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Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 1 Overall survival.
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Analysis 1.1

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 1 Overall survival.

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 2 Disease‐free survival at 5 years (intention‐to‐treat analysis).
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Analysis 1.2

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 2 Disease‐free survival at 5 years (intention‐to‐treat analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 3 pT Staging: Organ Confined (Intention‐to‐treat Analysis).
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Analysis 1.3

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 3 pT Staging: Organ Confined (Intention‐to‐treat Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 4 pT Staging: Organ Confined (Case Analysis).
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Analysis 1.4

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 4 pT Staging: Organ Confined (Case Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 5 pT Staging: Downstaging (Intention‐to‐treat Analysis).
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Analysis 1.5

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 5 pT Staging: Downstaging (Intention‐to‐treat Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 6 pT Staging: Downstaging (Case Analysis).
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Analysis 1.6

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 6 pT Staging: Downstaging (Case Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 7 Positive Surgical Margin Status (Intention‐to‐treat Analysis).
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Analysis 1.7

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 7 Positive Surgical Margin Status (Intention‐to‐treat Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 8 Positive Surgical Margin Status (Case Analysis).
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Analysis 1.8

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 8 Positive Surgical Margin Status (Case Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 9 Seminal Vesicle Invasion Rate (Intention‐to‐treat Analysis).
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Analysis 1.9

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 9 Seminal Vesicle Invasion Rate (Intention‐to‐treat Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 10 Seminal Vesicle Invasion Rate (Case Analysis).
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Analysis 1.10

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 10 Seminal Vesicle Invasion Rate (Case Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 11 Positive Lymph Nodes (Intention‐to‐treat Analysis).
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Analysis 1.11

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 11 Positive Lymph Nodes (Intention‐to‐treat Analysis).

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 12 Positive Lymph Nodes (Case Analysis).
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Analysis 1.12

Comparison 1 Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone, Outcome 12 Positive Lymph Nodes (Case Analysis).

Comparison 2 Short‐term versus Long‐term Neo‐adjuvant hormone therapy and prostatectomy, Outcome 1 Positive Surgical Margin Status (Case analysis only).
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Analysis 2.1

Comparison 2 Short‐term versus Long‐term Neo‐adjuvant hormone therapy and prostatectomy, Outcome 1 Positive Surgical Margin Status (Case analysis only).

Comparison 2 Short‐term versus Long‐term Neo‐adjuvant hormone therapy and prostatectomy, Outcome 2 pT Staging: Organ confined (Case analysis only).
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Analysis 2.2

Comparison 2 Short‐term versus Long‐term Neo‐adjuvant hormone therapy and prostatectomy, Outcome 2 pT Staging: Organ confined (Case analysis only).

Comparison 3 Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 1 Disease‐specific survival.
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Analysis 3.1

Comparison 3 Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 1 Disease‐specific survival.

Comparison 3 Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 2 Biochemical disease‐free survival.
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Analysis 3.2

Comparison 3 Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 2 Biochemical disease‐free survival.

Comparison 3 Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 3 Clinical disease‐free survival.
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Analysis 3.3

Comparison 3 Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 3 Clinical disease‐free survival.

Comparison 4 Short‐term versus long‐term neo‐adjuvant hormone therapy Radiotherapy, Outcome 1 3 year biochemical disease‐free survival.
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Analysis 4.1

Comparison 4 Short‐term versus long‐term neo‐adjuvant hormone therapy Radiotherapy, Outcome 1 3 year biochemical disease‐free survival.

Comparison 4 Short‐term versus long‐term neo‐adjuvant hormone therapy Radiotherapy, Outcome 2 5‐year biochemical disease free survival.
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Analysis 4.2

Comparison 4 Short‐term versus long‐term neo‐adjuvant hormone therapy Radiotherapy, Outcome 2 5‐year biochemical disease free survival.

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 1 Overall Survival: 5 Years.
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Analysis 5.1

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 1 Overall Survival: 5 Years.

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 2 Overall Survival: 10 Years.
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Analysis 5.2

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 2 Overall Survival: 10 Years.

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 3 Disease‐Free Survival: 5 Years.
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Analysis 5.3

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 3 Disease‐Free Survival: 5 Years.

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 4 Disease‐Free Survival: 10 Years.
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Analysis 5.4

Comparison 5 Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone, Outcome 4 Disease‐Free Survival: 10 Years.

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 1 Overall Survival: 5 Years.
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Analysis 6.1

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 1 Overall Survival: 5 Years.

