BACKGROUND:For over a decade the Advanced Prostate Cancer Consensus Conference (APCCC) covers a variety of topics that greatly impact daily practice. In 2025, a dedicated event was organised to discuss key questions in clinical management of patients with prostate cancer (PC) related to diagnostic tools (APCCC Diagnostics). Here we present the voting results of the APCCC Diagnostics questions. OBJECTIVE; DESIGN, SETTING, AND PARTECIPANTS: APCCC Diagnostics 2025 is a pilot project. The scientific committee for APCCC Diagnostics 2025 developed 88 multiple-choice consensus questions on six different topics. Prior to the conference, the panel members (''panellists'') voted on these questions via a web-based survey. Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS:Consensus was only reached on 17 of 88 questions (19%), of which six (7%) received a strong consensus. Specifically, consensus was reached for two of 17 questions (14%) in "how to diagnose PC"; seven of 16 (44%) in "how to stage PC"; three of 14 (21%) in "Biochemical Recurrence Scenario"; two of 11 (18%) in "metastatic disease: what to do?"; zero of 18 (0%) in "monitoring metastatic PC"; and three of 12 (25%) in "radioligand therapy and imaging." CONCLUSIONS:The voting results and their discussion may assist physicians in navigating controversial areas of clinical management related to diagnosis, staging, and restaging in the different clinical settings for PC, particularly where high-level evidence is scarce or conflicting. The findings can also help funders and policymakers in prioritising areas for future research.

PURPOSE:To evaluate the feasibility and dosimetric safety of prostate stereotactic radiotherapy (SBRT) with an empty bladder approach. METHODS:Eligible patients had histologically confirmed prostate cancer and planned for SBRT (35-36.25 Gy/5# to prostate ± 25 Gy to pelvic nodes, alternate days or once-weekly). Participants voided immediately before planning CT scan and each SBRT fraction. Interfraction bladder volume variability was evaluated with on-board cone beam CT. Primary endpoint was the rate of acute urinary grade 2+ AE (CTCAE v5.0), with a non-inferiority margin of +10% compared to a 32% reference rate from the XXX randomized trial (NCTXXXXXX) using similar planning constraints. RESULTS:Simulation scan was acquired with an empty bladder for 139 patients, of which planning constraints were achieved for 118 patients (simulation bladder volume ≤10cc deemed unsuitable for empty bladder workflow, n=7; planning constraints not met, n=14). These 118 patients were treated with empty bladder and constituted the trial cohort evaluable for safety. Median simulation empty bladder volume was 77 cc (IQR 59 - 110). Interfraction bladder volume variation for individual patients was 18%. Grade ≥2 urinary AE occurred in 28.1% (90% CI 21.2-35.8), meeting the non-inferiority threshold. Grade 3 AE were rare (urinary n=1, 0.9%; GI = 0), and 7.9% had grade 2 GI AE. Higher bladder volume at simulation was associated with a higher risk of gr2+ urinary AE [Odds ratio 1.02 (95% CI 1.01 - 1.03), p = 0.002]. Once-weekly SBRT was associated with lower GI AE (0% vs 12.9%, p = 0.03) but not urinary AE. CONCLUSION:Prostate SBRT delivered with an empty bladder was observed to be dosimetrically feasible, reproducible, with acute safety comparable to standard full bladder protocols. If validated in larger studies, it may offer a time-efficient and patient-friendly alternative in routine prostate SBRT practice.

