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In a randomized trial involving men with metastatic prostate cancer with a DNA-repair defect, rucaparib was associated with longer progression-free survival than a control medication (11.2 vs. 6.4 months).

Background and purpose: Photon-counting computed tomography (PCCT) offers enhanced image quality, including improvements in contrast, spatial resolution, and noise reduction. In radiotherapy (RT), optimal image quality is critical for accurate tumor and organ-at-risk delineation. However, reconstruction parameter selection often relies on subjective assessment. This study investigates whether quantitative image quality metrics, particularly contrast-to-noise ratio (CNR), can systematically guide PCCT tion parameter for prostate cancer RT planning. Material and methods: An anthropomorphic abdomen phantom (QRM, Móhrendorf, Germany) and five patients with prostate cancer undergoing RT were scanned on a Naeotom Alpha PCCT (Siemens Healthineers, Forchheim, Germany). Reconstructions were performed across a range of kernel types, sharpness levels, and virtual monoenergetic image (VMI) energies, with the CNR calculated for each reconstruction. Additionally, a multidisciplinary expert panel qualitatively assessed a subset of reconstructions for two patients to compare with the quantitative findings. Results: Softer kernels, particularly Br36 and Qr36, combined with lower VMI energies of 40 keV, consistently produced the highest CNR values in both phantom and patient datasets. The qualitative assessment generally supported the quantitative results, with minor deviations likely reflecting the experts' preference for a more familiar image appearance. Interpretation: Quantitative metrics such as CNR can reliably identify optimal PCCT reconstruction settings for prostate cancer RT, favoring lower VMI energies and softer reconstruction kernels. These findings were consistent across phantom and patient data and were supported by expert evaluations, indicating that a quantitative approach can effectively guide protocol development and reduce reliance on subjective image assessment.

Background Electronic collection of patient-reported outcomes (ePROs) is becoming widespread in health care, but the implementation into routine cancer care during therapy remains to be seen. Especially, little is known of the use and success of electronic reporting during active cancer treatment in fragile and comorbid patients. The aim of this study was to test the feasibility of ePRO and its incorporation into routine cancer care, measured by physician compliance, for a fragile and comorbid bladder cancer (BC) population receiving chemo- or immunotherapy. Methods All BC patients initiating treatment for locally advanced or metastatic bladder cancer at Rigshospitalet or Herlev Hospital, Denmark, were approached during an 8 month period. Exclusion criteria were patients not speaking Danish or not being signed up for electronic communication with health authorities. Enrolled patients were prompted to complete weekly ePROs from home. Patients completed the European Organisation for Research and Treatment of Cancer’s general quality of life questionnaire, QLQ-C30, and the module for muscle-invasive bladder cancer QLQ-BLM30, the Hospital Anxiety and Depression Scale, HADS, and selected items from the Patient Reported-Outcomes version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE), in total 158 questions weekly. If failing to report when prompted, patients were sent two e-mail reminders. Patients were informed that the physician would have an overview of the reported ePROs at their following clinical visits. Physicians were at all clinical visits informed to look at the ePROs in a software solution separate from the medical records. Physicians were logged to check their compliance to the task. No continuous surveillance of ePROs was established. Results Of 91 patients screened for enrolment, 19 patients (21%) were not found eligible for standard treatment, eight patients (9%) were not signed up for electronic communication with the health authorities and nine patients (10%) declined participation. Another six patients did not meet other inclusion criteria. In total 49 BC patients were enrolled, 29 initiating chemotherapy and 20 initiating immunotherapy. A total of 466 electronic questionnaires were completed. The overall adherence of the patients to complete ePROs was at an expected level for an elderly cancer population (75%) and remained above 70% until the 6th cycle of treatment. The physician’ compliance was in contrast low (0–52%) throughout the course of treatment. Conclusions Electronic reporting of PROs is feasible in a fragile and comorbid population of patients during routine active cancer treatment. Despite clear implementation strategies the physician compliance remained low throughout the study proving the need for further implementation strategies.

