Moderate hypofractionated radiotherapy for prostate cancer: 3-year toxicity results of a multicentre randomized phase 3, non-inferiority trial.

BACKGROUND AND PURPOSE: Moderate hypofractionated radiotherapy (HFRT) is a standard treatment for prostate cancer patients. We compared 2 moderate HFRT regimens, with a biologically equivalent dose of 80 Gy in 2 Gy fractions, with a modest simultaneous integrated boost to the dominant intraprostatic lesion. MATERIAL AND METHODS: This is a multicenter, non-inferiority, randomized phase 3 trial with acute toxicity as the primary endpoint, comparing: 56 Gy in 4 weeks (16x3.5 Gy, 4 days/week, Arm A) with 67 Gy in 5 weeks (25x2.68 Gy, 5 days/week, Arm B). The H0 hypothesis is that both regimens are equivalent in terms of acute grade ≥ 2 gastro-intestinal toxicity, defined as a difference in acute grade ≥ 2 gastro-intestinal toxicity of ≤ 10 %. Here we report on acute and late toxicity. RESULTS: We included 170 patients in Arm A and 172 patients in Arm B. The median follow-up time for all patients was 42 months. Acute grade ≥ 2 gastrointestinal toxicity was reported by 24 % of patients in both groups. Acute grade 2 and 3 urinary toxicity was observed in 52 % and 9 % of patients in Arm A and 53 % and 7 % in Arm B. Late grade 2 and grade ≥ 3 gastrointestinal toxicity occurred in 19 % and 4 % of patients in Arm A compared with 15 % and 4 % in Arm B. Late grade 2 and grade ≥ 3 urinary toxicity was observed in 37 % and 10 % of patients in Arm A and 36 % and 6 % in Arm B. CONCLUSION: This analysis confirms that both HFRT regimens are safe and equivalent in terms of acute grade ≥ 2 gastrointestinal toxicity.

Treatment of patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) in Belgium: a real world data analysis.

INTRODUCTION: Abiraterone acetate + prednisone (AAP) and docetaxel have proven their efficacy in the treatment of patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) in clinical trials. However, real-world data are scarce. The goal of this study is to evaluate real-world data on the efficacy and safety of these therapies in mHSPC patients. PATIENTS AND METHODS: Records of 93 patients from 21 different centres were retrospectively reviewed. Primary and secondary endpoints were radiographic and PSA progression-free survival (RPFS - PSA-PFS) and cancer specific and overall survival (CSS - OS), respectively. Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Differences in oncological outcome and AEs were evaluated between three treatment groups: ADT only (N=26) - ADT + AAP (N=48) - ADT + docetaxel (N=19). Survival analysis was performed using Kaplan-Meier statistics. RESULTS: Median RPFS was 13 months (95% confidence interval [CI]: 9-17) for ADT only, 21 months (95% CI: 19-23) for ADT + AAP and 12 months (95% CI: 11-14) for ADT + docetaxel (p = 0.004). The 1-year PSA-PFS, CSS and OS were 73.5%, 90.7% and 88.7%, respectively, with no significant differences between the three groups. Adverse events of grade 3 or higher were not observed more frequently. CONCLUSION: Retrospective real-world data show a significantly longer RPFS for mHSPC patients treated with ADT + AAP compared to ADT only or ADT + docetaxel at short-term follow-up. This can aid in counselling of mHSPC patients in daily clinical practice.

Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial.

