In cases of biochemical recurrence (BCR) after radical prostatectomy, salvage radiotherapy (RT) is a well-established standard-of-care treatment. Stereotactic body radiotherapy (SBRT) may offer a shorter treatment duration and favorable radiobiological characteristics, but evidence in the postoperative setting remains limited. This trial aims to compare genitourinary and gastrointestinal patient-reported outcomes after salvage SBRT with standard-of-care schedules. Two-hundred eighty-four patients with persistent or rising PSA levels after radical prostatectomy will be randomized in a 1:1 ratio to receive either a normofractionated or mildly hypofractionated RT schedule (64–70 Gy in 32–35 fractions or 52.5 Gy in 20 fractions, Arm A), or a SBRT schedule (32 Gy in 5 fractions, Arm B). Randomization will be stratified by study center and by the investigator’s treatment choices regarding standard-of-care androgen deprivation therapy (ADT; 6 months) and whole-pelvis radiotherapy (WPRT). The co-primary endpoints are the two-year change from baseline in the urinary and bowel domains of the EPIC-26 questionnaire. Secondary endpoints include patient-reported outcomes across all EPIC-26 domains, IPSS and EQ-5D-5 L scores up to 5 years, physician-reported toxicity according to CTCAE v5.0, biochemical progression-free survival (bPFS), distant metastasis-free survival (dmFS), local and regional control, overall survival (OS), cost-utility analysis based on EQ-5D-5 L compared with RT and transportation costs during treatment, and the lymphocyte nadir relative to baseline. This is one of the first multicenter randomized phase II/III trials designed to demonstrate that SBRT does not increase patient-reported gastrointestinal (GI) or genitourinary (GU) symptoms compared with standard-of-care (SOC) fractionations at the 2-year time point. ClinicalTrials.gov ID NCT06523634. Date of registration: May 28, 2024.

Evidence describing outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) in men who previously underwent transurethral resection of the prostate (p-TURP) is limited. This study aimed to characterize perioperative performance, cancer control, and the pattern of urinary continence recovery (UCR) in this subgroup. We analyzed all RS-RARP procedures conducted by a single high-volume surgeon at a European tertiary center from April 2016 till December 2023. Patients were categorized according to the presence or absence of prior p-TURP. To minimize baseline differences, a 5:1 propensity score matching model was used. Among 542 men who met the inclusion criteria, 29 (17

Background and purpose:Traditional dose-volume histogram (DVH) metrics used in radiotherapy plan evaluation lack spatial information and are sensitive to organ volume variations. This study investigated the use of Dose Gradient Curves (DGCs) as a robust, volume-independent alternative for assessing organ sparing in prostate stereotactic body radiation therapy (SBRT). Materials and methods:Treatment plans of 154 prostate cancer patients were retrospectively analysed. A benchmark set of 20 high-quality plans was established, and average DVH (aDVH) and DGC (aDGC) curves were derived for the bladder and anorectum. Plan quality of the remaining 134 plans was assessed using aDVH, aDGC, and expert-reviewed ground truth. A ΔAUC-based classifier was developed to automatically detect suboptimal organ sparing. The robustness of benchmark set size was evaluated by comparing subsets of five plans with extreme organ volumes. Results:The inclusion of dose-gradient information improved accuracy and precision compared to DVH-based methods. For the bladder, DGC analysis achieved 99% accuracy and precision, compared to 87% and 94% for DVH. For the anorectum, DGC yielded 97% accuracy and 100% precision. The ΔAUC classifier achieved F1 scores of 97.1% (bladder) and 89.7% (anorectum). Reducing the benchmark set to five plans did not significantly affect DGC-based evaluations, unlike DVH-based assessments. Conclusions:DGC-based plan evaluation offers a reliable and volume-independent method for assessing organ sparing in prostate SBRT. It enabled automated detection of suboptimal plans and remained robust even with reduced benchmark sizes. Further investigation prior to clinical implementation is required.

