outcome data were available for 44/52 participants at 1 year follow‐up, 2 were lost in the TURP group (bladder cancer and bladder neck sclerosis) and 6 in the TUMT group (1 underwent TURP, 1 died, 1 lost to follow up, 3 refused follow‐up). Unbalanced attrition.

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were detected.

Study characteristics

Methods

Study design: parallel‐group randomized trial

Study dates: study dates not available

Setting: outpatient (TUMT), inpatient (TURP), single‐center, national

Country: Sweden

Participants

Inclusion criteria: men:

• Candidate for TURP

• 45 years of age or older

• Benign prostate, length 35 ‐ 50 mm (ultrasound)

• Anesthesia risk group 1 ‐ 3 (ASA class 1‐3)

• Obstructive symptoms for > 3 months

• Madsen total symptom score of > 8

• 2 peak flow rates of < 15 mL/s (volume > 150 mL)

Exclusion criteria:

• Mental incapacity, dementia, or inability to give informed consent

• Neurological disorders which might affect bladder function

• Peripheral arterial disease (intermittent claudication or Leriches syndrome)

• Disorder of hemostasis or serum creatinine of > 2 mg/dl

• Uncontrolled cardiac arrhythmias or a cardiac pacemaker

• Total hip replacement or other metallic implants

• Indwelling or condom catheter

• Post‐void residual urine of > 350 mL

• Prostatic cancer or suspicion of prostatic cancer

• Large median lobe of the prostate

• Urethral stricture

• Bladder cancer (by cystoscopy or cytology)

• Bladder stones

• Previous rectal or pelvic surgery/radiotherapy

• Previous prostatic surgery or heat treatment

• Alpha‐adrenergic blockers (within 4 weeks), antiandrogen

• Medication (within 1 year) or other medication that may affect the prostate or bladder

• Bacterial prostatitis or urinary tract infection at the time of treatment

• Prostatic urethral length of < 35 or > 50 mm (transrectal ultrasound)

• Anesthesia risk category 4 or 5 (ASA class 4 or 5)

Total number of participants randomized: 93

Group 1 (n = 46) TUMT

• Mean age: 68 years

• Mean prostate volume: 33 mL

• Madsen symptom score, mean (SD): 11.2 (3.1)

• Peak urinary flow: 8.0 mL/s

• Postvoid residual: 105 mL

Group 2 (n = 47) TURP

• Mean age: 70 years

• Mean prostate volume: 37 mL

• Madsen symptom score, mean (SD): 13.3 (4.2)

• Peak urinary flow: 7.9 mL/s

• Postvoid residual: 116 mL

Interventions

Group 1 (n = 39): TUMT

1‐hour treatment in a single session performed by a single physician using the Prostatron (Technomed International, France) only with topical anesthesia and oral analgesia. The urethral catheter delivered up to 60 W of microwave energy and monitored temperature (as well as the rectal probe) through software. The urethral temperature could reach a maximum temperature of 44.5 °C and the rectal temperature could reach a maximum temperature of 42.5 °C. Postoperatively oral norfloxacin 400 mg twice a day was administered for 5 days. An indwelling urethral catheter was left in place for 3 ‐ 5 days if the participant was unable to void after treatment

Group 2 (n = 44): TURP

Urologists who were at the level of senior registrar or above resected the prostate, using resectoscopes with a Charrière of 24 ‐ 28, down to the surgical capsule circumferentially and extended from the bladder neck to the verumontanum

Co‐interventions: not reported.

Outcomes

Urologic symptom scores

How measured: Madsen symptom score

Time points measured: baseline, 2, 3, 6, 12 months, 2 years

Time points reported: baseline, 2, 3, 6, 12 months, 2 years

Subgroups: none

Major and minor adverse events (including erectile and ejaculatory function)

How measured: not reported

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Retreatment

How measured: number of participants that required another session of TUMT or TURP

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Indwelling urinary catheter

How measured: number of participants that required catheterization after the procedure.

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Relevant outcomes not reported in this study

• Quality of life

• Acute urinary retention

Funding sources

Not available

Declarations of interest

Not available

Notes

There are 2 reports of this study by the same authors. In the first report there are 83 randomized participants, whereas in the second report there are 72. We accounted this as attrition. Email for the contact author was not available, so we wrote to his coauthor Dr. Fall ([email protected]) for details, but he did not have this information.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “patients were recruited for the study and blindly randomised.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’. We wrote to study authors.

Allocation concealment (selection bias)

Unclear risk

Quote: “patients were recruited for the study and blindly randomised.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’. We wrote to study authors.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

Comment: The objective outcomes were unlikely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

High risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

Comment: The subjective outcomes were likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

12‐month follow‐up, 78 participants (93%) had available data (first report).

Quote: “Four patients were excluded; 1 patient because he contracted severe hepatitis while abroad precluding follow‐up; 2 patients because cancer was discovered at the time of histological examination of the TUR specimen requiring orchiectomy, and 1 patient who refused randomizations to TURP.”

Judgment (12 months): low risk of bias.

2‐year follow‐up, 61 participants (73%) had available data (second report).

Quote: “All patients were followed for 2 years but in 10 patients the follow‐up was incomplete. In the TURP group, one patient died from a brain tumour after his 6‐month follow‐up. At the 2‐year follow‐up, one patient underwent an operation for a lumbar disc hernia and was unavailable. In the TUMT group, one patient was abroad at the 3‐month follow‐up and after the 6‐month follow‐up, two patients had a TURP and were excluded from the study, one patient refused further follow‐up and another suffered severe pancreatitis which precluded that visit. Two patients who had undergone a second TUMT after the 6‐month follow‐up took part in the 1‐year follow‐up but had not improved and, after undergoing TURP, they were excluded before the 2‐year follow‐up. One patient was disabled due to severe neurological disease after the 1‐year follow‐up.”

Judgment (2 years): high risk of bias.