AIM:Assessment of maximum standardized uptake value (SUVmax) values and patterns of uptake on 68Ga prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) in benign and malignant prostatic lesions. METHODS:Retrospective observational study of prostate cancer patients referred for 68Ga-PSMA PET/CT for initial staging. SUVmax of the prostatic lesion was correlated with risk category, International Society of Urological Pathology (ISUP) grade groups, prostate-specific antigen (PSA), and Gleason score. Uptake patterns across risk categories were also evaluated. RESULTS:A total of 325 subjects were included (14 benign and 311 malignant). Median SUVmax of benign lesions was 8.29. Grade groups 4 and 5 showed significantly higher median SUVmax values (26.42 and 26.55) than other grade groups. SUVmax correlated positively with ISUP grade group, Gleason score, and serum PSA (all P < 0.001). SUVmax differed significantly among benign/low-, intermediate-, and high-risk groups. Receiver operating characteristic analysis identified an SUVmax cut-off of 10.91 for diagnosing prostate cancer, with 80% sensitivity, 79% specificity, 98.8% positive predictive value, and 80% diagnostic accuracy. Uptake pattern within the prostate did not differ significantly across risk categories. CONCLUSION:SUVmax differentiates high-risk from low- and intermediate-risk prostate cancer and may serve as a noninvasive independent prognostic marker. Intraprostatic uptake pattern has no significant role in lesion categorization.

PURPOSE:Intermediate-risk and poor-risk nonseminomatous germ cell tumors (NSGCTs) have inferior survival outcomes compared with earlier stages. This study reports the survival outcomes and proposes a prognostic reclassification to identify the poorest risk subset within these groups. METHODS:A retrospective analysis was conducted on consecutive patients 15 years and older with intermediate-risk or poor-risk NSGCTs, as per the International Germ Cell Cancer Collaborative Group classification, treated at a tertiary cancer center in western India from 2015 to 2021. Survival outcomes were analyzed using the Kaplan-Meier method, with multivariate analyses identifying prognostic factors. A risk factor model and nomogram were developed and compared with the existing classification. RESULTS:A total of 400 patients were included with a median follow-up of 60.2 months; 5-year overall survival (OS) was 84.6% for intermediate-risk and 52.6% for poor-risk patients (P < .001). Five-year relapse-free survival (RFS) was 77.0% and 45.6%, respectively (P < .001). Age 35 years and older; mediastinal primary; and liver, lung, and brain metastases were significant factors for both RFS and OS by multivariate analyses. Additionally, lactate dehydrogenase >10× upper limit of normal was significant for RFS while alpha-fetoprotein >10,000 ng/mL was significant for OS. The risk factor model stratified patients (0, 1, 2, ≥3 factors) with 5-year OS of 90.3%, 69.6%, 53.8%, and 27.1%, respectively, outperforming existing classification (c-index: 0.668 v 0.629 for OS; 0.666 v 0.619 for RFS). A validated nomogram further enhanced prognostic precision. CONCLUSION:This largest single-center Indian cohort of intermediate-risk and poor-risk NSGCTs identifies a "poorest risk" subset who may benefit from treatment intensification and novel strategies.