For prostate cancer patients with metachronous nodal oligorecurrences detected by positron emission tomography, the randomized phase 2 PEACE V-STORM trial (NCT03569241) demonstrated that, compared with metastasis-directed therapy (MDT), elective nodal pelvic radiotherapy (ENRT) in combination with 6 mo of androgen deprivation therapy (ADT) improved locoregional disease control and metastasis-free survival. In the 190 evaluable patients (MDT: 97 and ENRT: 93) of the 196 randomized in the study, health-related quality of life (HRQoL) was assessed by European Organization for Research and Treatment of Cancer QLQ-C-30 and QLQ-PR-25 questionnaires over a 4-yr period as a part of a statistically defined quality of life analysis. During a median follow-up of 50 mo (interquartile range 42-58), QLQ-C30 scores showed no significant differences between MDT and ENRT, except for worse physical functioning at month 24 in the ENRT group (mean decline -7.7 vs -1.3) and worse emotional functioning at month 12 in the MDT group (mean decline 5.8 vs -0.4, p = 0.034). No significant differences in QLQ-PR25 scores were observed, except slightly better bowel symptoms at 18 mo for ENRT, but with no difference before or after. The decline in sexual activity and increase in ADT-related symptoms during the first 6 mo were comparable between arms, returning to baseline by month 12. Consistent with physician-reported treatment-related adverse events, HRQoL analyses show no significant differences between ENRT and MDT.

Robot-assisted radical prostatectomy (RARP) is a widely adopted and effective treatment for localized prostate cancer. The Retzius-sparing approach (RS-RARP) has been shown to significantly improve early urinary continence recovery while maintaining comparable long-term oncological outcomes relative to the anterior approach. However, the impact of body mass index (BMI) on RS-RARP outcomes remains insufficiently investigated. The present study aimed to address this gap. A retrospective analysis was conducted on 596 patients who underwent RS-RARP between April 2016 and December 2023, including 197 normal-weight, 287 overweight, and 112 obese individuals. Perioperative, oncological, and functional outcomes were assessed. Estimated blood loss was significantly higher in obese patients. No statistically significant differences in urinary continence rates were observed at any time point. Immediate continence rates were 77

Robot-assisted radical prostatectomy using the Retzius-sparing approach (RS-RARP) is increasingly adopted, yet evidence regarding outcomes in men aged ≥ 75 years remains extremely limited. This study evaluated perioperative, oncological, and functional outcomes of RS-RARP in elderly patients. A total of 608 men who underwent RS-RARP between 2016 and 2023 were included. Patients were divided into two groups: <75 years (n = 548) and ≥ 75 years (n = 60). Preoperative characteristics, surgical parameters, complications, pathological findings, and continence status up to 12 months were compared. Men aged ≥ 75 years presented more often with larger prostates, higher biopsy ISUP grades, and more intermediate/high-risk disease. Non–nerve-sparing procedures were more frequently performed in the elderly group and operative time, blood loss, hospital stay and complication rates were similar between the two groups. The rate of early urinary continence recovery was lower among older patients, but by 12 months continence rates were nearly identical. Elderly patients showed more advanced pathological tumor stages, more PSA persistence and a higher need for adjuvant hormonal therapy, while rates of positive surgical margins and biochemical recurrence were comparable. RS-RARP can be safely offered to selected patients aged ≥ 75 years without compromising perioperative safety or oncological control. Despite delayed continence recovery, one-year functional outcomes are equivalent, supporting RS-RARP as a viable treatment option for appropriately chosen elderly men with localized prostate cancer.

AIM:To evaluate real-world local control outcomes and identify clinical and dosimetric determinants of local progression following metastasis-directed stereotactic ablative radiotherapy (SABR) within the international OligoCare cohort. METHODS:OligoCare is a prospective observational registry (EORTC-ESTRO E2-RADIatE) evaluating SABR for oligometastatic prostate, breast, colorectal, and non-small cell lung cancer (NSCLC). The secondary endpoint, local progression, was defined as recurrence within the planning target volume (PTV), with death treated as a competing risk. Multivariate analyses were performed at both the patient and lesions levels (restricted to single-lesion patients) to account for confounding factors. RESULTS:Between July 2019 and July 2025, 2,805 eligible patients were enrolled. Of these, 2,447 from 57 institutions received the recommended protocol treatment and were included in the analysis (median follow-up 31 months). The distribution of primary tumors was prostate (41.7%), NSCLC (21.7%), colorectal (21.2%), and breast (15.4%). The 1- and 3-year local progression rates were 5.0% and 11.4%, respectively. Among single-lesion patients (n = 1,714), a higher PTV minimum dose was the sole independent predictor of local control, with an 11% risk reduction per 10 Gy EQD2 increase (HR 0.89 [97.5% CI 0.82-0.98], p = 0.005). Although de novo OMD showed better local control compared to repeat OMD in the patient-level analysis (HR0.65 [97.5% CI 0.47-0.91], p = 0.004), this effect was largely driven by higher dose delivery in de novo cases. Colorectal primaries faced a significantly higher risk of progression than prostate cancer (HR 2.63 [97.5% CI 1.71-4.05], p < 0.001), despite receiving the highest dose per fraction. CONCLUSION:SABR provides durable real-world local control in oligometastatic disease. Optimizing the minimum PTV dose appears the most critical technical factor for success. The inferior local control observed in colorectal metastases suggests a combination of treatment intensity challenges and intrinsic radioresistance, which could guide future trial design and dose-escalation strategies.