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’. We wrote to study authors.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: parallel group randomized trial

Study dates: Start date June 1991 – End date December 1992

Setting: outpatient, multicenter, international

Country: Netherlands and the United Kingdom

Participants

Inclusion criteria: men:

• Aged > 45 years

• Complaining of symptoms of bladder outlet obstruction for > 3 months

• With a Madsen symptom score of > 8

• Urinary free‐flow rate estimates of < 15 mL/s during 2 voids of > 150 mL

• Prostatic enlargement was confirmed by transrectal ultrasonography

• PSA or prostatic biopsy if necessary

Exclusion criteria:

• Prostate cancer

• Prostatitis

• Urethral stricture

• Intravesical pathology (stones, neoplasm)

• Neurogenic bladder dysfunction

• Urinary tract infection

• Isolated enlargement of the middle lobe

• A residual urine volume of > 300 mL

• Use of drugs influencing bladder or prostate function

• Previous transurethral resection of the prostate or transurethral incision

• A metallic pelvic implant

• Disorders of blood flow or coagulation

• Diabetes mellitus

• Mental incapacity or inability to give informed consent

Total number of participants randomized:93 men recruited but 90 were randomized (there is no further detail on the report)

Group 1: n = 46 TUMT

• Mean age (SD): 66.3 (8.1) years

• Prostate volume (SD): 48.6 (16.6) mL

• Madsen score (SD): 13.7 (3.4) points

• Peak Flow (SD): 9.2 (2.5) mL/s

• PVR (SD): 93.9 (75.4) mL

• Voided fraction (SD): 74.9% (16.6)

Group 2: n = 47 Sham

• Mean age (SD): 66.9 (6.0) years

• Prostate volume (SD): 49.0 (20.0) mL

• Madsen score (SD): 12.9 (3.1) points

• Peak Flow (SD): 9.6 (2.7) mL/s

• PVR (SD): 84.7 (66.1) mL

• Voided fraction (SD): 77.3% (15.7)

Interventions

Group 1 (n = 46): TUMT

A single session of Prostatron treatment unit which consisted of a microwave generator, urethral applicator/cooler, fiberoptic temperature‐monitor, and couch. This study used the lower energy thermotherapy protocol (Prostasoft 2.0)

Group 2 (n = 47): Sham

Same procedure as in TUMT with a simulated program

Co‐interventions: Not described

Outcomes

Urologic symptoms score

How measured: Madsen symptom score. Responder analysis (> 50% decrease in Madsen score)

Time points measured: baseline, 6, 12, 26, 52 weeks

Time points reported: baseline, 6, 12, 26, 52 weeks (cross‐over after 3 months)

Subgroups: none

Major and minor adverse event

How measured: major and minor adverse events

Time points measured: not reported

Time points reported: at 3 months

Acute urinary retention

How measured: number of participants that required a catheter after the procedure due to urinary retention

Time points measured: not reported

Time points reported: at 3 months

Relevant outcomes not reported in this study

• Quality of life: ad‐hoc questionnaire (not validated). This included questions of sexual function

• Erectile function (see “quality of life”)

• Ejaculatory function (see “quality of life”)

• Retreatment: participants in the sham group were offered TUMT after 3 months. It is not clear if this was due to failure in the treatment. 2 participants in the TUMT group received TURP

• Indwelling urinary catheter

Funding sources

Not available

Declarations of interest

Not available

Notes

This study reports the trial by location and globally. The quality‐of‐life results are only available for the Netherlands report.

After 3 months participants were offered TUMT. 27 participants in the Sham group and 4 participants in the TUMT group received a verum procedure, thus the results of this trial beyond 3 months are not included in this review.

No contact information available.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “Patients were randomised after informed consent was obtained.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: “Patients were randomised after informed consent was obtained.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “As far as possible, the patient and the investigator were kept unaware as to the treatment administered.” (first three months)

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Quote: “As far as possible, the patient and the investigator were kept unaware as to the treatment administered” (first three months).

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Quote: “As far as possible, the patient and the investigator were kept unaware as to the treatment administered” (first three months).

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Data were not available at 3 months for 3 participants in the Sham group (2 losses at follow‐up and 1 technical failure) and 2 participants in the TUMT group (underwent TURP).

Selective reporting (reporting bias)

Unclear risk

Protocol not available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: parallel‐group randomized trial

Study dates: start date January 1996 – end date March 1997

Setting: outpatient/inpatient, national, single‐center

Country: The Netherlands

Participants

Inclusion criteria: Male participants:

• Aged 45 years and older

• Prostate volume ≥ 30 cm³

• Prostatic urethral length ≥25 mm,

• A Madsen symptom score ≥8

• Maximum peak flow rate ≤ 15 mL/s

• A postvoid residual ≤ 350 mL

Exclusion criteria: men with:

• Acute prostatitis or urinary tract infection

• Evidence of prostate carcinoma

• An isolated obstructed prostatic middle lobe

• Diabetes mellitus

• Intravesical pathology,

• Neurological disorders

• Current treatment with drugs that may influence the bladder function

Total number of participants randomly assigned: 155

Group 1 (n = 82) TUMT

• Age (mean and range): 68 (54 to 77) years

• Prostate volume (mean and range): 42 (30 to 82) mL

• PSA (mean ± SD): not reported

• IPSS (mean and range): 21 (10 – 28)

• Qmax (mean and range): 9.0 (5.0 – 14.0) mL/second

Group 2 (n = 73) TURP

• Age (mean and range): 66 (55 – 77) years

• Prostate volume (mean and range): 48 (31 – 84) mL

• PSA (mean ± SD): not reported

• IPSS (mean and range): 20 (11 – 29)

• Qmax (mean and range): 8.4 ± 2.0 mL/second

Interventions

Group 1 (n = 74): TUMT

A 1‐hour session was administered by the Prostatron device (EDAP Technomed, Lyon, France) with a second‐generation, high‐energy protocol (Prostasoft 2.5) with a maximum power of 70 W and a rectal threshold set at 43.5 °C. Participants were administered 40 mg of morphine sulphate orally 2 hours before treatment. All participants received an indwelling Foley catheter following an outpatient voiding trial. Participants also received co‐trimoxazole 960 mg twice a day for 5 days after treatment as prophylaxis