Background Bladder cancer (BC) patients with advanced disease have poor outcomes. The use of patient‐reported outcomes (PROs) could lead to improvements in symptom management and hence quality of life (QoL). The aim of this study is to report correlations between selected PROs and QoL and thus to present symptoms that influence QoL. Identification of these symptoms during treatment can lead to earlier symptom management and thus secure improvements in QoL. Methods BC patients in chemo‐ or immunotherapy for locally advanced or metastatic disease reported weekly PROs for the duration of their treatment. The PROs included EORTC QLQ‐C30 and QLQ‐BLM30 and 45 selected PRO‐CTCAE items. Spearman's correlation analysis was performed for all PRO‐CTCAE items and QLQ‐C30 global QoL and subdomains. Results In this study, 78 BC patients reported 724 questionnaires. Spearman's analysis showed significant correlations between almost all PRO‐CTCAE items and the expected domain of QoL. The PRO‐CTCAE items with the strongest correlations with QoL were anxiety (F, frequency item) and emotional function (rs = −0.603, P < .0001), concentration (S, severity item) and cognitive function (rs = −0.704, P < .0001), discouraged (F) and emotional function (rs = −0.659, P < .0001), fatigue (S) and role function (rs = −0.659, P < .0001) and sad (F) and emotional function (rs = −0.711, P < .0001). The weakest correlations were found for the PRO‐CTCAE items urinary frequency, incontinence and urge, all with variations in the direction and significance of the correlations. Conclusions This study delivers information on which PROs may influence QoL for patients in clinical trials or daily clinic. Psychological issues have a strong impact on QoL and should be dealt with during treatment to secure the best possible QoL for BC patients. For bladder cancer patients, psychological items have a strong impact on the quality of life while urinary items have a weak impact on the quality of life. Toxicity reporting from clinical trials and supportive care in daily practice may be incomplete and not reflective of the full picture of symptomatology for bladder cancer patients.

BackgroundEnzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC), but different mechanisms of action. The aim was to compare patient-reported health-related quality of life (HRQoL) in men treated with enzalutamide vs AAP for mCRPC.MethodsWe systematically reviewed the literature in June 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Patient-reported outcomes (PROs) until the last follow-up were summarised in a narrative synthesis. Short-term changes (12 weeks) in HRQoL, measured by the Functional Assessment of Cancer Therapy-Prostate total score (FACT-P), were compared between treatment groups and were analysed for enzalutamide and AAP in separate meta-analyses. Higher FACT-P scores indicate better HRQoL.ResultsEight studies were included in the systematic review, four of which were randomised clinical trials (RCTs) eligible for the meta-analyses. The meta-analyses showed mean within-subject FACT-P changes from baseline to week 12 of −1.3 points (95% confidence interval [CI] −2.7; 0.1) for enzalutamide and 4.7 points (95% CI −0.1; 9.6) for AAP.One RCT and three non-randomised studies directly compared enzalutamide with AAP. The RCT showed better short-term HRQoL for AAP (6.8 FACT-P-points, 95% CI 1.7; 11.8) and better long-term HRQoL for AAP in men ≥75 years (7.35 FACT-P-points, 95% CI 2.59; 12.11). The non-randomised studies showed no difference in long-term HRQoL but had all a serious risk of bias.Limitations of the included studies include that the PRO in the included trials were inconsistently reported and that only one study defined the HRQoL measures in their published protocol.ConclusionsAAP seems to be associated with better short-term HRQoL than enzalutamide. This difference was not apparent at longer follow-up, but the long-term studies had serious risks of bias.

IntroductionImmunotherapy with checkpoint inhibitors (CPIs) has revolutionised cancer treatment but has no convincing effect in metastatic castration-resistant prostate cancer (mCRPC). It has been suggested that a combination of CPI and hypofractionated stereotactic body radiotherapy (SBRT) may work synergistically, and recent trials have supported this. We hypothesise that adding SBRT to CPI treatment can improve response rates in patients with mCRPC.Methods and analysisThe CheckPRO trial is an open-label, randomised, two-stage, phase II trial. We aim to enrol and randomise 80 evaluable patients with mCRPC who progressed following ≥2 lines of treatment. Enrolment started in November 2019 with 38 months expected enrolment period. The participants receive treatment for 52 weeks including four cycles of ipilimumab and nivolumab with or without concomitant SBRT (24 Gray in three fractions) to a single soft tissue or bone metastasis, followed by 10 cycles of nivolumab. Participants are followed until progression, death, or for 12 months after the end of treatment.Co-primary endpoints are the objective response rate and prostate-specific antigen (PSA) response rate. Secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life and overall survival. Exploratory endpoints include translational analyses of tumour biopsies and consecutive blood samples. Biopsies from metastatic sites are collected at baseline, before the third treatment and at the end of treatment. Blood sampling for immune monitoring and circulating tumour DNA is performed consecutively at baseline and every radiographic assessment.Ethics and disseminationThis study follows the Helsinki Declaration and is approved by the Danish Ethics Committee System (journal no. H-19016100). All participants must receive written and oral information and provide a signed informed consent document prior to inclusion. The study results will be published in an international peer-review journal.Trial registration numberEudraCT number: 2018-003461-34. clinicaltrials.gov ID NCT05655715.