BACKGROUND:Various locoregional treatments exist for PET-CT-detected pelvic nodal oligorecurrences in patients with prostate cancer. We aimed to assess whether elective nodal radiotherapy (ENRT) to the pelvis would be superior to metastasis-directed therapy (MDT). METHODS:PEACE V-STORM is a phase 2, open-label, randomised, controlled trial conducted in 21 hospitals in Australia, Belgium, Italy, Norway, Spain, and Switzerland. Eligible participants were aged 18 years or older, with WHO performance status 0-1 and a histologically confirmed initial diagnosis of adenocarcinoma of the prostate, with a PET-detected pelvic nodal oligorecurrence (up to five nodes) following radical local treatment. Patients were randomly assigned (1:1) to MDT or ENRT. Randomisation was done online by minimisation with randomisation factor 0·80 and was stratified by type of PET tracer (choline vs prostate-specific membrane antigen) and type of MDT used (salvage lymph node dissection vs stereotactic body radiotherapy or simultaneous integrated boost). Participants and researchers were not masked to treatment assignment. Patients in the MDT group had salvage lymph node dissection or stereotactic body radiotherapy (30 Gy in three fractions every other day), with 6 months of androgen deprivation therapy. Patients in the ENRT group received a 45 Gy dose in 25 fractions to the pelvis with a simultaneous integrated boost of 65 Gy to the PET-positive nodes or salvage lymph node dissection, with 6 months of androgen deprivation therapy. The primary endpoint was metastasis-free survival, defined as the time between randomisation and the appearance of a metastatic recurrence (any M1) on PET imaging or death due to any cause, and was analysed per modified intention to treat. This study is registered with ClinicalTrials.gov, NCT03569241, and the Swiss National Clinical Trials Portal, SNCTP000002947, and is active, not recruiting. FINDINGS:Between June 11, 2018, and April 30, 2021, 198 patients were screened for eligibility, 196 of whom were randomly assigned to MDT (n=99) or ENRT (n=97), with 190 evaluable patients (MDT n=97 and ENRT n=93). All patients were male. Data on race and ethnicity were not collected. Median follow-up was 50 months (IQR 42-58). 4-year metastasis-free survival was 63% (80% CI 56-69) in the MDT group and 76% (69-81) in the ENRT group (HR 0·62 [80% CI 0·44-0·86]; p=0·063). The most common grade 3 adverse events were urinary incontinence (six [6%] of 97 in the MDT group vs nine [10%] in the ENRT group) and diarrhoea (one [1%] in the MDT group vs two [2%] in the ENRT group). No treatment-related deaths occurred. INTERPRETATION:To our knowledge, this is the first randomised trial for metachronous PET-detected nodal recurrences comparing two local treatment approaches (MDT and ENRT) in combination with 6 months of androgen deprivation therapy. By showing an improved metastasis-free survival with ENRT, this trial establishes ENRT as a potential standard treatment approach, awaiting a phase 3 trial confirming these results. FUNDING:Movember Foundation, Kom Op Tegen Kanker, Stichting tegen Kanker.