Group 2 (n = 73): TURP

It was performed under spinal anesthesia and intended to remove as much prostate tissue as possible; all participants received an indwelling Foley catheter, which was removed when hematuria decreased sufficiently, and the participant completed a successful voiding trial

Co‐interventions: not described

Outcomes

Urologic symptoms score

How measured: IPSS score and Madsen score

Time points measured: baseline, 3, 6, 12, 18, 24 and 36 months

Time points reported: baseline, 12, 24 and 36 months

Subgroups: none

Quality of life

How measured: 41‐item questionnaire designed for BPH patients

Time points measured: baseline, 1, 3, 6 and 12 months

Time points reported: baseline, 12 and 52 weeks

Subgroups: none

Retreatment

How measured: narratively

Time points measured: baseline, 3, 6, 12, 18, 24 and 36 months

Time points reported: 6, 12, 18, 24, 30 and 26 months

Major and minor adverse events

How measured: major and minor adverse events

Time points measured: not reported

Time points reported: at 3 months

Erectile function/ejaculatory function ("Sexual function")

How measured: ad‐hoc questionnaire that assessed erections, sexual activities, orgasms, and satisfactions, among other aspects

Time points measured: baseline, 3 months and 1 year

Time points reported: baseline, 3 months and 1 year

Relevant outcomes not reported in this study:

• Erectile function

• Ejaculatory function (“Ejaculatory dysfunction pain” was reported)

• Acute urinary retention

• Indwelling urinary catheter (per protocol all participants were catheterized for 2 to 4 days)

Funding sources

Not available

Declarations of interest

Not available

Notes

No contact information available.

We found a secondary report on sexual function with a greater attrition of data and with a slightly lower number of randomized individuals (147 participants versus 155 in the original report).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “All patients were randomised after informed consent had been obtained.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: “All patients were randomised after informed consent had been obtained.”

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label study

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Open‐label study. However, the outcomes are unlikely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

High risk

Open‐label study.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: “Although […] 155 patients initially randomised, unfortunately because of the 10 who skipped the assigned treatment and 1 who died before the scheduled treatment, we have no follow up information.”

Comment: Attrition was documented and was balanced (7 in the thermotherapy group and 11 in the TURP group) (low risk of bias)

Sexual function report: "A total of 66 patients undergoing transurethral microwave thermotherapy and 56 undergoing transurethral prostatic resection were evaluated" (high risk of bias).

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: prospective, randomized parallel study

Study dates: September 1994 to June 1996

Setting: outpatient, multicenter, national

Country: USA

Participants

Inclusion criteria: men with:

• 45 – 85 years old

• Symptomatic BPH confirmed by digital rectal examination (DRE) and transrectal ultrasound (TRUS)

• Qmax ≤ 12 mL/s with voided volume ≥ 125 mL on at least 2 clinic visits within 30 days of study enrollment

• AUA (American Urological Association) symptom score ≥ 9

• 3–5‐cm preprostatic urethral length as determined by cystoscopy or TRUS

• No disproportionately enlarged or prominent prostatic median lobe on cystoscopy

• Life expectancy ≥ 1 year

• Informed written consent

Exclusion criteria: men with:

• UTI within 1 week of study enrollment as diagnosed by positive urine culture

• Gross hematuria not due to BPH

• Acute urinary retention

• Prostate weight > 100 g

• Use of alpha‐antagonists within 4 wks or antiandrogens within 3 months of study enrollment

• Concomitant medications that could affect study outcome measures

• Co‐existing disease that could mimic obstructive bladder neck syndrome

• Co‐existing illness or specific obstructive symptoms caused by neurogenic bladder; bladder stones; renal failure; cardiac failure; prostate cancer; urethral stricture (i.e. inability to pass 22F urethroscope easily); severe bladder neck contracture; bladder cancer; urinary sphincter abnormalities; prostatitis; or hepatic failure

• Continuous or intermittent urinary catheterization within 2 weeks of the study procedure

• Previous prostate surgery or nonmedical treatment for BPH other than balloon dilation ≤ 12 mo before study entry

• Penile implant or artificial urinary sphincter

• Previous pelvic or rectal surgery that would increase participant risk or render study procedures more difficult

• Metallic implants in the pelvic area

• Cardiac pacemaker

• Desire for future offspring

• Likely noncompliance with study follow‐up evaluation requirements

Total number of participants randomized: 169

Group 1: n = 125 transurethral microwave thermotherapy (TUMT)

• Age, mean (95% CI): 66.0 (64.7 – 67.4) years.

• Prostate volume (cc), mean (95% CI): 38.1 (35.1 – 41.2)

• PSA (ng/mL), mean (95% CI): 3.4 (2.7 – 4.1)

• AUA score, Mean (95% CI): 20.8 (19.8 – 21.9)

• Qmax (mL/s), Mean (95% CI): 7.8 (7.4 – 8.2)

Group 2: n = 44 Sham

• Age, mean (95% CI): 65.9 (63.4 – 68.3) years.

• Prostate volume (cc), mean (95% CI): 44.7 (38.8 – 50.5)

• PSA (ng/mL), mean (95% CI): 3.6 (2.2 – 5.1)

• AUA score, Mean (95% CI): 21.3 (19.3 – 23.3)

• Qmax (mL/s), Mean (95% CI): 7.8 (7.00 – 8.6)

Interventions

Group 1 (n = 125): TUMT

Power was applied with a Targis device in increments to achieve a target urethral temperature of 40 ± 1 °C with measurement by the catheter’s fibreoptic thermo sensor. Microwave treatment was administered continuously for 1 hour, with the circulation of coolant at 8 °C

Group 2 (n = 44): Sham

The same procedure as TUMT group, with the exception that microwave power was not applied, and coolant temperature was increased in increments from 8 °C to 20 °C over the same time period as microwave power was increased in the microwave group. It was not feasible to increase the urethral temperature further in the sham group because the Targis cooling system is not designed or equipped to provide active heating of coolant other than that occurring as the result of the application of microwave energy. The sham‐group participants experienced rising urethral temperatures rather than unchanging low temperatures