Background Selection of specific patient-reported outcomes (PROs) for cancer patients requires careful consideration to the purpose and population at aim. Here we report the process of choosing which items to include in a bladder cancer population in chemo- or immunotherapy based on the Patient-Reported Outcomes Version of the Common Terminology Criteria of Adverse Events (PRO-CTCAE). Methods Initial PRO-CTCAE symptoms were chosen through 1) medical record audit 2) patient interviews 3) summary of product characteristics from European Medicines Agency and Food and Drug Administration for the applied chemotherapies, and 4) toxicity reporting from Phase 2 and 3 trials for immunotherapies applied in patients with urothelial cancer. The selected questions were applied in a prospective cohort of 78 bladder cancer patients receiving chemo- or immunotherapy at Rigshospitalet and Herlev Hospital, Denmark. Symptoms tested in this population were selected for the final module if they appeared in ≥3 of the following groupings a) the most prevalent PRO-CTCAE symptoms grade ≥ 2 overall during treatment b) the PRO-CTCAE symptoms reported in conjunction with hospital admissions or mentioned in focus group interviews discussing which symptoms were prevalent in this patient group with specialized c) nurses or d) physicians. The authors also included symptoms in the final module if they were present in two of the above groups and defined as actionable by clinicians. Results From the initial selection of PRO-CTCAE symptoms, a total of 45 PRO-CTCAE symptoms explored by 84 PRO-CTCAE questions were retrieved. Through the second selection process based on the described criteria, the study group agreed on 15 PRO-CTCAE symptoms explored by 30 PRO-CTCAE items to be appropriate and relevant for the bladder population during medical oncological treatment. Conclusions The selection of disease specific PROs in a bladder cancer population was feasible. The process revealed several steps of selection needed in order to reach a final module for clinical application.

Background Patient-reported outcomes (PROs) are getting widely implemented, but little is known of the impact of applying PROs in specific cancer diagnoses. We report the results of a randomized controlled trial (RCT) of the active use of PROs in patients with locally advanced or metastatic bladder cancer (BC) undergoing medical oncological treatment (MOT) with focus on determining the clinical effects of using PROs during chemo- or immunotherapy compared to standard of care. Methods We recruited patients from four departments of oncology from 2019 to 2021. Inclusion criteria were locally advanced or metastatic BC, initiating chemo- or immunotherapy. Patients were randomized 1:1 between answering selected PRO-CTCAE questions electronically once weekly with a built-in alert-algorithm instructing patients of how to handle reported symptoms as a supplement to standard of care for handling of side effects (intervention arm (IA)) vs standard procedure for handling of side effects (control arm (CA)). No real-time alerts were sent to the clinic when PROs exceeded threshold values. Clinicians were prompted to view the completed PROs in the IA at each clinical visit. The co-primary clinical endpoints were hospital admissions and treatment completion rate. Secondary endpoints were overall survival (OS), quality of life (EORTC’s QLQ-C30 and QLQ-BLM30) and dose reductions. Results 228 patients with BC were included, 76% were male. 141 (62%) of the patients had metastatic disease. 51% of patients in the IA completed treatment vs. 56% of patients in the CA, OR 0.83 (95% CI 0.47–1.44, p  = 0.51). 41% of patients in the IA experienced hospitalization vs. 32% in the CA, OR 1.48 (95% CI 0.83–2.65, p  = 0.17). OS was comparable between the two arms (IA: median 22.3mo (95% CI 17.0-NR) vs. CA: median 23.1mo (95% CI 17.7-NR). Patient and clinician compliance was high throughout the study period (80% vs 94%). Conclusions This RCT did not show an effect of PRO on completion of treatment, hospitalizations or OS for BC patients during MOT despite a high level of patient and clinician compliance. The lack of real-time response to alerts remains the greatest limitation to this study.

IntroductionEnzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with enzalutamide and AAP yields similar overall survival and radiographic progression-free survival in phase III trials. Thus, treatment selection relies on patient choice, cost and side effects. The aim of this randomised trial is to investigate differences in fatigue, health-related quality of life (HRQoL) and metabolic side effects in men with mCRPC treated with first-line enzalutamide versus AAP.Methods and analysisIn this ongoing open-label randomised (1:1) clinical trial, enzalutamide is compared with AAP as first-line treatment for men with mCRPC. The primary endpoint is fatigue assessed with the questionnaire Functional Assessment of Chronic Illness Therapy-Fatigue version 4. Secondary endpoints are changes in body composition (ie, fat mass, visceral adipose tissue, subcutaneous adipose tissue and lean body mass assessed with dual energy X-ray absorptiometry), glucose metabolism assessed with a 2-hour oral glucose tolerance test, serum lipids, blood pressure and HRQoL assessed with the questionnaire Functional Assessment of Cancer Therapy-Prostate (FACT-P). All study endpoints are assessed at baseline and 12-week postintervention. Blood and urine samples are collected at baseline and at time of progression on allocated treatment for future investigation of predictive and prognostic biomarkers in prostate cancer treatment. The planned sample size is 170 participants. All participants are recruited from Herlev and Gentofte Hospital, Denmark. Estimated last patient’s last visit is February 2020.Ethics and disseminationThe study received project approval from the National Committee on Health Research Ethics and Danish Data Protection Agency and Danish Medicines Agency (EudraCT no.: 2017-000027-99). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums.Trial registration numberClinicaltrialsregister.eu (2017-000099-27).

The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7–10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60–68). Median follow-up was 4·9 years (IQR 3·0–6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81–1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58–1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3–4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.