e17032 Background: The optimal neoadjuvant chemotherapy (NACT) regimen for high-risk penile carcinoma (bulky, bilateral or pelvic nodes) is unclear. Although paclitaxel, ifosfamide and cisplatin (TIP) is used based on limited prospective data, platinum doublets are commonly used in real-world practice due to feasibility and toxicity concerns. Methods: We retrospectively analyzed patients with high-risk penile squamous carcinoma (clinical N2-N3) treated with NACT at Tata Memorial Centre between January 2016 and June 2025, comparing TIP with platinum doublet. Results: Among 58 patients (median age - 55 years), 31% were tobacco chewers, 15.5% were smokers, 22.4% were hypertensive and 13.8% were diabetic (Table 1). NACT regimens included paclitaxel carboplatin (60.3%), TIP (36.2%) and cisplatin 5-FU (3.4%). On histology, 8.6% were p16 positive and 37.9% were poorly differentiated. At a median follow-up of 10.5 months, TIP showed numerically longer DFS (8.9 vs 5.8 months, p = 0.55) and OS (12.6 vs 10.3 months, p = 0.564). Lung metastases occurred in 29.3%. Metronomic chemotherapy was offered to 22.4%; 41.4% were offered best supportive care. TIP had more grade 3/4 hematological toxicities (19% vs 8.1%) and hospitalizations (9.5% vs 8.1%), whereas platinum doublet had more gastro-intestinal toxicities (10.8% vs 0) and electrolyte disturbances (13.5% vs 4.8%), with rare serious events (encephalopathy, pneumonia and stroke) in both groups. Conclusions: In this real-world cohort, TIP showed numerically longer DFS and OS but higher hematologic toxicity, while platinum doublets were more feasible and better tolerated, underscoring the need for prospective studies in this rare disease. Characteristics TIP(n = 21) Platinum Doublet(n=37) p-value Age > 60 years 7 (33.3%) 14 (37.8%) 0.732 ECOG PS 0.863 0 9 (42.9%) 15 (40.5%) 1 12 (57.1%) 22 (59.5%) Clinical N stage 0.234 N2 4 (19%) 3 (8.3%) N3 17 (81%) 33 (91.7%) Completed > 3 cycles NACT 16 (76.2%) 29 (78.4%) 0.848 Response to NACT 0.273 Complete response 0 1 (2.7%) Partial response 12 (57.1%) 12 (32.4%) Stable disease 5 (23.8%) 11 (29.7%) Progressive disease 4 (19%) 13 (35.1%) Primary Surgery 0.487 Wide local excision 2 (9.5%) 4 (10.8%) Partial penectomy 13 (61.9%) 18 (48.6%) Total penectomy 5 (23.8%) 8 (21.6%) Not done 1 (4.8%) 7 (18.9%) Inguinal node dissection 0.049 Unilateral 0 1 (2.7%) Bilateral 18 (85.7%) 20 (54.1%) Pelvic node dissection 0.010 Unilateral 2 (9.5%) 3 (8.1%) Bilateral 15 (71.4%) 12 (32.4%) Pathological T stage 0.127 T1 5 (23.8%) 3 (8.1%) T2 7 (33.3%) 8 (21.6%) T3 5 (23.8%) 9 (24.3%) Pathological N stage 0.044 N0 2 (9.5%) 6 (16.2%) N1 1 (4.8%) 0 N3 15 (71.4%) 15 (40.5%) Extra-nodal extension 14 (66.7%) 14 (37.8%) 0.070 Adjuvant therapy 0.341 Radiation 2 (9.5%) 2 (5.4%) Chemoradiation 7 (33.3%) 7 (18.9%) Site of progression 0.947 Loco-regional 8 (38.1%) 15 (40.5%) Metastatic 10 (47.6%) 16 (43.2%)

