Radiation Oncology/Prostate/Node Positive

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Front Page: Radiation Oncology | RTOG Trials | Randomized Trials

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Prostate: Main Page | Prostate Overview | Screening and Prevention | Workup | Natural History | External Beam RT | IMRT | Androgen Suppression Therapy | Brachytherapy | Protons | Prostatectomy | Adjuvant RT after Prostatectomy | Salvage RT | Chemotherapy | Localized prostate cancer | Node Positive | Advanced disease | Recurrence after RT | Cryotherapy | RTOG Prostate Trials | Randomized Evidence

Long-term outcomes[edit]

  • RTOG 75-06 - PMID 9531359 — Ten-year outcomes for pathologic node-positive patients treated in RTOG 75-06. (Hanks GE, IJRBOP 1998).
    • Conclusion: A small fraction of node-positive patients are cured at 10-year follow-up by radiation therapy (2 of 90 with PSA +3 of 90 by clinical endpoints). Innovative treatment programs should be directed at node-positive patients in an effort to improve the fraction cured.

Local Therapy vs No Local Therapy[edit]

  • SEER/U. Colorado PMID 24661660 - "The Impact of Definitive Local Therapy for Lymph Node–Positive Prostate Cancer: A Population-Based Study " (Rusthoven CG, Int J Radiat Oncol Biol Phys 2014; 88 (5); 1064-1073. )
    • 1995-2005, 796 clinically node positive (cN+), 2991 pathologically node positive (pN+), analyzed as separate cohorts.
      • For cN+ patients, 43% had EBRT vs 57% had No Local Therapy (NLT). 10-yr OS 45% vs 29% (P<.001) (median OS 9.6 vs 5.9 yr)
      • For pN+ patients, 78% had local therapy (radical prostatectomy (RP) 57%, EBRT 10%, or both 11%) vs 22% had NLT. 10-yr OS 65% vs 42% (P<.001) (median OS 13.6 vs 8.3 years)
      • Local therapy beneficial across subgroups, including age >=70 years and multiple +lymph nodes
    • Secondary comparisons of RP vs EBRT and RP +/- Adjuvant EBRT: no significant differences between modalities. +Trend toward improved OS with RP + Adjuvant EBRT over RP alone (p=.08).
    • Conclusion: "RP and EBRT were associated with substantial improvements in OS and PCSS. The best available evidence suggests that patients with N1M0 PCa can achieve improved long-term survival outcomes with definitive local therapy and these strategies should be considered in appropriate candidates."
    • "Mixed Population Model" - authors propose a model to account for potential "under-ascertainment" of radiation data (ie, coding "no radiation" in SEER registries when radiation was actually delivered to the patient [Jagsi Cancer 2012;118:333-341, Walker IJROBP 2013;86:686-693]):
      • OSmixed_population=R(OSradiation)+(1−R)(OSno_radiation)
        • "...where OSmixed_population is the observed survival in the population coded as undergoing no radiation therapy (eg, NLT or RP alone), OSradiation is the observed survival for patients known with certainty to have received radiation therapy, R is the proportion of patients in the mixed population who actually received radiation therapy (ie, the rate of underascertainment), and OSno_radiation is the derived survival estimate for a given value of R. Notably, this model assumes that patients in the mixed population who actually received radiation have survival outcomes similar to those in the population known to have received radiation (OSradiation)""
        • Using this model, with hypothetical under-ascertainment rates of 10% and 20%, the authors find that SEER could potentially underestimate the 10 year OS benefit of radiation (vs NLT) by 2-4% and the 10 year OS benefit of adjuvant radiation (vs RP alone) by 0-1% in this population.

Prostatectomy vs Radiotherapy[edit]

  • Ulm, Germany / U. Michigan PMID 15356680 -- Comparison of external radiation therapy vs radical prostatectomy in lymph node positive prostate cancer patients. (2004 Kuefer, Prostate Cancer Prostatic Dis. 2004;7(4):343-9.)
    • Retrospective. 102 pts RPX, 44 pts ERT. Adjuvant androgen ablation was given in 76 of 102 RPX, 21 of 44 ERT.
    • Conclusion: "In case of positive lymph nodes, RPX and ERT might be considered and need to be explained to the patient. For future treatment decisions, the presented findings and a potential survival benefit need to be evaluated in a larger prospective setting."

Radiotherapy alone[edit]

Dose for positive nodes:

  • From Fletcher, Texbook of Radiotherapy, 3rd ed. (1980) - For lymphangiogram positive pelvic nodes, extend field to L4-L5 interspace, 45 Gy to pelvis + boost positive nodes to a total of 55-60 Gy.

After prostatectomy[edit]

Hormonal therapy after prostatectomy[edit]

Randomized data:

  • Messing / ECOG EST-3886 (1988 - 93)
    • 7 years, 1999 PMID 10588962 Full text — "Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer." (Messing EM, N Engl J Med. 1999 Dec 9;341(24):1781-8.)
      • 98 pts. Pts were found to have node-positive disease after radical prostatectomy + pelvic lymphadenectomy. Randomized to adjuvant goserelin (or bilateral orchiectomy) vs observation until disease progression (based on local or distant disease progression, not PSA).
      • Median 7.1 yrs f/u. 77% (antiandrogen) vs 18% (obs) were alive with no evidence of recurrent disease and undetectable PSA. Death from any cause in 7 of 47 men (antiandrogen) vs 18 of 51 (obs), S.S.
      • Conclusion: survival benefit for immediate hormonal therapy. RT not used.
    • 12 years, 2006 PMID 16750497 -- "Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy." (Messing EM, Lancet Oncol. 2006 Jun;7(6):472-9.)
      • Median f/u 11.9 yr. Improved OS (HR=1.84), PCSS (HR=4.09) , and PFS (HR=3.42).