BACKGROUND AND OBJECTIVE:External beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) is standard for high-risk prostate cancer. EORTC 1414 compared ADT with a luteinizing hormone-releasing hormone (LHRH) antagonist (degarelix) or an LHRH agonist in patients who received EBRT. METHODS:Between 2017 and 2023, 379 patients with prostate cancer with at least two high-risk features (prostate-specific antigen [PSA] ≥20 ng/ml, Gleason score ≥8, cN1, or cT3-4) and stage M0 on conventional imaging or stage M1a/b (n = ≤3 lesions) on advanced imaging were enrolled. Patients were randomized to receive 18, 24, or 36 mo of ADT (degarelix, n = 190; LHRH agonist, n = 189) with pelvic EBRT and treatment of all metastases. Owing to low accrual, the primary endpoint was changed from progression-free survival (PFS) to the PSA nadir response (<0.1 vs ≥0.1 ng/ml) within 6 mo after EBRT. KEY FINDINGS AND LIMITATIONS:Median age was 72 yr. A PSA nadir of <0.1 ng/ml was achieved by 60% of patients in the agonist arm and 52% in the degarelix arm (odds ratio 0.73, 95% confidence interval 0.43-1.22; p = 0.9). Two-year PFS was 88% in both arms. Adverse events occurred in 89% of agonist and 88% of degarelix patients. Among 41 patients with baseline cardiovascular (CV) disease, four in the agonist arm and one in the degarelix group experienced a CV event. Two CV-related deaths occurred in the agonist arm. Degarelix improved lower urinary tract symptoms, particularly in patients with a baseline International Prostate Symptom Score of ≥13. Limitations include early closure and insufficient power to assess PFS. CONCLUSIONS AND CLINICAL IMPLICATIONS:Degarelix did not improve the PSA nadir response within 6 mo after EBRT in comparison to LHRH agonists, but was associated with lower incidence of CV events among patients with pre-existing CV disease.

External beam radiotherapy (EBRT) is a standard treatment for localized prostate cancer, with recent advancements favoring a reduced number of treatment sessions. Stereotactic body radiotherapy (SBRT) is a form of radiotherapy that delivers higher doses per fraction, typically in five or fewer sessions. This retrospective study aims to evaluate the implementation of the PACE-SBRT protocol for localized prostate cancer at our center by assessing the incidence and severity of toxicity, as well as biochemical relapse-free survival. We conducted a retrospective analysis of patients with localized prostate cancer treated with SBRT at the Iridium Network in Antwerp, Belgium, who were treated between January 1, 2020, and December 31, 2022. Data were extracted from electronic medical records and included descriptive information on patient outcomes. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Acute toxicity was defined as events occurring within 90 days post-SBRT, whereas late toxicity was evaluated at 6 months, 1 year, 2 years, and 3 years post treatment. Biochemical recurrence was defined via the Phoenix criteria, as a rise in PSA levels of 2 ng/mL or more above the post treatment nadir. A total of 267 patients met the eligibility criteria for this study. In total, 9

BACKGROUND AND OBJECTIVE:Patients with muscle-invasive bladder cancer (MIBC) who develop a recurrence after radical cystectomy (RC) have poor outcomes. This study aims to evaluate the safety and efficacy of adjuvant radiotherapy (ART) in mitigating pelvic recurrences in high-risk MIBC patients. We report on survival outcomes, health-related quality of life (HRQoL), and hematological toxicity for these patients. METHODS:A multicentric phase 2 trial was conducted from August 2014 to October 2020, in which 72 high-risk MIBC patients received ART after RC. High risk was defined by the presence of one or more of the following criteria: pT3 stage and lymphovascular invasion, pT4 stage, fewer than ten lymph nodes removed, positive lymph nodes, and positive surgical margins. Using intensity-modulated radiotherapy, patients with pelvic lymph nodes ± cystectomy bed (in case of a positive surgical margin) received 50 Gy in 25 fractions. Outcomes were local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS) (Kaplan-Meier statistics), HRQoL (European Organisation for Research and Treatment of Cancer QLQ-C30/QLQ-BLM30 surveys), and hematological toxicity (Common Terminology Criteria for Adverse Events grading). KEY FINDINGS AND LIMITATIONS:The median follow-up of patients without a recurrence was 39 mo. At 2 and 5 yr, LRFRs were 81% (95% confidence interval [CI] 71-91%) and 79% (95% CI 68-89%), CRFS rates were 32% (95% CI 21-42%) and 20% (95% CI 11-30%), and OS rates were 48% (95% CI 36-59%) and 34% (95% CI 22-45%), respectively. At the end of ART, several symptoms worsened, most returning to baseline within the first few months. Diarrhea showed the greatest deterioration, recovering to baseline score only partially. Hematological toxicity of incidence grade ≥2 included lymphopenia (75%), neutropenia (2%), thrombopenia (2%), and anemia (17%). Limitations include the single-arm design and the limited availability of blood samples and surveys. CONCLUSIONS AND CLINICAL IMPLICATIONS:ART after RC is well tolerated and leads to a favorable local control rate, supporting its use in clinical practice.