Background:Prostate cancer is an emerging public health concern in India, with rising incidence and varying survival outcomes. This study aimed to evaluate 5-year overall survival and identify prognostic factors among prostate cancer patients treated at Tata Memorial Hospital (TMH), Mumbai. Methods:This retrospective study included all patients newly diagnosed with prostate cancer between January and December 2017 who received cancer-directed treatment at TMH. Patients were followed through 2022. Clinico-epidemiological variables including age, PSA levels, Gleason grade, clinical extent (EAU risk group classification), intent, completion status and treatment modality were analysed. Kaplan-Meier survival curves and Cox proportional hazards models were used to assess survival outcomes. Results:A total of 421 patients were included, with a mean (SD) age of 66 ± (8.39) years and a median (IQR) PSA of 45.9 (17-154) ng/ml. All patients were symptomatic at presentation, predominantly with urinary complaints (90.5%), followed by bone pain (3.6%) or both (5.9%). At diagnosis, 15.2% had localized disease, 25.8% had locally advanced disease, and 58.4% had metastatic cancer. The overall 5-year survival rate was 61%. Prognostic factors significantly associated with survival included age, PSA, Gleason grade and disease extent. Patients with PSA > 1000 ng/ml had the poorest prognosis (33% 5-year survival). Survival varied by age group, declining from 66% in those aged 66-75 years to 45% in patients >75 years, although this trend was not statistically significant in adjusted analysis (p = 0.46). Disease extent demonstrated a strong survival gradient: 89% in localized disease, 79% in locally advanced and 41% in metastatic cancer, with metastatic disease showing a significantly increased adjusted mortality risk (HR: 4.59; p 0.004). Curative treatment intent was associated with markedly better outcomes, with a 5-year survival of 81% compared to 40% among those receiving palliative care. Similarly, treatment adherence had a substantial impact on prognosis, with patients completing therapy achieving a 65% 5-year survival rate, in contrast to only 12% among those with incomplete treatment (adjusted HR: 3.62; p < 0.001). Treatment modality also influenced survival: patients treated with ADT alone had the lowest 5-year survival (35%) and a significantly higher mortality risk (adjusted HR:1.65; p 0.01), whereas outcomes were more favourable with radical prostatectomy with adjuvant therapy (75%; adjusted HR: 1.21 p 0.80). Conclusion:Survival in prostate cancer is strongly influenced by clinical extent at diagnosis, PSA, Gleason grade and treatment. Improving early detection, expanding multimodal treatment strategies and ensuring treatment completion are critical to enhancing outcomes in India.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy arising from the adrenal cortex, characterized by local invasion and frequent distant metastases. Tumor size is a key predictor of malignancy, with lesions larger than 4 cm carrying a high likelihood of being malignant. Subsets of ACCs are functional, secreting excess glucocorticoids, sex steroids, or mineralocorticoids, leading to characteristic clinical syndromes. Diagnosis is often delayed due to nonspecific presentations, and management remains challenging because of limited effective systemic therapies, high recurrence rates, and the rarity of the disease, which restricts large-scale clinical trials. This review provides an overview of the current strategies in the diagnosis, staging, and treatment of ACC, and discusses the evolving therapeutic modalities. A narrative literature review was conducted using relevant publications from PubMed, Scopus, and recent international guidelines. Data from key trials and consensus statements were incorporated. Complete surgical resection, which entails adrenalectomy with local lymph node dissection, is the mainstay of curative treatment. Adjuvant mitotane and radiation therapy are currently the cornerstone of treatment post-surgery in those with high-risk features. High-risk tumors are those with incomplete resection, high grade, and Ki67>10%. Studies are ongoing to determine the role of chemotherapy in the adjuvant setting. The etoposide-doxorubicin-cisplatin (EDP) regimen, combined with mitotane, is the current standard of care for advanced disease. New therapies targeting tumor genomics or the immune microenvironment are under investigation. Adrenocortical carcinoma management requires a multidisciplinary and individualized approach. Further research into molecular and immunotherapeutic strategies is needed to improve patient outcomes.

BACKGROUND AND OBJECTIVE:BRCA1 and BRCA2 pathogenic germline variants (PGVs) are associated with higher risk of prostate cancer (PC). The IMPACT study evaluated the utility of targeted prostate-specific antigen (PSA) screening in BRCA1/BRCA2 PGV carriers. Here we report outcomes after five rounds of PSA screening in IMPACT. METHODS:Between 2005 and 2015, 3063 participants aged 40-69 yr (median 54 yr) were recruited from 65 centres in 20 countries in two cohorts: (1) BRCA1/BRCA2 PGV carriers (915 BRCA1, 901 BRCA2); and (2) age-matched noncarriers for a familial PGV (727 BRCA1 and 520 BRCA2 noncarriers). Annual PSA screening was performed, with PSA >3.0 ng/ml used as the indication for prostate biopsy. Our aim was to identify differences by PGV status in (1) the incidence of PC and of clinically significant PC (csPC; grade group ≥2) and (2) tumour stage and characteristics after five screening rounds. KEY FINDINGS AND LIMITATIONS:There was no statistically significant difference in PC incidence between BRCA1/BRCA2 PGV carriers and noncarriers. csPC incidence was significantly higher for BRCA2 PGV carriers than for noncarriers (3.1% vs 1.3%; p = 0.04). Among men with PC, the proportion of tumours with National Comprehensive Cancer Network intermediate unfavourable/high risk was higher in the BRCA1/BRCA2 PGV groups versus the corresponding group without PGVs (BRCA2: 65% vs 32%, p = 0.029; BRCA1: 56% vs 18%, p = 0.0017). There were no T4 or metastatic PC cases. Pathology after radical prostatectomy revealed tumour upgrading for 7/23 (26%) BRCA1 PGV carriers and 10/34 (26%) BRCA2 PGV carriers, with no tumour upgrading for men without PGVs. Study limitations include the biopsy compliance rate and changes in PC diagnostic pathways since 2005. CONCLUSIONS AND CLINICAL IMPLICATIONS:Annual PSA screening in BRCA2 PGV carriers confirmed a higher incidence of csPC and detection of clinically relevant tumours in comparison to noncarriers. For the first time, we confirm that PSA screening in BRCA1 PGV carriers results in early detection of NCCN IR-U/HR PC. Systematic PSA screening is recommended for BRCA2 PGV carriers and should be considered for BRCA1 PGV carriers.