Retrospective:

  • SEER/Medicare; 2009 (1991-1999) PMID 19047295 -- "Role of androgen deprivation therapy for node-positive prostate cancer." (Wong YN, J Clin Oncol. 2009 Jan 1;27(1):100-5.)
    • 731 pts treated with RP with positive regional LNs. 209 men received ADT within 120 days of RP. Compared men receiving adjuvant ADT vs those without adjuvant ADT.
    • OS: no sig difference between adjuvant ADT and non-ADT groups (HR 0.97).
    • CONCLUSION: "Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival."

Adjuvant hormonal therapy plus RT[edit]

  • Italy, 2011 (1986-2002) - Retrospective, multi-center
    • 364 pts (of a series of 703 pts), pLN+ treated with RP. Matched analysis comparing 117 pts treated with HT + RT vs 247 pts treated with HT alone.
    • 2011 PMID 21354694 -- "Combination of adjuvant hormonal and radiation therapy significantly prolongs survival of patients with pT2-4 pN+ prostate cancer: results of a matched analysis." (Briganti A, Eur Urol. 2011 May;59(5):832-40.)
      • Median f/u 95 mo. (7.9 yr). 5/8-year CSS 90%/82%, OS 85%/70%. Pts treated with RT+HT had higher CSS and OS rates (5/8-year CSS: 95%/91% vs 88%/78%, OS: 90%/84% vs 82%/65%).
      • Conclusion: "Adjuvant RT plus HT significantly improved CSS and OS of pT2-4 pN1 patients, regardless of the extent of nodal invasion. These results reinforce the need for a multimodal approach in the treatment of node-positive prostate cancer."
  • Italy, 2009 (1988-2002) - Retrospective
    • Retrospective review of 250 consecutive pLN+ patients treated with RP, followed by HT alone (48%) or HT and RT (52%). Seventy-four percent of patients received pelvic and prostate bed RT. Median dose 66.6 Gy.
    • 2009 PMID 19211184 -- "Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy." (Da Pozzo LF, Eur Urol. 2009 May;55(5):1003-11.)
      • 5/8-year bRFS 72/61%, CSS 89/83%. In multivariate analysis, adjuvant RT and # of positive LN predicted bRFS and CSS. Patients treated with aHT alone had 2.6× risk of prostate cancer mortality vs. HT and RT after accounting for other predictors.

Hormonal therapy and radiotherapy[edit]

  • MD Anderson, 2001 (1984-1998) PMID 11489709 — "Addition of radiation therapy to androgen ablation improves outcome for subclinically node-positive prostate cancer." Zagars GK, Pollack A, von Eschenbach AC. Urology. 2001 Aug;58(2):233-9.
    • Retrospective. 255 pts N+ found on lymphadenectomy treated with early androgen ablation alone (n=188) or with 70 Gy EBRT (n=72). Median F/U 9.4 years for ablation alone, 6.2 years for ablation + RT
    • 10 year outcome: Adding EBRT improved OS from 46 to 67%. Freedom from relapse improved from 25% to 80%
    • Conclusion: Early androgen ablation alone not helpful. Addition of RT offers substantial and significant improvement
  • RTOG 85-31: Subset Analysis, PMID 15681524 — "Androgen suppression plus radiation versus radiation alone for patients with stage D1/pathologic node-positive adenocarcinoma of the prostate: updated results based on national prospective randomized trial Radiation Therapy Oncology Group 85-31." Lawton CA et al. J Clin Oncol. 2005 Feb 1;23(4):800-7.
    • Updated analysis of pN+ pts (median f/u on all pts (6.5 yrs) and all living pts (9.5 yrs))
    • 98 pts XRT + immediate adjuvant goserelin, 75 pts XRT alone w/ delayed goserelin @ time of failure.
    • Conclusion: Multivariant analysis shows XRT + immediate adj goserelin have SS benefit in all four end points analyzed-- biochem control, met failure, DSF, absolute survival. Need prospective randomized trial to confirm, but until then, pN+ pts should be considered for XRT + immediate hormonal manipulation rather than XRT alone with hormone manipulation at the time of relapse.
  • (closed due to poor accrual ) RTOG 96-08 (1997-98)
    • Randomized node-positive pts to indefinite total androgen ablation vs total androgen ablation plus RT to the pelvis + prostate. 50.4 Gy to the pelvis (to L4/5 interspace) with boost to 68.4 - 70.2 Gy.


Hormonal Therapy Alone[edit]

  • EORTC 30846 - Randomized to immediate ADT vs delayed ADT; no treatment of the primary tumor
    • 234 pts with prostate cancer and nodal metastases. No treatment to the primary tumor was given. Pts randomized to early ADT vs delayed ADT. Non-inferiority trial
    • 2009 PMID 18823693 -- "Early versus delayed endocrine treatment of T2-T3 pN1-3 M0 prostate cancer without local treatment of the primary tumour: final results of European Organisation for the Research and Treatment of Cancer protocol 30846 after 13 years of follow-up (a randomised controlled trial)." (Schröder FH, Eur Urol. 2009 Jan;55(1):14-22.)
      • Median f/u 13 yr. Median duration of protocol ADT 2.7 yr (delayed) vs 3.2 yr (immediate).
      • 59.4% of pts died from PCa; 82.5% died overall. Median OS 6.1 yr (delayed) vs 7.6 yr (immediate) (HR 1.22), not signficant (non-inferiority not proven).
      • Conclusion: "After 13 years of follow-up, survival or PCa-specific survival between immediate and delayed ET appear similar, but the trial is underpowered to reach its goal of showing non-inferiority."