Co‐interventions: All participants underwent insertion of a Targis (formerly T3) transurethral thermoablation system treatment catheter (Urologix, Inc., Minneapolis, Minn). It is a compact and portable unit equipped with a 21F silicone treatment catheter containing a helical dipole microwave antenna operating in the range 902 to 928 MHz. This provides urethral cooling via circumferential cooling compartments and also includes a urine drainage canal and a fibreoptic thermo sensor for monitoring urethral catheter interface temperatures. The thermoablation system automatically interrupts microwave power if urethral temperatures reach 44.5 °C or higher or rectal temperatures reach 42.5 °C or higher. Catheterization was carried out under topical lidocaine anesthesia. The positioning of the catheter balloon and antenna was confirmed by TRUS. The catheter was then secured in the proper spatial orientation with respect to the posteroanterior prostatic axis. A rectal thermal unit equipped with 5 thermocouples was used to monitor rectal temperatures. All participants received a 3‐day prescription of prophylactic oral antibiotics and catheterization for 36 to 60 hours

Outcomes

Urologic symptom scores

How measured: AUA score

Time points measured: baseline, 6 weeks, 3 months and 6 months

Time points reported: baseline, 6 weeks, 3 months and 6 months

Subgroups: none

Quality of life

How measured: QOL score was evaluated by participant responses to the question of how they would feel if their current urinary symptoms were to continue indefinitely.

Time points measured: Baseline and 6 months

Time points reported: baseline, 6, 9 and 12 months follow‐up (these last 2 time points were not reported In group 2)

Subgroups: none

Minor and major adverse event (including ejaculatory function)

How measured: number of participants with UTI confirmed by urine culture and resolved with antibiotics, among other adverse events

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Retreatment

How measured: number of participants requiring other treatment within the 6 months follow‐up

Time points measured: 6 months

Time points reported: 6 months

Subgroups: none

Acute urinary retention

How measured: number of participants with urinary retention > 1 week after the procedure

Time points measured: > 1 week

Time points reported: > 1 week

Subgroups: none

Relevant outcomes not reported in this study

• Erectile function

• Indwelling urinary catheter (all participants were catheterized)

Funding sources

This study was supported by a grant from Urologix Inc

Declarations of interest

Not available

Notes

Blinding was broken after 6 months (we included data from the blinded phase in this review).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: “Patients were randomised in a 3:1 target ratio to the microwave (n = 125) or sham (n = 44) group.”

Comment: Insufficient information about the sequence generation process to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: “Patients were randomised in a 3:1 target ratio to the microwave (n = 125) or sham (n = 44) group.”

Comment: Insufficient information about the sequence generation process to permit judgment of ‘Low risk’ or ‘High risk’.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: “The study was double‐blind: Neither the patients nor any of the investigators and support staff involved in carrying out the study procedures had knowledge of group assignment (microwave versus sham).”

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Quote: “The study was double‐blind: Neither the patients nor any of the investigators and support staff involved in carrying out the study procedures had knowledge of group assignment (microwave versus sham).”

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Quote: “The study was double‐blind: Neither the patients nor any of the investigators and support staff involved in carrying out the study procedures had knowledge of group assignment (microwave versus sham).”

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Quote: “Of the 169 patients enrolled, 155 were evaluable at the conclusion of the 6‐month blinded phase of the study (Table III) and 114 at the end of the full 12‐month follow‐up period. Analyses of efficacy results are presented for the 155 subjects evaluable at the conclusion of the blinded phase.”

Comment: Unbalanced attrition at 6 months (20% vs 4%).

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: prospective, randomized parallel study

Study dates: not reported

Setting: outpatient, single‐center, national

Country: United Kingdom

Participants

Inclusion criteria: men with:

• Symptoms of lower urinary tract dysfunction due to benign enlargement of the prostate meriting surgical treatment

• Qmax < 15 mL/s

• Voided volume ≥ 150 mL

• Maximum detrusor pressure ≥ 70 cmH2O

Exclusion criteria: men with:

• Complications of bladder outlet obstruction

• Urinary retention

• Residual urine volume > 350 mL

• Renal failure

• Recurrent urinary tract infection

• Bladder calculus

• Bladder diverticulum

• Suspicion of malignancy

• Clinical features suggestive of malignancy

• DRE suspicious of malignancy

• Abnormal PSA level

• Short prostate (< 30 mm on TRUS)

• Presence of a prominent middle lobe projecting asymmetrically into the bladder

• Presence of a urethral stricture

• Previous prostate or pelvic surgery or radiotherapy

• Presence of metal within the lower trunk or upper legs

• Uncontrolled cardiac dysrhythmias or presence of a cardiac pacemaker

• Presence of neurological disorders that might affect the lower body

• Inability to understand the investigations, treatment procedure or give fully‐informed consent

• Presence of other treatment/medication which might affect lower urinary tract function

Total number of participants randomized: 120

Age, median (range): 70 (56 ‐ 80) years (no disaggregated data by group available)

Group 1: n = 38 transurethral microwave thermotherapy (TUMT)

AUA score, median (range): 19 (7 ‐ 31)

Qmax, mean (SD): 8.83 (2.32) mL/s

Prostate volume, mean (SD): 41.2 (14.6) mL

Group 2: n = 40 sham transurethral microwave thermotherapy (TUMT)

AUA score, median (range): 17.5 (7 ‐ 28)

Qmax, mean (SD): 9.44 (2.78) mL/s

Prostate volume, mean (SD): 46.7 (16.8) mL

Group 3: n = 42 no treatment

AUA score, median (range): 18 (10 ‐ 29)

Qmax, mean (SD): 8.79 (2.66) mL/s

Prostate volume, mean (SD): 46.4 (19.9) mL

Interventions

Group 1 (n = 38): TUMT

It was delivered for an hour under local anesthesia, through a urethral catheter using Prostatron. The temperature was measured through the catheter and a rectal probe and guided the cooling of the urethra through a software (Prostasoft v2.0) which was not under the control of the operator

Group 2 (n = 40): Sham

A technically identical procedure to standard TUMT with no microwaves, with similar noise and appearance with simulated heat using a heat pad

Group 3 (n = 42): No treatment (they received treatment after completion of the study)

Co‐interventions: not reported

Outcomes

Urologic symptom scores

How measured: AUA score

Time points measured: baseline and 6 months

Time points reported: baseline and 6 months

Subgroups: none

Major and minor adverse events

How measured: not reported

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Acute urinary retention

How measured: number of participants developing acute urinary retention in the first 24 hrs after treatment

Time points measured: not reported

Time points reported: not reported

Subgroups: none

Relevant outcomes not reported in this study

• Quality of life

• Retreatment

• Erectile function

• Ejaculatory function

• Indwelling urinary catheter

Funding sources

LORS grant from the South East Thames Regional Research Committee

Declarations of interest

Not available

Notes

We included that TUMT and sham arms of the study in our review.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Comment: The investigators describe a random component in the sequence generation process.

