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Intermittent versus continuous androgen suppression for prostatic cancer

Abstract

Background

After lung cancer, prostate cancer is the most common cause of death among males. The aim of treatment is to prevent disease‐related morbidity and mortality while minimizing intervention‐related adverse events. Androgen suppression therapy (AST) to reduce circulating serum testosterone and disease progression is considered a mainstay of treatment for men with advanced prostate cancer. It has been increasingly utilized for early stage disease despite a lack of evidence of effectiveness.

Objectives

Evaluate the effectiveness and safety of intermittent androgen suppression (IAS) compared to continuous androgen suppression for treating prostatic cancer.

Search methods

The following databases were searched to identify randomised or quasi‐randomised, controlled trials comparing intermittent and continuous androgen suppression in the treatment of any stage of prostate cancer: the Cochrane Central Register of Controlled Trials; EMBASE and LILACS.

Selection criteria

Studies were included if they were randomised or quasi‐randomized, and compare the effects of IAS versus CAS.

Data collection and analysis

Two reviewers selected relevant trials, assessed methodological quality and extracted data.

Main results

Five randomized studies involving 1382 patients were included in this review. All the included studies involved advanced (T3 or T4) prostate cancer, had relatively small populations, and were of short duration. Few events were reported and did not assess disease‐specific survival or metastatic disease. Only one study (N = 77) evaluated biochemical outcomes. A subgroup analysis found no significant differences in biochemical progression (defined by the authors as PSA ≥ 10 ng/mL) between IAS and CAS for Gleason scores 4 ‐ 6, 7, and 8 ‐ 10. For patients with a Gleason score > 6, reduction in biochemical progression favoured the IAS group (RR 0.10, 95% CI 0.01 to 0.67, P = 0.02). Studies primarily reported on adverse events. One trial (N = 43) found no difference in adverse effects (gastrointestinal, gynecomastia and asthenia) between IAS ( two events) and CAS (five events), with the exception of impotence, which was significantly lower in the IAS group (RR 0.72, 95% CI 0.56 to 0.92, P = 0.008).

Authors' conclusions

Data from RCTs comparing IAS to CAS are limited by small sample size and short duration. There are no data for the relative effectiveness of IAS versus CAS for overall survival, prostate cancer‐specific survival, or disease progression. Limited information suggests IAS may have slightly reduced adverse events. Overall, IAS was also as effective as CAS for potency, but was superior during the interval of cycles (96%).

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

available in

To evaluate the effectiveness and safety of intermittent androgen suppression compared to continuous androgen suppression for treating prostatic cancer.

After lung cancer, prostate cancer is the most common cause of death among males. The American Cancer Society estimates that 234,460 new cases of prostate cancer were diagnosed, and 27,350 men died from this disease in the United States in 2006 (ACS 2006). Treatment for early stage prostate cancer that is believed to be confined to the prostate gland include: radical prostatectomy, external beam or interstitial radiation therapy, and watchful waiting. Androgen suppression therapy (AST) to reduce circulating serum testosterone and disease progression is considered a mainstay of treatment for men with advanced prostate cancer.

Five studies involving 1382 patients were included in this review. All the included studies involved advanced (T3 or T4) prostate cancer. No study was of adequate size and duration. Few events were reported and they did not assess disease‐specific survival or metastatic disease. Only one study evaluated biochemical outcomes. Studies primarily reported on adverse events. There are no data for the relative effectiveness of IAS versus CAS for overall survival, prostate cancer specific survival, disease progression, or quality of life. Limited information suggests IAS may have slightly reduced adverse events. In Hering 2000, IAS (18/25 versus 18/18) appears to be slightly more favorable than CAS in controlling impotence. Overall, IAS was also as effective as CAS for potency, but was superior during the interval of cycles (96%). More research is needed.