Table 3. Summary of results from selected studies evaluating the treatment of very high risk prostate cancer patients with locally advanced or clinically node positive disease.
| Study | No. of Patients | Eligibility criteria | Treatment | Median follow-up | Outcome |
|---|---|---|---|---|---|
| Radical prostatectomy for patients presenting with locally advanced disease | |||||
| Johnstone et al.44 | 1,093# | cT4, N0 or N1, M0 | RP ± RT/ADT vs. RT vs. ADT vs. RT+ ADT vs. NT | NA | 5-year OS 72.6% (RP ± RT/ADT), 61.8% (RT), 41.5% (ADT), 71.1% (RT+ADT), 39.8% (NT) Patients treated locally (RT, RP) had significantly better OS than ADT alone or NT |
| Moltzahn et al.45 | 266 | cT3b-4, N0 or N1, M0 | RP + PLND ± adjuvant ADT and/or RT | 9.3 years | 10-year CSS 87.1%- 94.4%; 10-year other-cause mortality 10%-38% |
| Adjuvant radiation therapy after radical prostatectomy for patients with adverse pathology | |||||
| EORTC 2291147,48 | 1,005 | pT2-3, N0 + ≥1 risk factor: PSM, SVI, EPE | RP + adjuvant RT vs. RP + observation$ | 10.6 years (IQR 8.4-12.5) | 10-year biochemical PFS 60.6% vs. 41.1% (HR 0.49; 95% CI 0.41–0.59; p<0·0001); 10-year clinical PFS 70.3% vs. 64.8% (HR 0.81; 95% CI 0.65–1.01; p=0.054); 10-year OS 76.9% vs. 80.7% (HR 1.18; 95% CI 0.91–1.53; p=0.202); 10-year CSS 96.1 vs. 94.6% (HR 0.78; 95% CI 0.46–1.33; p=0.341) |
| SWOG 879449,50 | 431 | pT3, N0 ± PSM | RP + adjuvant RT vs. RP + observation$ | 12.7 years (IQR 11.4-15.1) | 10-year metastasis free survival 71% vs. 61% (HR 0.71; 95% CI 0.54-0.94; p=0.016); 10-year OS 74% vs. 66% (HR 0.72; 95% CI 0.55-0.96; p=0.023) |
| ARO 96-0251,52 | 388 | pT3-4, N0 ± PSM and undetectable PSA after RP | RP + adjuvant RT vs. RP + observation$ | 9.3 years | 10-year biochemical PFS 56% vs. 35% (HR 0.51; 95% CI 0.37–0.70; p<0.0001); Metastasis free survival and OS were not significantly improved by RT% |
| External beam radiation therapy + long term androgen deprivation therapy | |||||
| EORTC 2286355,56 | 415 | cT1-2 + WHO grade 3 or cT3-T4 + any histological gradeˆ | RT vs. RT + ADT (3 years) | 9.1 years (IQR 5.1-12.6) | 10-year RFS 23% vs. 48% (p<0.001); 10-year OS 40% vs. 59% (p<0.001); 10-year PCM 30% vs. 10% (p<0.001) |
| RTOG 85-3157,58 | 977 | cT3 or N1 or RP + PSM and/or SVI | RT vs. RT + ADT (lifelong) | 11 years | 10-year OS 39% vs. 49%, p=0.002; 10-year CSS 78% vs. 84%, p=0.005; 10-year metastasis free survival 61% vs. 76%, p<0.0001 |
| Warde et al.59 | 1,205 | T3-4, N0/Nx, M0 or T2 + PSA>40 or T2 + PSA>20 + GS>8 | ADT (lifelong) vs. ADT + RT | 6 years (IQR 4.4–8.0) | 7-year OS 66% vs. 74% (HR 0.77; 95% CI 0.61–0.98; p=0.033); 7-year CSS 81% vs. 91% (HR 0.54, 0.27–0.78, p=0.0001) |
| SPCG-7/SFUO-360 | 875 | cT1b-T2, N0, M0 + WHO grade 2-3, or cT3, N0, M0 + any WHO grade, and PSA≤70 ng/ml& | ADT (lifelong) vs. ADT + RT | 7.6 years (range 0.2–11.9 years) | 10-year CSS 76% vs. 88% (RR 0.44, 95% CI 0.30–0.66, p<0.001); 10-year OS 61% vs. 70% (RR 0.68, 95% CI 0.52–0.89, p=0.004); 10-year biochemical RFS 25% vs. 74% (RR 0.16, 95% CI 0.12–0.20, p<0.0001) |
| Intergroup randomized study61 | 1,205 | cT3-4, N0/Nx, M0 or cT1-2 with either PSA > 40 ng/ml or PSA 20-40 ng/ml and GS 8-10 | ADT (lifelong) vs. ADT + RT | 8 years (range, 0-15.2 years) | 10-year OS 49% vs. 55% (HR=0.7, 95% CI 0.57-0.85, P<0.001); CSS higher in combined treatment (HR 0.46, 95% CI 0.34-0.61, p<.001); 10-year PFS 46% vs. 74% (HR 0.31, 95% CI 0.25-0.39) |
| Early chemotherapy for high risk locally advanced disease | |||||