BACKGROUND AND PURPOSE:Computed tomography (CT) imaging poses challenges for delineation of soft tissue structures for prostate cancer external beam radiotherapy. Guidelines require the input of magnetic resonance imaging (MRI) information. We developed a deep learning (DL) prostate and organ-at-risk contouring model designed to find the MRI-truth in CT imaging. MATERIAL AND METHODS:The study utilized CT-scan data from 165 prostate cancer patients, with 136 scans for training and 29 for testing. The research focused on contouring five regions of interest (ROIs): clinical target volume of the prostate including the venous plexus (VP) (CTV-iVP) and excluding the VP (CTV-eVP), bladder, anorectum and the whole seminal vesicles (SV) according to The European Society for Radiotherapy and Oncology (ESTRO) and Advisory Committee on Radiation Oncology Practice (ACROP) contouring guidelines. Human delineation included fusion of MRI-imaging with the planning CT-scans in the process, but the model itself has never been shown MRI-images during its development. Model training involved a three-dimensional U-Net architecture. A qualitative review was independently performed by two clinicians scoring the model on time-based criteria and the DL segmentation results were compared to manual adaptations using the Dice similarity coefficient (DSC) and the 95th percentile Hausdorff distance (HD95). RESULTS:The qualitative review of DL segmentations for CTV-iVP and CTV-eVP showed 2 or 3 out of 3 in 96 % of cases, indicating minimal manual adjustments were needed by clinicians. The DL model demonstrated comparable quantitative performance in delineating CTV-iVP and CTV-eVP with a DSC of 89 % with a standard deviation of 3.3 %. HD95 is 4 mm for CTV-iVP and 4.1 mm CTV-eVP with a standard deviation of 2.1 mm for both contours. Anorectum, bladder and SV scored 3 out of 3 in the qualitative analysis in 62 %, 72 % and 55 % of cases respectively. DSC and HD95 are 90 % and 5.5 mm for anorectum, 96 % and 2.9 mm for bladder, and 81 % and 4.6 mm for the seminal vesicles. CONCLUSION:To our knowledge, this is the first DL model designed to implement MRI contouring guidelines in CT imaging and the first model trained according to ESTRO-ACROP contouring guidelines. This CT-based DL model presents a valuable tool for aiding prostate delineation without requiring the actual MRI information.

BACKGROUND AND OBJECTIVE:In high-risk prostate cancer, the proPSMA trial showed upstaging with prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in 14% of patients. We hypothesised that the probability of stage migration in a patient population referred for curative-intent radiotherapy would be higher. Here we report stage migration results according to PSMA PET/CT in the first year of inclusion in the phase 2/3 THUNDER trial (NCT06282588). METHODS:Patients with high-risk prostate cancer screened between December 2023 and December 2024 in the THUNDER trial with both conventional imaging (CT, bone scintigraphy) and PSMA PET/CT within 16 weeks before screening were included (n = 142). Stage migration according to the TNM classification versus the molecular imaging (miTNM) classification (PROMISE v2 criteria) was assessed using descriptive statistics. KEY FINDINGS AND LIMITATIONS:PSMA PET/CT led to stage migration in 43 patients, of whom 42 (30%) were upstaged and one (1%) was downstaged. Upstaging to miN1-2 disease occurred in 32 patients (23%), and to miM1a-c disease in 19 patients (13%). The probability of upstaging increased with the number of high-risk features. In the subgroup meeting the STAMPEDE M0 high-risk criteria (n = 73), PSMA PET/CT upstaged 27 patients (37%), including upstaging to miM1a-c disease in 14 (19%). Limitations include the absence of central review of the imaging procedures. CONCLUSIONS AND CLINICAL IMPLICATIONS:One-third of patients with high-risk prostate cancer referred for curative-intent radiotherapy were upstaged on PSMA PET/CT. This finding supports the use of PSMA PET/CT for staging, especially in patients with multiple high-risk features, and suggests a need for treatment adaptations accordingly, which will be further investigated in the THUNDER trial.