Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

BACKGROUND: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade. STUDY DESIGN: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden. ENDPOINTS: The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa-specific survival, metastasis-free survival, role-functioning scale (EORTC quality of life questionnaire 30-item core), urinary irritative/obstructive scale (26-item Expanded Prostate Cancer Index Composite [EPIC-26]), bowel scale (EPIC-26), intervention-free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality-adjusted life-years (QALYs), and mean total healthcare costs. PATIENTS AND METHODS: A total of 980 men (aged ≥75 years) with non-metastatic, high-risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini-COG© brief cognitive test. Participants identified by G8 as 'fit' or 'frail' will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years. TRIAL REGISTRATION: Ethics approval has been granted in Norway (457593), Denmark (H-22051998), Finland (R23043) and Sweden (Dnr 2023-05296-01). The trial is registered on Clinicaltrials.org (NCT05448547).

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.

The Multicenter, Randomized, Phase 2 PEACE V-STORM Trial: Defining the Best Salvage Treatment for Oligorecurrent Nodal Prostate Cancer Metastases.

Optimal local treatment for nodal oligorecurrent prostate cancer is unknown. The randomized phase 2 PEACE V-STORM trial will explore the best treatment approach in this setting. Early results on the acute toxicity profile are projected to be published in quarter 3, 2021.

Weekly versus 3-weekly cabazitaxel for the treatment of castration-resistant prostate cancer: A randomised phase II trial (ConCab).

AIM: Patients treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) may experience dose delays and reductions or terminate treatment because of toxicity. A lower and more frequent dose of cabazitaxel could improve dose intensity. PATIENTS AND METHODS: This prospective, multi-center, phase II study randomly assigned 101 patients to Arm A, cabazitaxel Q3W, 25 mg/m2 or Arm B, Q1W, 10 mg/m2 5 of 6 weeks. The primary end-point was dose intensity, and we hypothesised that the experimental arm (Arm B) would result in a 20% absolute increase in the relative cumulative dose by week 18. Secondary end-points were overall survival (OS), progression-free survival (PFS), pain progression, radiological and prostate-specific antigen (PSA) response rates, quality of life (Functional Assessment of Cancer Therapy Prostate) and tolerability. RESULTS: Median doses of cabazitaxel were 276 mg (45-320) and 257 mg (20-330) in Arms A and B, respectively, at week 18 (p = 0.13). More patients in Arm B stopped treatment because of toxicity. Median PFS in Arms A and B were 6.0 and 6.4 months (hazard ratio [HR] 0.73, 95% confidence interval [CI]: 0.47-1.13, p = 0.156) and for OS, 14.6 and 15.6 months (HR 0.95, CI: 0.58-1.58, p = 0.85), respectively. PSA responses ≥50% were seen in 52% and 46% of patients in Arms A and B, respectively. A higher incidence of febrile neutropenia was observed in the standard arm (10 events versus 1, p < 0.008). A grade V febrile neutropenia occurred in Arm A. Low-grade haematuria was more prevalent with weekly cabazitaxel (15 events versus 5, p = 0.003). Three patients in Arm B experienced clinically significant inflammation of the ureters. A toxicity is not previously described for cabazitaxel. CONCLUSION: Weekly cabazitaxel reduces the incidence of febrile neutropenia but does not increase the dose intensity compared with the standard therapy. Cabazitaxel has clinical meaningful efficacy in heavily pre-treated patients with mCRPC.