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 2 Overall Survival: 10 Years.
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Analysis 6.2

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 2 Overall Survival: 10 Years.

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 3 Disease‐Specific Survival: 5 Years.
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Analysis 6.3

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 3 Disease‐Specific Survival: 5 Years.

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 4 Disease‐Free Survival: 10 Years.
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Analysis 6.4

Comparison 6 Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone, Outcome 4 Disease‐Free Survival: 10 Years.

Table 1. Definition of outcomes used in this review

Outcomes

Definition

Time‐to‐progression

A measure of the time after a disease is treated until the disease starts to get worse

Progression‐Free Survival

The probability that a patient will remain alive, without the disease getting worse

Disease progression

Cancer that continues to grow or spread

Overall Survival

Percentage of subjects in a study who have survived for a defined period of time. A.K.A. Survival rate.

Recurrence (Disease Recurrence/ Relapse)

Cancer that has returned after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumour or to another place in the body.

Disease‐Free Survival

Length of time after treatment during which no cancer is found

Disease‐Specific Survival

The percentage of subjects in a study who have survived a particular disease for a defined period of time. In calculating the percentage, only deaths from the disease being studied are counted

Surgical Margins

Surgical removal of a tumor with an additional margin of normal tissue, and the outer edge is coated with ink.

Positive (+) Surgical Margins

Cancer cells that are in contact with the inked outer surface (margin) are described as positive.

Negative (‐) Surgical Margins

Cancer cells not found at the edge of the inked tissue (Margin) are described as negative

Pathological (pT) Staging

The staging of cancer cells determined by tissue sample removed during surgery or a biopsy.

Seminal Vesicle Rate

The proportion of patients that have tumour infiltrating the seminal vesicles.

Positive Lymph Nodes

Tumour has spread to the lymph nodes ‐ generally the pelvic lymph nodes in prostate cancer.

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Table 1. Definition of outcomes used in this review
Comparison 1. Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall survival Show forest plot

3

827

Odds Ratio (M‐H, Fixed, 95% CI)

1.11 [0.67, 1.85]

2 Disease‐free survival at 5 years (intention‐to‐treat analysis) Show forest plot

4

1129

Odds Ratio (M‐H, Fixed, 95% CI)

1.20 [0.95, 1.52]

3 pT Staging: Organ Confined (Intention‐to‐treat Analysis) Show forest plot

4

922

Odds Ratio (M‐H, Fixed, 95% CI)

2.30 [1.72, 3.08]

4 pT Staging: Organ Confined (Case Analysis) Show forest plot

4

811

Odds Ratio (M‐H, Fixed, 95% CI)

2.61 [1.93, 3.53]

5 pT Staging: Downstaging (Intention‐to‐treat Analysis) Show forest plot

2

648

Odds Ratio (M‐H, Fixed, 95% CI)

2.42 [1.50, 3.90]

6 pT Staging: Downstaging (Case Analysis) Show forest plot

2

563

Odds Ratio (M‐H, Fixed, 95% CI)

2.60 [1.61, 4.21]

7 Positive Surgical Margin Status (Intention‐to‐treat Analysis) Show forest plot

8

1802

Odds Ratio (M‐H, Fixed, 95% CI)

0.34 [0.27, 0.42]

8 Positive Surgical Margin Status (Case Analysis) Show forest plot

8

1600

Odds Ratio (M‐H, Fixed, 95% CI)

0.32 [0.26, 0.40]

9 Seminal Vesicle Invasion Rate (Intention‐to‐treat Analysis) Show forest plot

2

516

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.70, 1.73]

10 Seminal Vesicle Invasion Rate (Case Analysis) Show forest plot

2

467

Odds Ratio (M‐H, Fixed, 95% CI)

1.09 [0.69, 1.71]

11 Positive Lymph Nodes (Intention‐to‐treat Analysis) Show forest plot

5

1247

Odds Ratio (M‐H, Fixed, 95% CI)

0.63 [0.43, 0.93]

12 Positive Lymph Nodes (Case Analysis) Show forest plot

5

1070

Odds Ratio (M‐H, Fixed, 95% CI)

0.67 [0.45, 1.00]

Figures and Tables -
Comparison 1. Neo‐adjuvant hormone therapy and Prostatectomy Versus Prostatectomy alone
Comparison 2. Short‐term versus Long‐term Neo‐adjuvant hormone therapy and prostatectomy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Positive Surgical Margin Status (Case analysis only) Show forest plot