| RTOG 990288 | 397 | High risk PCa (PSA 20-100ng/mL and GS ≥ 7 with any T stage, or clinical stage ≥T2 and GS 8-10 and PSA ≤ 100ng/mL), N0, M0 | ADT (2 years) + RT + CT (estramustin, etoposide, and paclitaxel) vs. ADT + RT | 9.2 years (range 0.4-13.3)∼ | 10-year OS 63.1% vs. 65.4% (HR 1.04; 95% CI 0.76-1.43; p=0.81); 10-year RFS 25.8% vs. 22.2% (HR 0.94; 95% CI 0.75-1.19, p=0.61) |
| STAMPEDE75 | 638/ 2,962* | High risk locally advanced PCa with ≥2 of the following: T3-4, GS 8–10, and PSA ≥40 ng/mL | SOC vs. SOC + zoledronic acid vs. SOC + docetaxel vs. SOC + zolderonic acid and docetaxel | 3.6 years (IQR 2.5-5) | 5-year OS 55% vs. 57% vs. 63% vs. 60%; Survival advantage for SOC + docetaxel (HR 0.78, 95% CI 0.66–0.93; p=0·006) and for SOC + docetaxel + zoledronic acid (HR 0.82, 95% CI 0.69–0.97; p=0·022) compared to SOC only Failure free survival was improved in patients with non-metastatic disease (HR 0.60, 95% CI 0.45–0.80; p<0.001) |
| GETUG 1290 | 413 | Treatment-naïve PCa + ≥1 risk factor: pT3–T4, GS ≥8, PSA >20 ng/mL, or pN1+ | ADT (3 years) + local treatment + CT (docetaxel and estramustine) vs. ADT + local treatment | 8.8 years (IQR 8.1–9.7) | 8-year RFS 62% vs. 50% (adjusted HR=0.71, 95% CI 0.54–0.94, p=0.017) |
| RTOG 052191 | 562 | GS 7-8, any T stage, and PSA > 20 or GS 8, stage ≥T2, any PSA or GS 9-10, any T stage, any PSA; All had PSA ≤150 | ADT (2 years) + RT + CT (docetaxel + prednisone) vs. ADT + RT | 5.5 years | 4-year OS 93% vs. 89% (HR 0.68, 95% CI 0.44-1.03, 1 sided p=0.03); 5-year RFS 73% vs. 66% (HR 0.76, 95% CI 0.57-1.00, 2 sided p=0.05) |
| External beam radiation therapy for clinically node positivedisease | |||||
| Rusthoven et al.94 | 796 | cT1-4, N1, M0 | RT vs. no local treatment | 5.2 years | 10-year OS 45% vs. 29% (HR 0.58; 95% CI 0.48-0.71; p<.001); 10-year CSS 67% vs. 53% (HR 0.61; 95% CI 0.47-0.80; p<.001) |
| Lin et al.95 | 3,540 | cN1, M0 or Mx | ADT + RT vs. ADT alone | 5.2 years | 5-year OS 71.5% vs 53.2% (HR 0.50; 95% CI 0.37-0.67; p < .001) |
No. = number; RP = radical prostatectomy; RT = radiation therapy; ADT = androgen deprivation therapy; NT = no treatment; NA = not applicable; OS = overall survival; PLND = pelvic lymph node dissection; CSS = cancer specific survival; EORTC = European Organization for Research and Treatment of Cancer; PSM = positive surgical margins; SVI = seminal vesicle invasion; EPE = extraprostatic extension; IQR = inter-quartile range; PFS = progression free survival; HR = hazard ratio; CI = confidence interval; SWOG = Southwest Oncology Group; WHO = World Health Organization; RFS = recurrence free survival; PCM = prostate cancer mortality; RTOG = Radiation Therapy Oncology Group; SPCG = Scandinavian Prostate Cancer Group; SFUO = Swedish Association for Urological Oncology; RR = relative risk; PCa = prostate cancer; CT = chemotherapy; STAMPEDE = Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy; SOC = standard of care; GETUG = Genito-Urinary Tumor Group
72 patients underwent radical prostatectomy.
Treatment was delayed until biochemical or clinical relapse.
The study was underpowered to evaluate the endpoints of metastasis free survival and overall survival.
Patients with cT3-4 disease represent approximately 90% of the study cohort.
78% of patients had a T3 disease.
The trial was terminated prematurely due to a high rate of thromboembolic events in the chemotherapy arm.
Represents the number of patients with newly diagnosed high risk N0M0 disease and the total number of patients included in the study.
All patients underwent a staging pelvic lymph node dissection.