Purpose Prostate stereotactic ablative body radiotherapy (SABR) is now a standard-of-care radiation therapy option for prostate cancer based on high-level clinical trial evidence. As part of the Australia and New Zealand (ANZ) prostate SABR guideline development process, the Royal Australian and New Zealand College of Radiologists has commissioned a pattern-of-practice survey on contemporaneous prostate SABR practice. Methods and Materials We conducted a cross-sectional survey among ANZ genitourinary radiation oncologists (ROs), focusing on patient selection, contouring, treatment planning, and delivery of prostate SABR. Results A total of 53 ROs across ANZ responded to the survey (response rate: 28%). Of the 41 ROs currently offering prostate SABR, 95%, 90%, 35%, 5%, and 0% offer prostate SABR as standard-of-care options to individuals with favorable intermediate risk, unfavorable intermediate risk, favorable high risk (NINJA/ TROG18.01 trial eligible), very high risk, and node-positive prostate cancer, respectively. Most ROs (86%) routinely use fiducial markers. All ROs routinely request planning magnetic resonance imaging for contouring. Clinical target volume contouring ranged from prostate alone (26%) to prostate plus proximal 1 cm of the seminal vesicles (81%). Planning target volume margins ranged from 3 to 5 mm. An anisotropic 5 mm margin with 3 mm posteriorly was most common (56%). Nineteen (45%) ROs provide a focal boost to the intraprostatic lesion. The most common dose fractionation was 36.25 Gy to the planning target volume and 40 Gy to the clinical target volume over 5 fractions, delivered as 2 (50%) to 3 fractions (76%) per week. The majority of ROs offer prostate SABR on standard computed tomography-linear accelerator (LINAC) (88%), with several ROs also treating patients with CyberKnife (10%) and magnetic resonance-LINAC (5%). Of the ROs who use standard computed tomography-LINAC, 84% use intrafraction motion monitoring. Twelve (23%) ROs do not offer prostate SABR. The main barrier cited was a lack of expertise (42%). Conclusions This ANZ-wide prostate SABR pattern-of-practice survey demonstrated some variations in practice, providing contemporary insight into how prostate SABR is delivered across ANZ and highlighting barriers to wider adoption.