3

805

Odds Ratio (M‐H, Fixed, 95% CI)

0.56 [0.39, 0.80]

1.1 6 months versus 3 months hormone therapy

2

305

Odds Ratio (M‐H, Fixed, 95% CI)

0.69 [0.41, 1.17]

1.2 8 months versus 3 months hormone therapy

1

500

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.29, 0.77]

2 pT Staging: Organ confined (Case analysis only) Show forest plot

3

805

Odds Ratio (M‐H, Fixed, 95% CI)

1.41 [1.05, 1.89]

2.1 6 months versus 3 months hormone therapy

2

305

Odds Ratio (M‐H, Fixed, 95% CI)

1.37 [0.86, 2.18]

2.2 8 months versus 3 months hormone therapy

1

500

Odds Ratio (M‐H, Fixed, 95% CI)

1.44 [0.99, 2.09]

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Comparison 2. Short‐term versus Long‐term Neo‐adjuvant hormone therapy and prostatectomy
Comparison 3. Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Disease‐specific survival Show forest plot

2

991

Odds Ratio (M‐H, Fixed, 95% CI)

0.99 [0.75, 1.32]

2 Biochemical disease‐free survival Show forest plot

3

1097

Odds Ratio (M‐H, Fixed, 95% CI)

1.93 [1.45, 2.56]

3 Clinical disease‐free survival Show forest plot

2

991

Odds Ratio (M‐H, Fixed, 95% CI)

1.86 [1.43, 2.40]

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Comparison 3. Neo‐adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone
Comparison 4. Short‐term versus long‐term neo‐adjuvant hormone therapy Radiotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 3 year biochemical disease‐free survival Show forest plot

2

893

Odds Ratio (M‐H, Fixed, 95% CI)

1.06 [0.81, 1.39]

1.1 8 verses 3 months of neoadjuvant therapy and radiotherapy

1

361

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.68, 1.56]

1.2 6 versus 3 months of neo‐adjuvant therapy and radiotherapy

1

532

Odds Ratio (M‐H, Fixed, 95% CI)

1.08 [0.76, 1.54]

2 5‐year biochemical disease free survival Show forest plot

2

893

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.67, 1.24]

2.1 8 months verses 3 months of neo‐adjuvant hormonal therapy and Radiotherapy

1

361

Odds Ratio (M‐H, Fixed, 95% CI)

1.00 [0.54, 1.85]

2.2 6 months versus 3 months of neo‐adjuvant therapy and Radiotherapy

1

532

Odds Ratio (M‐H, Fixed, 95% CI)

0.88 [0.62, 1.26]

Figures and Tables -
Comparison 4. Short‐term versus long‐term neo‐adjuvant hormone therapy Radiotherapy
Comparison 5. Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall Survival: 5 Years Show forest plot

2

407

Odds Ratio (M‐H, Fixed, 95% CI)

1.50 [0.79, 2.84]

2 Overall Survival: 10 Years Show forest plot

2

407

Odds Ratio (M‐H, Fixed, 95% CI)

0.53 [0.33, 0.84]

3 Disease‐Free Survival: 5 Years Show forest plot

2

407

Odds Ratio (M‐H, Fixed, 95% CI)

3.73 [2.30, 6.03]

4 Disease‐Free Survival: 10 Years Show forest plot

2

407

Odds Ratio (M‐H, Fixed, 95% CI)

2.06 [1.34, 3.15]

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Comparison 5. Adjuvant hormone therapy and Prostatectomy Versus Prostatectomy Alone
Comparison 6. Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall Survival: 5 Years Show forest plot

4

2844

Odds Ratio (M‐H, Fixed, 95% CI)

1.29 [1.07, 1.56]

2 Overall Survival: 10 Years Show forest plot

2

1059

Odds Ratio (M‐H, Fixed, 95% CI)

1.44 [1.13, 1.84]

3 Disease‐Specific Survival: 5 Years Show forest plot

2

1392

Odds Ratio (M‐H, Fixed, 95% CI)

2.10 [1.53, 2.88]

4 Disease‐Free Survival: 10 Years Show forest plot

2

1059

Odds Ratio (M‐H, Fixed, 95% CI)

1.96 [1.49, 2.56]

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Comparison 6. Adjuvant hormone therapy and Radiotherapy Versus Radiotherapy alone