Quote: “Randomization was carried out by selecting one of three differently numbered but otherwise identical balls from a sealed bag.”

Allocation concealment (selection bias)

High risk

Comment: The allocation could be tampered with, considering that the balls could be re‐inserted to the bag and pulled out again.

Quote: “Randomization was carried out by selecting one of three differently numbered but otherwise identical balls from a sealed bag.”

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

Quote: “The treatment of the standard and simulated TUMT groups was designed and carried out as a double‐blind, so that neither the operator nor the patient was aware of which treatment was being per‐ formed. Patients randomised to group 3 were treated after completion of the study.”

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All outcomes: No apparent missing outcome data.

Selective reporting (reporting bias)

Unclear risk

No protocol available. There is a trial registry (ISRCTN24866285), but it was retrospectively registered and there is no information about the outcomes.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: prospective, randomized stud.

Study dates: May 1996 and November 1999

Setting: outpatient, multicenter, national

Country: Denmark

Participants

Inclusion criteria: symptomatic benign prostatic hyperplasia (BPH) and:

• Age ≥ 50 years

• IPSS ≥ 7

• QoL ≥ 3

• Obstructed according to ICS nomogram or Qmax (free uroflowmetry) < 12 mL/s

• Able to understand project information

• Written consent

Exclusion criteria: men with:

• Suspicion of prostate cancer

• Postvoid residual volume (PVR) > 350 mL or urinary catheter

• Prostatic urethra < 25 mm long

• Neurological diseases or diabetes with abnormal cystometry

• Previous prostate operation

• Ongoing UTI Previous diagnosis of rectal cancer

• Intake of medication known to influence voiding

• Severe peripheral arterial insufficiency

• Previous pelvic radiation therapy

• General health condition contraindicating surgery

Total number of participants randomized: 118

Group 1: 48 Interstitial laser coagulation (ILC)

• Age, mean (SD): 65 (8) years

• Serum creatinine, mean (SD): 97 (13) umol/L

• Median prostate volume, Median (IQR): 44 (33 – 58) mL

• PSA, Median (IQR): 2.3 (1.7 – 6.3) ng/mL

• Qmax, mean (SD): 10.2 (4.0) mL/s

Group 2: 46 transurethral microwave thermotherapy (TUMT)

• Age, mean (SD): 66 (7) years

• Serum creatinine, mean (SD): 99 (13) umol/L

• Median prostate volume, Median (IQR): 43 (35 – 79) mL

• PSA, Median (IQR): 3.3 (1.4 – 5.7) ng/mL

• Qmax, mean (SD): 9.1 (4.2) mL/s

Group 3: 24 (control: TURP or TUIP)

• Age, mean (SD): 68 (7) years

• Serum creatinine, mean (SD): 99 (20) umol/L

• Median prostate volume, Median (IQR): 44 (35 – 50)mL

• PSA, Median (IQR): 2.2 (1.5 – 4.1) ng/mL

• Qmax, mean (SD): 9.6 (3.2)mL/s

Interventions

Group 1 (n = 48): “ILC was delivered by a MediLas 4100 Fibertom (Dornier, Germany), a Nd‐YAG laser with a wavelength of 1064 nm. The energy was delivered using an applicator with a quartz glass tip (length 20 mm, diameter 1.9 mm). The 3‐min radiation was used, thus applying 20 W for 30 s, 15 W for 30 s, 10 W for 30 s and 7 W for 90 s. Treatments were undertaken with a laser cystoscope (18 F) using saline as the irrigant. The fibre was placed deep within the lateral lobes at an angle in the plane of the urethra of 30º (to avoid heating the urethral mucosa). If a median lobe was present it was treated with one or two punctures in the direction of the bladder. Initially the intent was to apply one puncture per 10 mL of prostate tissue, but later the regimen became more aggressive, aiming at one puncture per 5 mL. All patients had a suprapubic tube placed at the start of the procedure and most also had a transurethral catheter for 12–24 h to reduce prostatic oedema. All patients received prophylactic antibiotics. Patients were discharged after removing the urethral catheter and scheduled to visit the outpatient clinic for removal of the suprapubic tube, generally at fixed intervals of 1–2 weeks.”

Group 2 (n = 46): “TUMT was administered using the Prostatron® system; before treatment cystoscopy was used to exclude bladder pathology. Prostasoft v2.0 was chosen when the prostatic volume was < 30 mL and v2.5 in larger prostates. Treatment comprised 1 h sessions under local anaesthesia with Installagel® (Farco‐Pharma GmbH, Cologne, Germany); 1 h beforehand, 100 mg of diclofenac and 500 mg ciprofloxacin was administered. During treatment pethidine was given if necessary. If patients developed urinary retention after treatment a suprapubic or a transurethral catheter was inserted and the patient seen at weekly intervals until spontaneous voiding with an acceptable PVR (in general < 100 mL) was achieved.”

Group 3 (n = 24): “Patients underwent TUIP or TURP according to the surgeons’ decision. The prostate was resected using a 26 F Iglesias resectoscope with a standard resection loop and 1.5% glycine for irrigation. TUIP comprised a unilateral incision in the 7 o’clock position starting proximal to the bladder neck and extending distally to the verumontanum. After surgery a three‐way irrigation catheter was inserted and first removed when bleeding had stopped. Prophylactic antibiotics were given according to the routine of the department.”