BACKGROUND: High-risk muscle-invasive bladder cancer (MIBC) has a poor prognosis. Old trials showed that external beam radiotherapy (EBRT) after radical cystectomy (RC) decreases the incidence of local recurrences but induces severe toxicity. OBJECTIVE: To evaluate the toxicity and local control rate after adjuvant EBRT after RC delivered with volumetric arc radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: This is a multicentric phase 2 trial. From August 2014 till October 2020, we treated 72 high-risk MIBC patients with adjuvant EBRT after RC. High-risk MIBC is defined as ≥pT3-MIBC ± lymphovascular invasion, fewer than ten lymph nodes removed, pathological positive lymph nodes, or positive surgical margins. INTERVENTION: Patients received 50 Gy in 25 fractions with intensity-modulated radiotherapy to the pelvic lymph nodes ± cystectomy bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is acute toxicity. We report on local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS), and bladder cancer-specific survival (BCSS). RESULTS AND LIMITATIONS: The median follow-up is 18 mo. Forty-two patients (61%) developed acute grade 2 gastrointestinal (GI) toxicity. Four patients (6%) had acute grade 3 GI toxicity. One patient had grade 5 diarrhea and vomiting due to obstruction at 1 mo. Two-year probabilities of developing grade ≥3 and ≥2 GI toxicity were 17% and 76%, respectively. Urinary toxicity, assessed in 17 patients with a neobladder, was acceptable with acute grade 2 and 3 urinary toxicity reported in 53% (N = 9) and 18% (N = 3) of the patients, respectively. The 2-yr LRFR is 83% ± 5% and the 2-yr CRFS rate is 43% with a median CRFS time of 12 mo (95% confidence interval: 3-21 mo). Two-year OS and BCSS are 52% ± 7% and 62% ± 7%, respectively. Shortcomings are the nonrandomized study design and limited follow-up. CONCLUSIONS: Adjuvant EBRT after RC can be administered without excessive severe toxicity. PATIENT SUMMARY: In this report, we looked at the incidence of toxicity and local control after adjuvant external beam radiotherapy (EBRT) following radical cystectomy (RC) in high-risk muscle-invasive bladder cancer patients. We found that adjuvant EBRT was feasible and resulted in good local control. We conclude that these data support further enrollment of patients in ongoing trials to evaluate the place of adjuvant EBRT after RC.

Cognitive factors influencing treatment decision-making in patients with localised prostate cancer: development of a standardised questionnaire.

BACKGROUND: Men diagnosed with localised prostate cancer have to make a well-informed treatment choice between (robot-assisted) radical prostatectomy, external beam radiotherapy and, in selected cases, brachytherapy and active surveillance. We developed and validated a questionnaire to determine the cognitive reasons motivating this choice. MATERIALS AND METHODS: The Prostate Cancer Decision-Making Questionnaire (PC-DMQ) was designed in-house and validated through the Delphi method. Finally, we tested the questionnaire in a cohort of 24 men, recently diagnosed with localised PC, before undergoing RARP (n = 16), EBRT (n = 6), brachytherapy (n = 1) or active surveillance (n = 1). RESULTS: The experts reached consensus after three rounds. In the patient cohort, 75% of men undergoing RARP chose this treatment because 'it provides the best chance of cure'. Reasons to choose EBRT were not as explicit: 33.3% chose this treatment because 'it provides the best chance of cure' and 33.3% because 'the maintenance of potency is important to them'. CONCLUSIONS: The PC-DMQ is a comprehensive and standardised tool that allows further research into cognitive factors that influence treatment decision-making in patients with localised PC.

Congenital penile pathology is associated with abnormal development of the dartos muscle: a prospective study of primary penile surgery at a tertiary referral center.

PURPOSE: Pathophysiological mechanisms leading to chordee in patients with hypospadias and to the hidden state of buried penis in the prepubic fat remain unclear. Resection of dartos tissue usually makes the penis straight in patients with hypospadias and corrects it in those with buried penis, suggesting a common pathophysiology related to dartos tissue. MATERIALS AND METHODS: Tissue samples from 113 children undergoing primary penile surgery for hypospadias (94 patients), epispadias (1) or buried penis (18) were collected between November 2011 and September 2013. Tissue samples from 79 children undergoing circumcision for nonmedical reasons served as controls. All samples were stained with smooth muscle actin and analyzed by the same pathologist, who was blinded to indication for surgery. Chi-square and Fisher exact tests were applied. RESULTS: Three different dartos tissue patterns were observed. Pattern I (normal) consisted of smooth muscle fibers of dartos tissue organized in a parallel configuration in the subcutaneous tissue. Pattern II was characterized by poorly developed and hypotrophic smooth muscle fibers. Pattern III was determined by randomly distributed smooth muscle fibers in the subcutaneous tissue, without parallel configuration. Pattern I was observed in 45 circumcision specimens (64%). Of buried penis cases 78% were considered abnormal (pattern II in 4 cases and III in 10, p = 0.001). Of hypospadias cases 70% were considered abnormal (pattern II in 31 cases, III in 32, and mixed II and III in 3, p < 0.001). The only epispadias case was designated pattern II. CONCLUSIONS: Congenital penile pathology (hypospadias, buried penis) is associated with structural anomalies in dartos tissue. Further research is needed to unveil the pathophysiology of the condition.