Impact of Adjuvant Radiotherapy on Survival of Patients With Node-Positive Prostate Cancer Firas Abdollah, R. Jeffrey Karnes, Nazareno Suardi, Cesare Cozzarini, Giorgio Gandaglia, Nicola Fossati, Damiano Vizziello, Maxine Sun, Pierre I. Karakiewicz, Mani Menon, Francesco Montorsi, and Alberto Briganti See accompanying editorial on page 3917 and article on page 3926 Firas Abdollah and Mani Menon, Henry Ford Hospital, Detroit, MI; R. Jeffrey Karnes, Mayo Clinic, Rochester, MN; Nazareno Suardi, Cesare Cozzarini, Gior- gio Gandaglia, Nicola Fossati, Damiano Vizziello, Francesco Montorsi, and Alberto Briganti, Vita-Salute San Raffa- ele University, Milan, Italy; and Maxine Sun and Pierre I. Karakiewicz, Univer- sity of Montreal Health Centre, Montreal, Quebec, Canada. Published online ahead of print at www.jco.org on September 22, 2014. Terms in blue are defined in the glos- sary, found at the end of this article and online at www.jco.org. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Alberto Briganti, MD, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; e-mail: briganti.alberto@hsr.it. © 2014 by American Society of Clinical Oncology 0732-183X/14/3235w-3939w/$20.00 DOI: 10.1200/JCO.2013.54.7893 A B S T R A C T Purpose The role of adjuvant radiotherapy (aRT) in treating patients with pN1 prostate cancer is controversial. We tested the hypothesis that the impact of aRT on cancer-specific mortality (CSM) in these individuals is related to tumor characteristics. Methods We evaluated 1,107 patients with pN1 prostate cancer treated with radical prostatectomy and anatomically extended pelvic lymph node dissection between 1988 and 2010 at two tertiary care centers. All patients received adjuvant hormonal therapy with or without aRT. Regression tree analysis stratified patients into risk groups on the basis of their tumor characteristics and the corresponding CSM rate. Cox regression analysis tested the relationship between aRT and CSM rate, as well as overall mortality (OM) rate in each risk group separately. Results Overall, 35% of patients received aRT. At multivariable analysis, aRT was associated with more favorable CSM rate (hazard ratio [HR], 0.37; P  .001). However, when patients were stratified into risk groups, only two groups of men benefited from aRT: (1) patients with positive lymph node (PLN) count  2, Gleason score 7 to 10, pT3b/pT4 stage, or positive surgical margins (HR, 0.30; P = .002); and (2) patients with PLN count of 3 to 4 (HR, 0.21; P = .02), regardless of other tumor characteristics. These results were confirmed when OM was examined as an end point. Conclusion The beneficial impact of aRT on survival in patients with pN1 prostate cancer is highly influenced by tumor characteristics. Men with low-volume nodal disease ( two PLNs) in the presence of intermediate- to high-grade, non–specimen-confined disease and those with intermediate-volume nodal disease (three to four PLNs) represent the ideal candidates for aRT after surgery. J Clin Oncol 32:3939-3947. © 2014 by American Society of Clinical Oncology INTRODUCTION The presence of lymph node invasion (LNI) in pa- tients with prostate cancer (PCa) treated with radical prostatectomy (RP) represents an adverse patho- logic finding associated with a detrimental impact on cancer control outcomes. 1-7 Despite the signifi- cant downward PCa stage migration during the last two decades, up to 14% of contemporary patients still harbor LNI at surgery. 8,9 The optimal postoper- ative management of these patients is still under debate. 10 Indeed, although adjuvant hormonal ther- apy (aHT) is indicated by all current guidelines based on a Level I evidence trial, 11,12 recent evidence suggests good long-term outcomes for selected pa- tients with LNI without aHT. 13 Moreover, retro- spective data have supported a potential benefit of adjuvant radiotherapy (aRT) on patient survival when combined with aHT. 4,14,15 The aim of aRT in these patients would be to maximize local control, given the non-negligible risk of local failure in these patients after surgery. 16 Patients with LNI represent a highly heterogeneous population sharing different survival rates according to their pathologic charac- teristics. 1,2,5 Therefore, it is possible that the poten- tial beneficial impact of any adjuvant therapy could significantly vary according to the tumor character- istics of each patient. We hypothesized that the effect of aRT on survival of men with LNI treated with RP strongly depends on the primary PCa tumor fea- tures. Such a finding could lead to the identification of subgroup(s) of men with nodal metastases who would represent the ideal candidate for aRT, thus sparing unnecessary treatments and related adverse effects in the remaining patients. JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 32  NUMBER 35  DECEMBER 10 2014 © 2014 by American Society of Clinical Oncology 3939 Downloaded from jco.ascopubs.org on June 5, 2016. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.