Co‐interventions: “All treatments were administered by one of the two consultants or the senior registrar. Patients were treated under spinal or general anaesthesia.”

Outcomes

Urologic symptom scores

How measured: IPSS

Time points measured: baseline, 1, 3 and 6 months

Time points reported: baseline and 6 months

Subgroups: none

Quality of life

How measured: not reported

Time points measured: baseline, 1, 3 and 6 months

Time points reported: baseline and 6 months

Subgroups: none

Major and minor adverse event

How measured: number of participants with bleeding necessitating transfusion

Time points measured: 6 months

Time points reported: 6 months

Subgroups: none

Retreatment

How measured: number of participants undergoing TURP or other treatment

Time points measured: 6 months

Time points reported: 6 months

Subgroups: none

Erectile function

How measured: To evaluate erectile function participants scoring 0 or 1 (i.e. normal or slightly reduced erectile capacity) were defined as ‘normal’, whereas participants scoring 2 or 3 (i.e. greatly reduced or no erectile function) were defined having decreased erectile capacity

Time points measured: 6 months

Time points reported: 6 months

Subgroups: none

Ejaculatory function

How measured: number of patients with retrograde ejaculation

Time points measured: 6 months

Time points reported: 6 months

Subgroups: none

Acute urinary retention

How measured: number of participants with persistent retention after treatment

Time points measured: 6 months

Time points reported: 6 months

Subgroups: none

Indwelling urinary catheter

How measured: not reported

Time points measured: 6 months

Time points reported: 6 months (narratively)

Subgroups: none

Funding sources

The study was supported by a grant from Vejle County, Denmark

Declarations of interest

Not available

Notes

ILC group data are not included in this review.

Antibiotic regimen in ILC group was changed during the study because there was a high rate of UTI.

“The study had to be stopped at the final date because of financial restrictions.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: 2:1:1: Randomization ‐ “A weighted randomisation was therefore chosen as the object was to gain maximum information about the new treatments.”

Comment: Insufficient information about the sequence generation process to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Quote: “Patients were recruited from two centres and randomised at a 2:2:1 to TUMT, ILC or the control group.”

Comment: Method of allocation concealment is not described in sufficient detail to allow a definite judgment

Blinding of participants and personnel (performance bias)
All outcomes

High risk

No blinding.

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

No blinding, but the outcomes ar not likely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

High risk

No blinding, and the outcomes are likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: “Analyses are presented on an intention‐to‐treat basis.” 

Group 1: “Before ILC but after randomisation two patients had prostate cancer diagnosed and one had a urethral stricture. A further two patients declined surgery. One of these patients completed the IPSS at 6 months by mail contact. Thus, 44 patients were available for evaluation at 6 months.”

Group 2: “All patients were followed at 6 months except one who developed an apoplexy at 4 months. One patient had TURP.”

Group 3: “23 of 24 patients were treated according to the randomisation. One patient declined surgery. Two patients were excluded as the pathology revealed T1 prostate cancer.”  

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

The study appears to be free of other sources of bias.

Study characteristics

Methods

Study design: prospective, randomized study

Study dates: not reported

Setting: outpatient, multicenter centre, national

Country: USA

Participants

Inclusion criteria: men with:

• Age ≥ 55 years

• Score 13 points or more on the American Urological Association symptom index (AUA SI)

• 2 subsequent flow rates with peak urinary flow rate of 12 mL/s or less

• Voided volume > 125 mL.

• Serum prostate‐specific antigen (PSA) had to be < 10 ng/mL (monoclonal assay)

• Prostate volume between 25 and 100 mL

• Bladder neck to verumontanum distance > 30 mm

• Written informed consent

Exclusion criteria: not reported

Total number of participants randomized: 220

Group 1 (n = 147) TUMT

• Age, mean (SD): 66.3 (6.5) years

• AUA SI (0 – 35), mean (SD): 23.6 (5.6)

• AUA PI (0 – 28), mean (SD): 18.6 (5.8)

• BPH II (0 – 13), mean (SD): 7.2 (2.7)

• QOL score (0 – 6), mean (SD): 4.3 (1.0)

• Voided volume, mean (SD): 254 (82) mL

• Residual urine, mean (SD): 79.7 (70.1) mL

• PSA, Mean (SD): 3.1 (2.7) ng/mL

• PFR, mean (SD): 7.7 (2.0) mL/s

• Prostate volume, mean (SD): 48.1 (16.2) mL

Group 2 (n = 73) Sham

• Age, mean (SD): 66 (5.8) years

• AUA SI (0 – 35), mean (SD): 23.9 (5.6)

• AUA PI (0 – 28), mean (SD): 18.6 (6.0)

• BPH II (0 – 13), mean (SD): 7.3 (3.1)

• QOL score (0 – 6), mean (SD): 4.3 (1.1)

• Voided volume, mean (SD): 251 (92) mL

• Residual urine, mean (SD): 67.5 (64.4) mL

• PSA, Mean (SD): 2.8 (2.0) ng/mL

• PFR, mean (SD): 8.1 (2.0) mL/s

• Prostate volume, mean (SD): 50.5 (18.1) mL

Interventions

Group 1 (n = 147) TUMT

The Dornier Urowave (second‐generation microwave therapy device), can deliver up to 90 W of power and has an integrated water‐cooling circuit. The safety threshold was set at 50 °C in the urethra and at 42.5 °C in the rectum

Group 2 (n = 73) Sham: sham‐treated participants received a 60‐minute, preprogrammed sham treatment cycle with the catheter in place

Co‐interventions: All participants had negative urine cultures before treatment and were given peritreatment antibiotic prophylaxis (investigators’ choice). After treatment, an indwelling Foley catheter was inserted and left in place for 2 to 5 days, depending on logistics

Outcomes

Urologic symptom scores

How measured: AUA‐SI (0 to 35 points)

Time points measured: baseline, 1, 3, and 6 months

Time points reported: baseline, 1, 3, and 6 months

Subgroups: none

Quality of Life

How measured: AUA‐SI subscore (0 to 6 points)

Time points measured: baseline, 1, 3, and 6 months

Time points reported: baseline, 1, 3, and 6 months

Subgroups: none

Major and minor adverse events (including ejaculatory and erectile function)

How measured: Adverse events were solicited from participants during and after treatment as well as at each follow‐up visit. Adverse events were designated as treatment‐related or unrelated to treatment by the investigator

Time points measured: during treatment, 72 hrs after treatment and up to 6 months

Time points reported: during treatment, 72 hrs after treatment and up to 6 months

Subgroups: none

Acute urinary retention

How measured: not reported

Time points measured: baseline, 1, 3, and 6 months

Time points reported: 6 months

Subgroups: none

Relevant outcomes not reported in this study

• Retreatment

• Indwelling urinary catheter: not applicable since “an indwelling Foley catheter was inserted and left in place for 2 to 5 days, depending on logistics” (all participants).

