Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis.

BACKGROUND: Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: To systematically review trials of prostate radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known. We searched extensively for eligible trials and asked investigators when results would be available. We could then anticipate that a definitive meta-analysis of the effects of prostate radiotherapy was possible. We obtained prepublication, unpublished, and harmonised results from investigators. INTERVENTION: We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for the effects of prostate radiotherapy on survival, progression-free survival (PFS), failure-free survival (FFS), biochemical progression, and subgroup interactions were combined using fixed-effect meta-analysis. RESULTS AND LIMITATIONS: We identified one ongoing (PEACE-1) and two completed (HORRAD and STAMPEDE) eligible trials. Pooled results of the latter (2126 men; 90% of those eligible) showed no overall improvement in survival (HR=0.92, 95% confidence interval [CI] 0.81-1.04, p=0.195) or PFS (HR=0.94, 95% CI 0.84-1.05, p=0.238) with prostate radiotherapy. There was an overall improvement in biochemical progression (HR=0.74, 95% CI 0.67-0.82, p=0.94×10-8) and FFS (HR=0.76, 95% CI 0.69-0.84, p=0.64×10-7), equivalent to ?10% benefit at 3yr. The effect of prostate radiotherapy varied by metastatic burden-a pattern consistent across trials and outcome measures, including survival (<5, ?5; interaction HR=1.47, 95% CI 1.11-1.94, p=0.007). There was 7% improvement in 3-yr survival in men with fewer than five bone metastases. CONCLUSIONS: Prostate radiotherapy should be considered for men with mHSPC with a low metastatic burden. PATIENT SUMMARY: Prostate cancer that has spread to other parts of the body (metastases) is usually treated with hormone therapy. In men with fewer than five bone metastases, addition of prostate radiotherapy helped them live longer and should be considered

Local therapy in primary metastatic prostate cancer Lokale behandeling bij het primair gemetastaseerd prostaatcarcinoom

A substantial proportion of patients with prostate cancer have metastases at the time of diagnosis. Recent literature suggests that local radiotherapy to the prostate should be advised in these patients, provided they have a low metastasic burden (as defined by the CHAARTED criteria). This article discusses the available literature

Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial

Background: A survival benefit was demonstrated for patients with low-volume metastatic prostate cancer (mPCa) when local radiotherapy was added to androgen deprivation therapy (ADT). Objective: To determine the effect of ADT combined with external beam radiotherapy (EBRT) to the prostate on health-related quality of life (HRQoL) of patients with primary bone mPCa. Design, setting, and participants: The HORRAD trial is a multicentre randomised controlled trial recruiting 432patients with primary bone mPCa between 2004 and 2014. Intervention: Patients were randomised to ADT with EBRT or to ADT alone. Outcome measurements and statistical analysis: Patients completed two validated HRQoL questionnaires (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core Module (QLQ-C30) and EORTC Quality of Life Questionnaire Prostate Module [QLQ-PR25]) at baseline and at 3, 6, 12, and24 mo after the initiation of treatment. The effect of both treatments was evaluated based on mixed-effect models. Results and limitations: Patient characteristics and HRQoL scores at baseline were similar in both arms. At baseline, 98% of patients completed the questionnaires, compared with 58% at 24 mo. Patients reported significantly more diarrhoea (difference between the groups 10.8; 95% confidence interval [CI] 7.3–14.2), bowel symptoms (4.5; 95% CI 2.1–6.8), and urinary symptoms (11.9; 95% CI 8.9–14.8) after EBRT and ADT compared with ADT alone (all between-arm difference p < 0.001). Urinary complaints levelled at 6 mo. At 2 yr, only bowel symptom scores were significantly different (8.0; 95% CI 4.8–11.1, p ≤ 0.001), but 68% of patients in the radiotherapy group did not report clinically relevant worsening of their bowel symptom scores. Conclusions: Patients with bone mPCa reported temporary modest urinary and bowel symptoms after combined treatment with EBRT of the prostate and ADT compared with ADT alone. For some patients (22%), deterioration of bowel functions remains at 2 yr, whereas general HRQoL does not deteriorate. Patient summary: This study investigated the effect of radiotherapy to the prostate added to hormonal therapy on patient-reported health-related quality of life (HRQoL) in patients with primary bone metastatic prostate cancer. Most patients reported only temporary urinary and bowel symptoms. In 22% of patients, bowel symptoms remained at 2 yr, whereas general HRQoL did not deteriorate. Patients with bone metastatic prostate cancer reported temporary modest urinary and bowel symptoms after combined treatment with prostate radiotherapy and hormonal therapy compared with hormonal therapy alone. Both treatments did not affect global health-related quality of life

Patient-reported Quality of Life in Patients with Primary Metastatic Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate in a Prospective Randomised Clinical Trial; Data from the HORRAD Trial

