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. 2019 Feb 6;15(3):108–120. doi: 10.1111/ajco.13108

Table 1.

Summary of results from key clinical trials that investigated ADT as neoadjuvant, adjuvant therapy, or treatment at biochemical recurrence in patients with prostate cancer who received radical prostatectomy

Study (years) Level of evidencea Study type N Patient characteristics Treatment and duration Outcomes
(1966–2006)7 1 Meta‐analysis 11 149 Localized or locally advanced PC with or without lymph node involvement (T1‐4, N1, M0) Neoadjuvant ADT + RP versus RP alone

  • OS: OR, 1.11 (0.67–1.85); P = 0.69

  • Disease recurrence: OR, 0.74 (0.55–1.0); P = 0.05

  • Positive surgical margin rate: OR, 0.34 (0.27–0.42); P < 0.00001
(1966–2006)7 1 Meta‐analysis 11 149 Localized or locally advanced PC with or without lymph node involvement (T1‐4, N1, M0) Adjuvant ADT following RP versus RP alone

  • 5‐y OS: OR, 1.50 (0.79–2.85); P = 0.2

  • 5‐y DFS: OR, 3.73 (2.3–6.03); P < 0.00001

  • 10‐y DFS: OR, 2.06 (1.34–3.15); P = 0.0009
Timing Of Antigen Deprivation (TOAD) therapy in patients with prostate cancer27 (2004–2012) 2 Prospective, randomized, phase 3 293 PSA relapse after curative treatment (RP or RT), or ineligible for curative treatment Immediate salvage ADT or delayed salvage ADT (recommended interval ≥ 2 y, unless clinically indicated)

  • 5‐y OS: 91.2% (84.2–95.2) versus 86.4% (78.5–91.5); P = 0.047

  • Among men with PSA relapse, 5‐y OS: 84.3% (73.9–90.8) versus 78.2% (67.2–85.8); P = 0.10
French Genito‐Urinary Group and the French Association of Urology (GETUG‐AFU) 1628 (2006–2010) 2 Prospective, randomized, phase 3 743 pT2‐4a PC with rising PSA of 0.2–2.0 ng/mL following RP without evidence of clinical disease Salvage RT (66 Gy in 33 fractions 5 d/wk for 7 wk) + 6 mo ADT (goserelin) versus salvage RT alone

  • 5‐y PFS: 80% (75–84) versus 62% (57–67); HR, 0.50 (0.38–0.66); P < 0.0001
Radiation Therapy Oncology Group (RTOG) 960129 (1998–2003) 2 Prospective, randomized, phase 3 760 pT3pN0 or pT2pN0 and positive margins; rising PSA (0.2–4.0 ng/mL) following RP ADT (bicalutamide 150 mg daily for 2 y) during and after salvage RT (64.8 Gy in 36 fractions of 1.8 Gy) versus salvage RT alone

  • 12‐y OS: 76.3% versus 71.3%; HR, 0.77 (0.59–0.99); P = 0.04

  • 12‐y PC: 5.8% versus 13.4%; P < 0.001

  • 10‐y PC deaths: 4.5% versus 10.1%; P < 0.001
Eastern Cooperative Oncology Group (ECOG) 388616 (1988–1993) 2 Prospective, randomized 98 Clinically localized PC (T1b or T2) and had previously undergone RP + PLND Immediate adjuvant ADT (goserelin monthly or bilateral orchiectomy) versus RP + salvage ADT

  • Median OS: 13.9 y versus 11.3 y; HR, 1.84 (1.01–3.35); P = 0.04

  • Median DSS: NR versus 12.3 y; HR, 4.09 (1.76–9.49); P = 0.0004

  • Median PFS: 13.9 y versus 2.4 y; HR, 3.42 (1.96–5.98); P < 0.0001
Southwest Oncology Group (SWOG) S992117, 20 (2000–2007) 2 Prospective, randomized 983 High‐risk features at RP (GS ≥ 8; preop PSA ≥ 15 ng/mL; stage T3b, T4, or N1; or GS = 7 + preop PSA ≥ 10 ng/mL or a positive margin) Adjuvant ADT (goserelin + bicalutamide) alone or in combination with mitoxantrone chemotherapy for 2 y