BACKGROUND AND OBJECTIVE:Most patients with high-risk localized prostate cancer (HRLPC) do not undergo stereotactic body radiotherapy (SBRT) in part because of the limited evidence of long-term outcomes. We report long-term efficacy and toxicity outcomes for men treated with SBRT for HRLPC. METHODS:Individual patient data from ten prospective clinical studies evaluating SBRT for HRLPC across nine institutions were pooled in the Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate consortium. The Kaplan-Meier method was used to estimate 5-yr biochemical recurrence (BCR) and distant metastasis (DM), stratified by receipt of intensified treatment (≥12 mo of androgen deprivation therapy [ADT] with extremely dose-escalated [≥8 Gy/fraction] prostate-directed SBRT). The impact of intensified treatment on BCR-free survival and DM-free survival was evaluated using multivariable Cox proportional hazards models. Late Common Terminology Criteria for Adverse Events grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity was analyzed using time-to-event models. KEY FINDINGS AND LIMITATIONS:In 440 patients with a median follow-up time of 60.4 mo, 5-yr BCR and DM rates were 22% (95% confidence interval [CI] = 17-26%] and 9.2% (95% CI = 6.2-12%), respectively. In the 93 patients (21%) who received intensified treatment, 5-yr BCR and DM rates were 7.4% (95% CI = 1.7-13%) and 3.7% (95% CI = 0-7.9%), respectively. Receipt of intensified therapy was associated with a significant reduction in both BCR (hazard ratio [HR] = 0.38 [95% CI = 0.20-0.74], p = 0.005) and DM (HR = 0.43 [95% CI = 0.18-0.99], p = 0.049). For the overall cohort, 5-yr rates of grade ≥2 GU and GI toxicity were 23% (95% CI = 19-27%) and 10% (95% CI = 7-13%), respectively. Limitations include heterogeneous treatment techniques and the nonrandomized nature of the study. CONCLUSIONS AND CLINICAL IMPLICATIONS:The safety and efficacy profile of SBRT for HRLPC remains favorable at long-term follow-up, and SBRT should be integrated into shared decision-making for treatment of HRLPC.

Oligometastatic prostate cancer represents a distinct biological state between localized and widely metastatic disease, characterized by a limited number of lesions. Stereotactic body radiotherapy (SBRT) has emerged as a key metastasis-directed therapy (MDT), enabling precise ablation of metastatic lesions with minimal toxicity. Prospective clinical trials such as SABR-COMET, STOMP, ORIOLE, RADIOSA, and EXTEND have shown that SBRT delays disease progression, prolongs progression-free survival, and postpones the need for systemic therapy, while maintaining a favorable safety profile. Nevertheless, methodological limitations persist, including heterogeneity in defining oligometastatic disease, variability in dosing and fractionation, and the lack of predictive biomarkers. Ongoing phase III trials aim to validate the integration of SBRT with modern systemic therapies, including next-generation androgen receptor pathway inhibitors, to optimize clinical outcomes in hormone-sensitive and castration-resistant oligometastatic prostate cancer. This review summarizes current evidence, clinical applications, and future directions for SBRT in this patient population.

ABSTRACT Objectives HPV‐negative oropharyngeal squamous cell cancer (OPSCC) is associated with poor clinical outcomes. The main objective of this study was to evaluate prognostic factors of OPSCC treated with definitive chemoradiotherapy (CTRT). Materials and Methods Consecutive patients of OPSCC treated with definitive CTRT in a tertiary care center from January 2013 to December 2017 were analysed retrospectively. Kaplan–Meier method was used for survival analysis, Log‐rank test was used for univariate analysis (UVA), and Cox regression method was used for multivariate analysis (MVA). Results Out of 630 eligible patients, 543 (86.1%) had locally advanced stage according to AJCC 7th edition. HPV status was known for 500 patients, of which 55 (11%) tested p16 positive, reflecting a predominantly HPV‐negative cohort. Chemo‐radiotherapy was offered to 447 (71%) patients. Intensity‐modulated‐radiotherapy (IMRT) technique was used for 163 (25.9%) patients. On UVA KPS ≤ 80 (p = 0.001), p16 negative tumours (p < 0.001), T3‐T4 stage (p < 0.001), advanced group stage (AJCC 8th ed.) (p < 0.001), conventional RT technique (p < 0.001), RT dose < 66 Gy EQD2 (p < 0.001) and residual disease after treatment (p < 0.001) were associated with poor Locoregional control (LRC) rates. On MVA p16 negative tumours (HR 3.1 [95% CI 1.8–5.3]), T3‐T4 stage (HR 1.6 [95% CI 1.2–2.2]), conventional RT technique (HR 1.6 [95% CI 1.5–2.3]), RT dose < 66 Gy EQD2 (HR 2.2 [95% CI 1.5–3.4]) were independent prognostic factors for poor LRC. These variables were also significant for local control, disease‐free free and overall survival. Conclusion In this predominantly HPV‐negative OPSCC cohort, HPV status, T stage, RT technique, and RT doses > 66 Gy were independent prognostic factors for all outcomes.