Funding sources

Funded by Dornier MedTech, Atlanta, Georgia

Declarations of interest

Not available

Notes

A secondary report states that quality of life was also measured by another scale (0 ‐ 21), but it is not clear which scale was used.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Comment: The investigators describe a random component in the sequence generation process.

Quote: “The physician administering the treatment opened the centrally provided randomisation envelope immediately before treatment.”

Allocation concealment (selection bias)

Low risk

Comment: Participants and investigators enrolling participants could not foresee assignment.

Quote: “The physician administering the treatment opened the centrally provided randomisation envelope immediately before treatment.”

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Comment: Blinding of participants and key study personnel was ensured, and it was unlikely that the blinding could have been broken.

Quote: “They were made aware that in this trial there would be an active/sham randomizations at a ratio of 2:1. Furthermore, patients were made aware that a ‘‘subset’’ of patients would have interstitial temperature monitoring by way of inserting a needle through the perineum into the prostate. However, for ethical reasons, only actively treated patients received such monitoring. Thus, the patients were effectively blinded as to whether or not they underwent active or sham treatment despite the fact that only the actively treated patients had interstitial temperature monitoring.”

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Comment: Blinding of participants and key study personnel was ensured, and it was unlikely that the blinding could have been broken.

Quote: “The treating physician and assistant were excluded from the follow‐up evaluation of the patient. The physician and/or nurse involved in the follow‐up evaluation was not present in the room during treatment.”

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Comment: Blinding of participants and key study personnel was ensured, and it was unlikely that the blinding could have been broken.

Quote: “The treating physician and assistant were excluded from the follow‐up evaluation of the patient. The physician and/or nurse involved in the follow‐up evaluation was not present in the room during treatment.”

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Comment: Insufficient reporting of attrition/exclusions to permit judgment of ‘Low risk’ or ‘High risk'.

Quote: “For the various parameters, between 124 and 130 of the actively treated patients (86% to 88%) were available for 6‐month follow‐up; in the sham‐treated group, between 65 and 67 (89% to 92%) of patients were available for 6‐month follow‐up.”

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.

Study characteristics

Methods

Study design: prospective, randomized study

Study dates: not reported

Setting: outpatient, multicenter, national

Country: United Kingdom

Participants

Inclusion criteria: men with:

• Madsen score > 8

• Urodynamic evidence of BOO

• Residual urine volumes < 250 mL

• Predominantly lateral lobe enlargement

• No evidence of prostate or bladder cancer

• No previous surgery on the lower urinary tract

Exclusion criteria: not reported

Total number of participants randomized: 96

Group 1: n = 48 Transurethral microwave Hyperthermia

• Age (years) 70.5

• Madsen score 12.7

• AUA score 19.2

• AUA bothersome score 11

• Urinary flow rate (mL/s) 11.5

• Prostatic volume (cm³) 40.4

* no SD or 95% CI reported

Group 2: n = 48 transurethral sham

• Age (years) 68

• Madsen score 13

• AUA score 20.1

• AUA bothersome score 12.3

• Urinary flow rate (mL/s) 10.2

• Prostatic volume (cm³) 40.6

* no SD or 95% CI reported

Interventions

Group 1 (n = 48) TUMT

Participants in the treated group underwent 1 hr of microwave hyperthermia, with a maximum urethral temperature of 46 °C or a maximum rectal temperature of 42.5 °C. The machine was designed and constructed in conjunction with Microwave Engineering Designs, Newport, Isle of Wight, UK (434 MHz, maximum power of 50 W). The antenna was a helical coil, loaded in a modified eyeless 22F Foley Simplastic catheter fitted with water cooling

Group 2 (n = 48) Sham

Treated with the same procedure but without the use of heat

Co‐interventions:

After selection for inclusion in the trial a treatment catheter was inserted under antibiotic cover (gentamicin 80 mg)

Outcomes

Urologic symptom scores

How measured: AUA scores (percentage of improvement). Madsen score response rate (responders as those with a score < 8)

Time points measured: baseline,3 and 6 months

Time points reported: baseline,3 and 6 months (responder data only at 3 months)

Subgroups: none

Relevant outcomes not reported in this study

• Quality of life (measured for multivariate analysis but not reported)

• Retreatment

• Ejaculatory function

• Erectile function

• Major and minor adverse events

• Acute urinary retention

• Indwelling urinary catheter

Funding sources

Not available

Declarations of interest

Not available

Notes

Participants were selected from waiting lists for transurethral resection of the prostate (TURP) at St Thomas's Hospital and Worthing Hospital, or by direct referral.

Cross‐over: after 3 months, 47 participants in the treated group and 46 of the controls were assessed. After 6 months, 42 treated participants and 20 control participants were assessed, because 24 participants in the control group had been made aware of the sham treatment and so were not included in the analysis

Protocol: not available

Language of publication: English

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Comment: The investigators describe a random component in the sequence generation process.

Quote: “patients were then randomly assigned to either a treated or control group by selection of sealed envelopes prepared before the trial.”

Allocation concealment (selection bias)

Unclear risk

Comment: Participants and investigators enrolling participants could not foresee assignment, although it is not clear if the envelopes were opaque.

Quote: “patients were then randomly assigned to either a treated or control group by selection of sealed envelopes prepared before the trial.”

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Comment: It is unclear if personnel was blinded (first 3 months).

Quote: “The patients were not aware of the group to which they were assigned.”

