Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long‐term hormone therapy for prostate cancer. This long‐term analysis in metastatic patients was planned for 3 years after the first results. Standard‐of‐care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC‐alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly‐diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow‐up, 329 SOC‐alone deaths (118 low‐risk, 178 high‐risk) and 244 SOC + AAP deaths (75 low‐risk, 145 high‐risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50‐0.71; P = 0.31 × 10⁻⁹) favoured SOC + AAP, with 5‐years survival improved from 41% SOC‐alone to 60% SOC + AAP. This was similar in low‐risk (HR = 0.55; 95% CI: 0.41‐0.76) and high‐risk (HR = 0.54; 95% CI: 0.43‐0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group.

Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.

Objectives To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK. Design Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire. Setting Radical radiation therapy for localised and locally advanced prostate cancer in the UK. Participants Six leading clinical oncologists and one urologist from across the UK. Interventions Rectal hydrogel spacer. Primary and secondary outcome measures None reported. Results The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens. Conclusion There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.

Background: Abiraterone acetate combined with Prednisone/Prednisolone (AA+P) and Enzalutamide (ENZ) have proven survival benefit in men with metastatic castration‐resistant prostate cancer (mCRPC) in chemotherapy‐naïve and prior chemotherapy patients. There have been no studies directly comparing the effectiveness of ENZ to AA+P in mCRPC patients.Methods: A retrospective, survival analysis study of 143 real‐world mCRPC patients (90 in AA+P and 53 in ENZ group) was conducted. Patients who started their treatment between February 2012 and May 2016 were included. The primary end point was biochemical progression‐free survival (bPFS). Secondary end points were radiological progression‐free survival (rPFS) and overall survival (OS). Toxicity data were also collected. Data were analyzed using Cox proportional hazards (PH) models, adjusting for covariates: prior radical treatment; Gleason score; prostate‐specific antigen; age; and chemotherapy naïve or not.Results: After median follow‐up of 15 months (interquartile range 7 to 23), 112 events of biochemical progression were observed (71 in AA+P and 41 in ENZ). About 41% in AA+P group and 30% patients in ENZ group received prior chemotherapy. The chance of biochemical progression was significantly lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.35 to 0.82, P = .004). There was a trend implying the chance of rPFS could be higher among ENZ patients than AA+P patients (HR 1.24, 95% CI 0.76 to 2.02, P = .4). There is no difference in OS between ENZ and AA+P patients, when adjusting for all covariates in the Cox PH model (HR 0.91, 95% CI 0.59 to 1.41, P = .7). About 38% of ENZ patients reported fatigue compared to 16% of AA+P patients, while hypertension was reported slightly more in AA+P patients.Conclusions: This study showed a statistically significant difference in bPFS, favoring ENZ, but no significant difference in rPFS or OS.

PLATFORM is a prospective, open-label, multicentre, adaptive phase II trial assessing maintenance therapy in patients with advanced HER2-negative oesophagogastric adenocarcinoma after platinum-based first-line chemotherapy. After 18 weeks of platinum-based chemotherapy, patients with response or stable disease were randomised to surveillance (4 weekly visits) or rucaparib 600 mg tablet twice daily every 28 days. The primary endpoint was progression-free survival (PFS) (prespecified P value of 0.025). Secondary endpoints were safety and overall survival (OS). Exploratory translational analyses of homologous recombination deficiency (HRD) and somatic gene profiling are also reported. A total of 125 patients were randomised (surveillance: 62, rucaparib: 63). The median follow-up was 41 months. Median PFS was 2.8 months for surveillance and 4.2 months for rucaparib [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.49-1.02, P = 0.031]. There was no difference in OS (HR 1.15, 95% CI 0.77-1.72, P = 0.247). Grade ≥3 adverse events (AEs) occurred in 23% of surveillance and 32% of rucaparib patients. Treatment-related AEs were reported in 84% of patients in the rucaparib arm; 22% of which were grade 3-4. Most frequent grade 3-4 AEs were anaemia, fatigue, infection, and neutropenia. Adequate tissue for HRD analysis was available in 51/125 (40.8%) patients (surveillance: 20, rucaparib: 31). Five patients (9.8%) were HRD-positive, 41 (80.4%) HRD-negative, and 5 (9.8%) had inconclusive results. Among HRD-positive patients, four were treated with rucaparib and had PFS durations of 2.6, 3.0, 8.3, and 10.6 months, respectively. TP53 was the most frequently detected somatic alteration, followed by SMARCA4 and ARID1A. Compared with surveillance, maintenance rucaparib following first-line chemotherapy in patients with advanced HER2-negative OGA did not significantly improve PFS with no observed difference in OS. Translational analyses were limited by small sample size, and no clear associations with clinical outcomes were identified.

Stereotactic ablative radiotherapy (SABR) is a salvage option for locally recurrent prostate cancer (LRPC); however, challenges remain. Stereotactic MRguided Adaptive Radiotherapy (SMART) permits daily adaptation, real-time tracking and automated beam gating, allowing critical organ sparing while potentially improving target coverage. Equivalent Dose in 2 Gy fraction (EQD2) calculation allows accurate organs-at-risk (OAR) dose accumulation in re-irradiation. We report safety and efficacy of daily SMART re-irradiation for LRPC, alongside an EQD2-based OAR tolerance calculation method. Salvage SMART to histologically proven non-metastatic hormone-sensitive LRPC was retrospectively analysed. Inclusion criteria included: ≥18 months post-RT, prostate-specific antigen (PSA) ≤ 30 ng/mL, PSA doubling-time > 6 months, International Prostate Symptom Score (IPSS) ≤ 19, prostate ≤ 80 cc and cT1–T3a/b.Reirradiation regimens were 30–35 Gy/5 fractions. Dose-boost and hormone therapy were allowed. Rectal spacer was recommended. Outcomes included toxicity, local control (LC), biochemical relapse-free survival (bRFS), progression free survival (PFS) and overall survival (OS). EQD2-based workflow to estimate OAR cumulative constraints was reported. Between 2019 and 2023, nineteen patients underwent salvage-SMART to whole-gland (n = 12), hemi-gland (n = 5) or seminal vesicle (n = 2) at a median 87 months (range 35–587) from first radiotherapy. All 95 delivered fractions underwent online adaptation, meeting all estimated OAR. With 21 months follow-up, acute grade 2 genitourinary (GU) toxicity was 21 % with no acute ≥ grade 3 GU or ≥ grade 2 gastrointestinal (GI) toxicity observed. Late GU grade 3 toxicity occurred in 3 patients (15.7 %). OS was 100%; bRFS 73.7%; LC 84.2%; and median-PFS was not reached. One and two-year PFS were 94.7% and 89.4%. One and two-year LC was 100%. Two contralateral intraprostatic failures followed hemi-gland treatment were observed. Daily adaptive SMART re-irradiation is a feasible, non-invasive salvage option for LRPC, combining high LC with low toxicity. Our experience supports integrating MR- guidance with an individualized EQD2-informed planning.