The effect of adding radiation therapy to ADT for the treatment of positive lymph nodes was assessed in an NCDB study in 20151. Compared with ADT alone, patients receiving ADT + radiation therapy was associated with a 50% decreased the risk of five-year all-cause mortality (HR 0.50, 95%CI 0.37-0.67) with a crude OS rate of 71.5% vs 53.2%. The addition of radiation therapy to ADT is also supported by data from the control arm of the STAMPEDE trial where failure-free survival outcomes favored planned the use of radiation therapy for patients with N+M0 disease (HR 0.48, 95%CI 0.29-0.79) compared to those receiving hormonal therapy only2.
Evidence for adding radiation therapy to ADT in the adjuvant setting for pN1 disease primarily draws from the landmark paper by Abdollah et al.3 in 2014. Patients with pT3b/pT4 or positive surgical margins in the setting of Gleason 7-10 disease OR patients with 3-4 positive lymph nodes derived a greater benefit from ADT + adjuvant radiation therapy compared to those receiving ADT alone. These findings were validated in a NCDB study, finding that only those with one to two positive nodes, pathological Gleason score 7-10, and pT3b/4 disease or positive surgical margins (HR 0.75, p=0.01), and those with three to four positive nodes, regardless of local tumor characteristics (HR 0.57, p=0.01)4. However, there are limitations to this retrospective population-level analysis as Dr. Wiegel notes. For instance, what are>4+ nodes? Is a patient with 5 nodes positive going to derive the same benefit as someone with 12 nodes positive? Second, there is a potential issue with lymph node density: ie. patients with 5/5 positive nodes are unlikely to derive a comparable benefit as someone with 5/30 positive nodes.
Metastasis-directed therapy has recently become a hot topic for improving outcomes in advanced prostate cancer patients. Last year’s publication of the phase II trial assessing metastasis-directed therapy in oligometastatic disease randomly assigned 62 patients (1:1) to either surveillance or metastasis-directed therapy of all detected lesions (surgery or stereotactic body radiotherapy)5 At a median follow-up of 3 years, the median ADT-free survival was 13 months for the surveillance group and 21 months for the metastasis-directed therapy group (HR 0.60, 80%CI 0.40-0.90; p = 0.11). As such, the suggestion is that this therapy should be further explored in phase III trials.
As Dr. Wiegel points out, there is already clear level 1 evidence for the efficacy of radiation therapy + ADT for patients with positive nodes. In the final analysis of the SPCG-7 study randomizing men with high and intermediate risk prostate cancer to either hormonal therapy or hormonal + radiation therapy, the 15-yr prostate cancer-specific mortality rates were 34% and 17% in the hormonal therapy and hormonal + radiation therapy arms, respectively (p<0.001)6.
Dr. Wiegel concluded by referring to the EAU guidelines that state “in patients with cN+ or pN+ prostate cancer, offer pelvic external irradiation in combination with immediate long-term ADT” (LE 2b; Gr B).
Presented by: Thomas Wiegel, MD, Professor, Clinic of Radiation Oncology University Hospital Ulm, Ulm, Germany
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
References:
- Lin CC, Gray PJ, Jemal A, et al. Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer. J Natl Cancer Inst 2015 May 9;107(7).
- James ND, Spears MR, Clarke NW, et al. Failure-free survival and radiotherapy in patients with newly diagnosed nonmetastatic prostate cancer: Data from patients in the control arm of the STAMPEDE Trial. JAMA Oncol 2016 Mar;2(3):348-357.
- Abdollah F, Karnes RJ, Suardi N, et al. Impact of adjuvant radiotherapy on survival of patients with node-positive prostate cancer. J Clin Oncol 2014 Dec 10;32(35):3939-3947.
- Abdollah F, Dalela D, Sood A, et al. Impact of Adjuvant Radiotherapy in Node-Positive Prostate Cancer Patients: The Importance of Patient Selection. Eur Urol 2018 Sep;74(3):253-256.
- Ost P, Reynders D, Decaestecker K, et al. Surveillance of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol 2018 Feb 10;36(5):446-453.
- Fossa SD, Wiklund F, Klepp O, et al. Ten- and 15-year Prostate Cancer-Specific mortality in patients with nonmetastatic locally advanced or aggressive intermediate prostate cancer, randomized to lifelong endocrine treatment alone or combined with radiotherapy: Final results of the Scandinavian Prostate Cancer Group-7. Eur Urol 2016;70(4):684-691.
Treatment of Positive Pelvic Lymph Nodes: Surgery
Treatment of Positive Pelvic Lymph Nodes: Genomics
Treatment of Positive Pelvic Lymph Nodes: Systemic Treatments