A. Fodor

Higher-than-expected Severe (Grade 3–4) Late Urinary Toxicity After Postprostatectomy Hypofractionated Radiotherapy: A Single-institution Analysis of 1176 Patients

BACKGROUND Dose escalation and hypofractionation may have a role in postprostatectomy radiotherapy (RT), but at the risk of increasing urinary toxicity. OBJECTIVE To address predictors of severe (Grade ≥3) late urinary toxicities (LGUTOX3) after postoperative irradiation. DESIGN, SETTING, AND PARTICIPANTS A single-institution cohort of 1176 patients treated between 1993 and 2010 with adjuvant or salvage RT was analyzed. A total of 929 patients underwent conventionally fractionated (CF) RT (1.8 Gy per fraction; median dose to the prostatic bed: 70.2 Gy) with nonconformal RT (n=169), three-dimensional conformal RT (n=657), or intensity-modulated RT (n=103) technique, while 247 patients received hypofractionated helical TomoTherapy (median: 2.50 Gy per fraction) at the following doses: 117 patients at 65.8 Gy (2.35 Gy in 28 fractions), 80 patients at a median of 71.4 Gy (2.5-2.6 Gy in 28 fractions), and 50 patients at 58 Gy in 20 fractions. Total doses were converted into 2 Gy-equivalent doses (EQD2) following the linear quadratic model taking α/β=5. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable Cox regression models tested the relationship between clinicodosimetric variables and the risk of LGUTOX3 retrospectively, graded according to Common Terminology Criteria for Adverse Events v.4.0. RESULTS AND LIMITATIONS After a median follow-up of 98 mo, the 5-yr risk of LGUTOX3 was 6.9% and 18.1% in the CF and hypofractionated cohorts, respectively. At univariable analysis, the risk of LGUTOX3 was predicted by dose per fraction (hazard ratio [HR]: 2.96), acute Grade ≥2 toxicity (HR: 2.37), EQD2, pT4, and year of irradiation. At multivariable analyses, acute Grade ≥2 toxicity and dose per fraction independently predicted LGUTOX3 in the population, while an interaction analysis indicated a predictive role of hypertension in the hypofractionated cohort only. These findings are limited by their retrospective nature. CONCLUSIONS In the postprostatectomy setting, the logistic convenience of hypofractionation should be carefully balanced against the risk of severe late urinary sequelae. PATIENT SUMMARY This study investigated the causes of urinary adverse effects after postprostatectomy radiotherapy. Hypofractionation resulted in an increased risk of severe urinary toxicities.

Radiation Treatment of Lymph Node Recurrence from Prostate Cancer: Is 11C-Choline PET/CT Predictive of Survival Outcomes?

PET/CT is a valuable tool to detect lymph node (LN) metastases in patients with biochemical failure after primary treatment for prostate cancer (PCa). The aim was to assess the predictive role of imaging parameters derived by 11C-choline PET/CT on survival outcomes—overall survival, locoregional relapse-free survival, clinical relapse-free survival (cRFS), and biochemical relapse-free survival (bRFS)—in patients treated with helical tomotherapy (HTT) for LN recurrence. Methods: This retrospective study included 68 patients affected by PCa (mean age, 68 y; age range, 51–81 y) with biochemical recurrence after primary treatment (median prostate-specific antigen values obtained at the time of PET/CT scan, 2.42 ng/mL; range, 0.61–27.56 ng/mL) who underwent 11C-choline PET/CT from January 2005 to January 2013 and were treated with HTT in correspondence of the pathologic choline LN uptake. PET-derived parameters, including maximum/mean standardized uptake value (SUVmax and SUVmean, respectively) and metabolic tumor volume (MTV) with a threshold of 40%, 50%, and 60% were calculated. The best cutoff values of PET-derived parameters discriminating between patients with and without relapse, after treatment guided by PET, were assessed by receiver-operating-characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analysis including the most predictive PET-derived parameters and survival outcomes were performed. Results: The median follow-up was 20 mo (mean, 26 mo; range, 3–97 mo). 11C-choline PET/CT showed pathologic LN uptake in 4 patients at the pelvic level, in 5 at the abdominal level, in 13 at both the pelvic and the abdominal level, and in 46 at the abdominal or pelvic or other sites. The 2-y overall survival, locoregional relapse-free survival, cRFS, and bRFS were 87%, 91%, 51%, and 40%, respectively. On the basis of ROC curves, the most discriminative cutoff value for MTV values was an MTV threshold of 60% (MTV60) of greater than 0.64 cm3. No significant cutoff values were found for SUVmax or SUVmean at univariate analysis, whereas MTV60 was confirmed as an independent predictor in multivariate analysis and significantly correlated with bRFS and cRFS. MTV60 and extrapelvic disease well predict the risk of cRFS. Conclusion: 11C-choline PET/CT performed as a guide for HTT on LN recurrence is predictive of survival. In particular, MTV60 and extrapelvic disease were the best predictors of tumor response for bRFS and cRFS in PCa patients with LN recurrence after primary treatment. This information may be useful in emerging treatment strategies.