Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis.

Background: The objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT). Materials and methods: This observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson's comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed. Results: A total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/ß=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox's regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008). Conclusions: The unexpected results of this analysis could be explained by a "response shift bias" concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens.

Simultaneous Integrated Radiotherapy Boost to the Dominant Intraprostatic Lesion: Final Results of a Phase I/II Trial.

BACKGROUND/AIM: Late toxicity and long-term outcomes of a phase I-II trial on patients with prostate cancer treated with an integrated boost to the dominant intraprostatic lesion (DIL) are reported. PATIENTS AND METHODS: Patients were treated using intensity-modulated radiotherapy, with a simultaneous integrated boost to the DIL, defined on staging magnetic resonance imaging, delivering 72 Gy in 1.8 Gy/fraction to prostate/seminal vesicles and 80 Gy in 2 Gy/fraction to the DIL. The primary endpoint was acute toxicity and secondary endpoints were late toxicity and biochemical disease-free survival. RESULTS: Forty-four patients were enrolled. The median follow-up was 120 (range=25-150) months. Five-year rates of grade 3 late gastrointestinal and genitourinary toxicity were 2.3% and 4.5%, respectively; only one grade 4 late genitourinary toxicity was recorded. Five-year biochemical relapse-free and overall survival rates were 95.3% and 95.5%, respectively. CONCLUSION: The treatment was well tolerated and achieved excellent results in terms of outcome in patients with low-intermediate Gleason's score and low risk of nodal metastasis.

Definition of fields margins for the optimized 2D radiotherapy of prostate carcinoma.

Prostate cancer (PCa) is one of the most common malignancies in men both in western and developing countries. Radiotherapy (RT) is an important therapeutic option. New technologies (including 3D, intensity modulated RT, image-guided RT and, volumetric modulated arc therapy) have been introduced in the last few decades with progressive improvement of clinical outcomes. However, in many developing countries, the only treatment option is the traditional two-dimensional (2D) technique based on standard simulation. The guidelines for 2D field definition are still based on expert's opinions. The aim of the present study was to propose new practical guidelines for 2D fields definition based on 3D simulation in PCa. A total of 20 patients were enrolled. Computed tomography-simulation and pelvic magnetic resonance images were merged to define the prostate volumes. Clinical Target Volume (CTV) was defined using the European Organisation for Research and Treatment of Cancer guidelines in consideration of the four risk categories: Low, intermediate, and high risk with or without seminal vesicles involvement, respectively. Planning Target Volume (PTV) was defined by adding 10 mm to the CTV. For each category, two treatment plans were calculated using a cobalt source or 10 MV photons. Progressive optimization was achieved by evaluating 3D dose distribution. Finally, the optimal distances between field margins and radiological landmarks (bones and rectum with contrast medium) were defined. The results were reported in tabular form. Both field margins (PTV D98% >95%) needed to adequately irradiate all patients and to achieve a similar result in 95% of the enrolled patients are reported. Using a group of patients with PCa and based on a 3D planning analysis, we propose new practical guidelines for PCa 2D-RT based on current criteria for risk category and CTV, and PTV definition.

Postoperative Hypofractionated Radiation Therapy in Prostate Carcinoma: A Systematic Review.

BACKGROUND/AIM: A systematic review on toxicity, local control (LC), overall survival (OS), and biochemical relapse-free survival (bRFS) after postoperative hypofractionated radiotherapy (HFRT) on prostate cancer (PCa) was performed. MATERIALS AND METHODS: Based on the PRISMA methodology, studies reporting clinical results after adjuvant or salvage HFRT were included. RESULTS: A total of 1,208 patients from 17 eligible studies were included. Median follow-up was 30 months. No case of severe acute gastrointestinal (GI) toxicity was recorded. Grade ≥3 acute genitourinary (GU) toxicity ranged between 0% and 3%. Different rates of grade ≥2 late GI (range=0-8.7%) and GU (range=0-66%) toxicity were recorded. Encouraging results on LC, OS, and bRFS were reported. CONCLUSION: Acute toxicity does not seem to be increased in patients receiving postoperative HFRT, but the results of late-GU toxicity are conflicting. Further prospective studies are needed before including postoperative HFRT in clinical practice.

Hypofractionated Postoperative IMRT in Prostate Carcinoma: A Phase I/II Study.

AIM: To report the outcome of hypofractionated radiotherapy after radical prostatectomy (RP) for prostate cancer (PCa) using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT). PATIENTS AND METHODS: A total of 124 patients with PCa at high risk of relapse after RP or diagnosis of biochemical relapse were included. Patients received 62.5 Gy to the prostate bed and 45 Gy to pelvic nodes in 25 fractions. Androgen-suppressive therapy was prescribed based on National Comprehensive Cancer Network risk categories. RESULTS: Median follow-up was 30 months. Only two patients (1.6%) developed grade 3 or more acute toxicity: one grade 3 skin toxicity (0.8%) and one grade 4 genitourinary toxicity (0.8%). Grade 2 acute gastrointestinal and genitourinary toxicity was recorded in 24.2% and 17.7% of patients, respectively. Five-year grade 2 or more gastrointestinal and genitourinary toxicity was 1.1% and 7.3%, respectively. Five-year biochemical relapse-free survival was 86.5%. CONCLUSION: After RP, hypofractionated IMRT-SIB demonstrated a favorable toxicity profile and encouraging results in terms of relapse-free survival.