  • 10‐y DFS: 72% versus 72%; HR, 1.01 (0.80–1.27); P = 0.94

  • 10‐y OS: 87% versus 86%; HR, 1.06 (0.79–1.43); P = 0.70

  • Deaths due to other cancer: 18% versus 36%; P = 0.011

  • Deaths due to leukemia: 0.2% versus 1.0%
SWOG 91092 (1993–1996) 2 Prospective, phase 2 62 Locally advanced (T3–4, N0M0) PC Neoadjuvant ADT (goserelin [1 mo] + flutamide [4 mo]) followed by RP

  • Median PFS: 7.5 y

  • 10‐y PFS: 40% (27–53%)

  • Median OS: NR

  • 10‐y OS: 68% (56–80%)
(2004–2012)8 3 Retrospective 156 High‐risk (T1c–3) PC Neoadjuvant therapy (LHRH agonist + estramustine for 6 mo) followed by RP versus neoadjuvant ADT for ≥6 mo followed by RT (3D conformal, 70–76 Gy in 2 Gy fractions)

  • 3‐y OS: 98.3% versus 92.1% (P = 0.156)

  • 3‐y BFS: 86.4% versus 89.4% (P = 0.878)
(2000–2014)9 3 Retrospective 518 High‐risk PC Neoadjuvant therapy (LHRH agonist and for 6 mo + l‐PLND and RP versus e‐PLND and RP only)

  • 5‐y BFS: 84.9% (80.4–59.4%) versus 54.7% (53.9–62.5%)
(2002–2013)10 3 Retrospective 111 High‐risk PC Neoadjuvant hormonal therapy followed by RP

  • Six pts with pT0: no recurrence after median follow‐up of 59 mo

  • 105 pts with non‐pT0: 57.1% developed BCR within a median of 14 mo
(2000–2014)11 3 Retrospective 116 Initially inoperable PC Neoadjuvant ADT for ≥3 mo or until PSA nadir reached followed by RP Median OS: 10 y, comparable with that of patients with initially operable high‐risk PC
(2000–2006)18 3 Retrospective 128 Locally advanced (pT3N0M0) PC Immediate adjuvant ADT for ≥5 y

  • 10‐y hormone‐refractory BFS: 88.3%

  • 10‐y DSS: 96.3%

  • 10‐y OS: 85.7%
(1990–1999)19 3 Matched cohort 8290 Pathological lymph node‐negative PC RP + adjuvant ADT versus RP alone

  • 10‐y systemic PFS: 95% versus 90%; P < 0.001

  • 10‐y DSS: 98% versus 95%; P = 0.009

  • 10‐y OS: 84% versus 83%; P = 0.427
(1989–2005)21 3 Retrospective 372 High risk (PSA > 20 ng/mL, ≥T2c, or GS ≥ 8) PC RP + adjuvant ADT (LHRH agonist, LHRH agonist/orchiectomy + oral antiandrogen, or orchiectomy alone) if seminal vesicle invasion or lymph node metastases were present versus RP alone

  • 5‐y BFS: 76.6%

  • 10‐y BFS: 56.2%

  • BFS with versus without ADT: P = 0.0019

  • 5‐y OS: 84.3%

  • 10‐y OS: 72.1%

  • OS with versus without ADT: P = 0.0821
(2004–2012)26 3 Retrospective 132 High‐risk PC (pelvic lymph node invasion, lymphovascular invasion, high tumor grade, or high preop PSA) Adjuvant RT + adjuvant ADT (LHRH agonist or bicalutamide 150 mg/d) versus adjuvant RT alone following RP; duration of ADT left to the discretion of the physician

  • Among 56 patients treated with RT + ADT:

  • 5‐y BFS: 90.5%

  • 5‐y MFS: 95.9%

  • 5‐y DSS: 100%

  • 5‐y OS: 90.6%

  • Median duration of ADT: 24 mo (6–36)

ADT, androgen deprivation therapy; BCR, biochemical recurrence; BFS, biochemical progression‐free survival; DFS, disease‐free survival; DSS, disease‐specific survival; GS, Gleason score; HR, Hazards ratio; LHRH, luteinizing hormone‐releasing hormone; MFS, metastasis‐free survival; NR, not reported; OS, overall survival; OR, odds ratio; preop, preopeartive; PC, prostrate cancer; PFS, progression‐free survival; PLND, pelvic lymph node dissection; PSA, prostate‐specific antigen; RP, radical prostatectomy; RT, radiotherapy.

a

Level of evidence determined by study design: 1, meta‐analysis or systematic review; 2, randomized controlled trial; and 3, cohort study.