Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer Andrei Fodor*, Genoveffa Berardi*, Claudio Fiorino † , Maria Picchio ‡ , Elena Busnardo ‡ , Margarita Kirienko § , Elena Incerti ‡ , Italo Dell’Oca*, Cesare Cozzarini*, Paola Mangili † , Marcella Pasetti*, Riccardo Calandrino † , Luigi Gianolli ‡ and Nadia G Di Muzio* *Department of Radiation Oncology, † Department of Medical Physics, ‡ Department of Nuclear Medicine, San Raffaele Scientific Institute, and § Nuclear Medicine, University Milano-Bicocca, Milan, Italy Objective To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/ computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy â Hi-Art II â Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. Patients and Methods From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61– 187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C- choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50–65.5 Gy, 25–30 fr). Results With a median (range) follow-up of 36 (9–116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (Æ2.9%) and 26.3% (Æ5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7–7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9–6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07–6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04–1.22; P = 0.003) were the main predictors of clinical relapse after HTT. Conclusions 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients. Keywords prostate cancer, lymph node recurrence, salvage radiation therapy, 11C- Choline PET/CT Introduction The standard treatment of lymph node (LN) recurrence of prostate cancer, considered as metastatic disease, is androgen deprivation therapy (ADT) until resistance, and chemotherapy or a combination of ADT and chemotherapy as second-line therapy [1]. The progression delay for all systemic treatments is several months [2–5]. Positron emission tomography (PET)/CT with carbon 11 (11C)- choline and fluorine-18-labelled (18F)-choline PET/CT is considered appropriate for the diagnosis of prostate cancer lymph node relapse [6,7], with results validated by open lymphadenectomy [7,8]. The use of PET-guided LN dissection or radiotherapy (RT) with therapeutic intent have been reported to reduce disease burden and delay clinical progression [9–12]. Retrospective studies suggest better overall survival (OS) and progression- free survival in patients with LN metastases treated with RT + ADT vs ADT only [13]. Salvage 11C-choline-PET/ © 2016 The Authors BJU International © 2016 BJU International | doi:10.1111/bju.13510 BJU Int 2016 Published by John Wiley & Sons Ltd. www.bjui.org wileyonlinelibrary.com