Background: A survival benefit was demonstrated for patients with low-volume metastatic prostate cancer (mPCa) when local radiotherapy was added to androgen deprivation therapy (ADT). Objective: To determine the effect of ADT combined with external beam radiotherapy (EBRT) to the prostate on health-related quality of life (HRQoL) of patients with primary bone mPCa. Design, setting, and participants: The HORRAD trial is a multicentre randomised controlled trial recruiting 432patients with primary bone mPCa between 2004 and 2014. Intervention: Patients were randomised to ADT with EBRT or to ADT alone. Outcome measurements and statistical analysis: Patients completed two validated HRQoL questionnaires (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Core Module (QLQ-C30) and EORTC Quality of Life Questionnaire Prostate Module [QLQ-PR25]) at baseline and at 3, 6, 12, and24 mo after the initiation of treatment. The effect of both treatments was evaluated based on mixed-effect models. Results and limitations: Patient characteristics and HRQoL scores at baseline were similar in both arms. At baseline, 98% of patients completed the questionnaires, compared with 58% at 24 mo. Patients reported significantly more diarrhoea (difference between the groups 10.8; 95% confidence interval [CI] 7.3–14.2), bowel symptoms (4.5; 95% CI 2.1–6.8), and urinary symptoms (11.9; 95% CI 8.9–14.8) after EBRT and ADT compared with ADT alone (all between-arm difference p < 0.001). Urinary complaints levelled at 6 mo. At 2 yr, only bowel symptom scores were significantly different (8.0; 95% CI 4.8–11.1, p ≤ 0.001), but 68% of patients in the radiotherapy group did not report clinically relevant worsening of their bowel symptom scores. Conclusions: Patients with bone mPCa reported temporary modest urinary and bowel symptoms after combined treatment with EBRT of the prostate and ADT compared with ADT alone. For some patients (22%), deterioration of bowel functions remains at 2 yr, whereas general HRQoL does not deteriorate. Patient summary: This study investigated the effect of radiotherapy to the prostate added to hormonal therapy on patient-reported health-related quality of life (HRQoL) in patients with primary bone metastatic prostate cancer. Most patients reported only temporary urinary and bowel symptoms. In 22% of patients, bowel symptoms remained at 2 yr, whereas general HRQoL did not deteriorate. Patients with bone metastatic prostate cancer reported temporary modest urinary and bowel symptoms after combined treatment with prostate radiotherapy and hormonal therapy compared with hormonal therapy alone. Both treatments did not affect global health-related quality of life

Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial

Background: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. Objective: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. Design, setting, and participants: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20 ng/ml and primary bone mPCa on bone scan between 2004 and 2014. Intervention: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). Outcome measurements and statistical analysis: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. Results and limitations: Median PSA level was 142 ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4–49.6) in the radiotherapy group and 43 mo (95% CI: 32.6–53.4) in the control group (p = 0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70–1.14; p = 0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8–18.2), compared with 12 mo (95% CI: 10.6–13.4) in the control group. The crude HR (0.78; 95% CI: 0.63–0.97) was statistically significant (p = 0.02). Conclusions: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. Patient summary: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. Twitter summary: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival. In the current randomised controlled trial, there is no improvement in overall survival when comparing androgen deprivation therapy alone to androgen deprivation therapy with concurrent radiotherapy to the prostate in patients with primary bone metastatic prostate cancer

Cancer detection and complications in transperineal prostate biopsy, with antibiotics only when indicated

Objectives: To describe the prostate cancer (PCa) detection rate, including clinically significant prostate cancer (csPCa), in a large cohort of patients who underwent transperineal ultrasonography-guided systematic prostate biopsy (TPB-US) using a probe-mounted transperineal access system, with magnetic resonance imaging (MRI) cognitive fusion in case of a Prostate Imaging–Reporting and Data System grade 3–5 lesion, under local anaesthesia in an outpatient setting. Additionally, to compare the incidence of procedure-related complications with a cohort of patients undergoing transrectal ultrasonography-guided (TRB-US) and transrectal MRI-guided biopsies (TRB-MRI). Patients and Methods: This was an observational cohort study in men who underwent TPB-US prostate biopsy in a large teaching hospital. For each participant, prostate-specific antigen level, clinical tumour stage, prostate volume, MRI parameters, number of (targeted) prostate biopsies, biopsy International Society of Uropathology (ISUP) grade and procedure-related complications were assessed. csPCa was defined as ISUP grade ≥2. Antibiotic prophylaxis was only given in those with an increased risk of urinary tract infection. Results: A total of 1288 TPB-US procedures were evaluated. The overall detection rate for PCa in biopsy-naive patients was 73%, and for csPCa it was 63%. The incidence of hospitalization was 1% in TPB-US (13/1288), compared to 4% in TRB-US (8/214) and 3% in TRB-MRI (7/219; P = 0.002). Conclusions: Contemporary combined systematic and target TPB-US with MRI cognitive fusion is easy to perform in an outpatient setting, with a high detection rate of csPCa and a low incidence of procedure-related complications