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

Comment: These outcomes are unlikely to be affected by blinding.

Quote: “The patients were not aware of the group to which they were assigned.”

Blinding of outcome assessment (detection bias)
Subjective outcomes

Low risk

Comment: These outcomes are likely to be affected by blinding.

Quote: “The patients were not aware of the group to which they were assigned.”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All outcomes: outcome data was available for nearly all participants. After 3 months, 47/48 patients in the treated group and 46/48 of the controls were assessed (6‐month data not included in this review, see “Notes”)

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified

Study characteristics

Methods

Study design: prospective, randomized study

Study dates: October 1998 to November 1999

Setting: outpatient, multicenter, international

Country: Scandinavia and USA

Participants

Inclusion criteria: men with:

• Symptomatic BPH

• International Prostate Symptom Score (IPSS) of 13 or greater

• Prostate volume of 30 to 100 mL

• Peak urinary flow rate (Qmax) < 13 mL/s

Exclusion criteria: not reported

Total number of participants randomized: 154

Group 1: n = 103 Microwave Treatment

• Age, mean (SD): 67 (8) years

• Weight, mean (SD): 83 (15) kg

• Height, mean (SD): 178 (6) cm

• Residual urine volume, mean (SD): 106 (77) mL

• Detrusor (voiding) pressure, mean (SD): 73.7 (29.7) cm H2O

• Maximal free urinary flow rate, mean (SD): 7.6 (2.7) mL/s

• PSA, mean (SD): 3.3 (2.2) g/L

• Prostate volume as determined by TRUS, mean (SD): 48.9 (15.8) cm³

• IPSS, mean (SD): 21.0 (5.4)

• Bother score, mean (SD): 4.3 (1.0)

Group 2: n = 51 Transurethral resection of the prostate

• Age, mean (SD): 69 (8) years

• Weight, mean (SD): 81 (11) kg

• Height, mean (SD): 177 (6) cm

• Residual urine volume, mean (SD): 94 (82) mL

• Detrusor (voiding) pressure, mean (SD): 79.4 (35.3) cm H2O

• Maximal free urinary flow rate, mean (SD): 7.9 (2.7) mL/s

• PSA, mean (SD): 3.6 (2.7) g/L

• Prostate volume as determined by TRUS, mean (SD): 52.7 (17.3) cm³

• IPSS, mean (SD): 20.4 (5.9)

• Bother score, mean (SD): 4.2 (1.1)

Interventions

Group 1 (n = 103) TUMT

ProstaLund feedback measured temperatures and were continuously displayed on the device computer. Using the heat equation, the device also calculates the extent of the coagulation necrosis continuously during the treatment, stopping at 55 °C

Group 2 (n = 51): TURP

TURP was performed as a clinical standard inpatient procedure according to the routines at each centre

Co‐interventions: A washout period of at least 6 weeks preceded the treatment for participants who had been using any alpha‐receptor blocker or finasteride

Outcomes

Urologic symptom scores

How measured: IPSS
Time points measured: baseline, 3, 6, 12, 24, 36, 48 and 60 months

Time points reported: baseline, 3, 6, 12, 24, 36, 48 and 60 months

Subgroups: none

Quality of life

How measured: QoL domain of IPSS score

Time points measured: baseline, 3, 6, 12, 24, 36, 48 and 60 months

Time points reported: baseline, 3, 6, 12, 24, 36, 48 and 60 months

Subgroups: none

Major adverse events

How measured: All adverse events occurring during the entire study period were reported. A serious adverse event was defined according to International Congress on Harmonization as any untoward medical event that resulted in death, was life‐threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was cancer, or required intervention to prevent permanent damage to body functions or structure

Time points measured: during treatment and up to 12 months

Time points reported: during treatment and up to 12 months

Subgroups: none

Minor adverse events (includes acute urinary retention and erectile dysfunction)

How measured: not reported

Time points measured: during treatment or up to 12 months, and from 12 to 60 months

Time points reported: during treatment or up to 12 months, and from 12 to 60 months

Subgroups: none

Indwelling urinary catheter

How measured: time with the catheter

Time points measured: after the procedure

Time points reported: after the procedure

Subgroups: none

Retreatment

How measured: number of participants with additional medical or surgical treatment

Time points measured: after the procedure

Time points reported: after the procedure

Subgroups: none

Relevant outcomes not reported in this study

• Ejaculatory dysfunction

Funding sources

Funded by ProstaLund.

Declarations of interest

Wagrell L, Schelin S, Larson TR, and Mattiasson A were paid consultants to the sponsor of this study.

Notes

A total of 154 participants were included on an intention‐to‐treat basis. Eight participants (5 in the TURP and 3 in the PLFT group) were withdrawn before treatment, resulting in a total of 146 treated participants; 100 in the PLFT arm and 46 in the TURP arm.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Insufficient information about the sequence generation process to permit judgment of ‘Low risk’ or ‘High risk’.

Allocation concealment (selection bias)

Unclear risk

Comment: Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Quote: “The randomisation ratio between PLFT and TURP was 2:1.”

Blinding of participants and personnel (performance bias)
All outcomes

High risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

Blinding of outcome assessment (detection bias)
Objective outcomes

Low risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

The objective outcomes were unlikely to be influenced by lack of blinding.

Blinding of outcome assessment (detection bias)
Subjective outcomes

High risk

While blinding was not mentioned, the interventions were visibly different (surgery versus outpatient procedure).

The subjective outcomes were likely to be influenced by lack of blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

12 months: balanced attrition, and outcome data were available for 133/154 (86%)

Judgment: low risk of bias

24 months: outcome data was available for 79/103 in the TUMT group and 39/51 in the TURP group (76%)

36 months: outcome data was available for 69/103 in the TUMT group and 35/51 in the TURP group

60 months: outcome data was available for 62/103 in the TUMT group and 34/51 in the TURP group

Judgment: high risk of bias

Selective reporting (reporting bias)

Unclear risk

No protocol available. Insufficient information to permit judgment of ‘Low risk’ or ‘High risk’.

Other bias

Low risk

No other sources of bias were identified.