PURPOSE:To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC). METHODS:Patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, ≤10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence-free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS). RESULTS:From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively. CONCLUSION:Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.

PURPOSE:Advances in imaging have enabled identification of intraprostatic GTVs, creating opportunities for micro-boosting in prostate radiotherapy. However, variability exists in patient selection, target delineation, and treatment planning. This study aimed to characterize expert contouring variability and establish consensus guidance for GTV micro-boosting using a contour-based modified Delphi consensus. METHODS:International radiation oncologists with expertise in GTV micro-boosting participated in a two-part study comprising a contouring exercise and a two-round modified Delphi consensus. Participants contoured GTVs on two prostate cancer cases with mpMRI and PSMA-PET imaging, including one complex case with imaging discordance. Contouring agreement was assessed using Fleiss' kappa, intraclass correlation coefficients (ICC), and STAPLE analysis. Subsequently, participants completed iterative Delphi surveys addressing patient selection, imaging requirements, contouring practices, and treatment planning. Consensus and strong consensus were predefined as ≥75% and ≥90% agreement, respectively. RESULTS:Fifteen of 20 invited experts completed the study. Contouring agreement was high in the simpler case but substantially lower in the complex case. PSMA-PET-based GTVs were consistently larger than mpMRI-based GTVs. Overall, consensus or strong consensus was achieved for 43 of 131 statements (33%). Agreement was reached on key aspects of GTV delineation, including use of combined T2 and DWI/ADC sequences on mpMRI, eligibility of PI-RADS 4-5 and PROMISE 4-5 lesions for boosting, preferred use of PSMA-targeted tracers, and avoidance of CTV margins when PET and MRI information are used in combination. No consensus was achieved on SBRT micro-boosting outside clinical trials, margin expansion using single-modality imaging, or optimal dose prescriptions to the GTV or uninvolved prostate. CONCLUSION:This contour-based modified Delphi study demonstrates variability in GTVs delineation for complex cases and identifies areas of expert consensus that can inform standardized implementation of prostate GTVs micro-boosting.

6082 Background: Locally advanced thyroid cancers have high rates of locoregional recurrence after standard treatment with surgery and radioactive iodine (RAI). Repeated surgery and RAI in recurrent disease contributes to significant morbidity. Retrospective studies have shown that the addition of adjuvant external beam radiotherapy (EBRT) may improve locoregional control in selected high-risk patients. This randomized phase II trial evaluated the role of adjuvant EBRT in reducing locoregional recurrence (LRR) in high-risk resected thyroid cancer. Methods: This was a phase II randomized controlled trial comparing surgery with RAI versus surgery with RAI plus EBRT in high-risk resected thyroid cancers. Patients with resected non-medullary, non-anaplastic thyroid cancer and predefined high-risk features were randomized (1:1) between July 2013 and April 2021. Patients randomized to EBRT received 6-MV IMRT with daily IGRT to a dose of 60 Gy in 30 fractions over six weeks. The primary endpoint was locoregional recurrence. Secondary endpoints included acute and late toxicity (LENT-SOMA scale) and quality of life. Results: Seventy-two patients were randomized, with 36 assigned to each arm; five patients withdrew consent. Overall, 86.6% had pathological T4a disease and 89.6% had pathological N1a/b disease. Further, 71.6% demonstrated extracapsular nodal extension and R1/R2 resection was seen in 49.3% of the patients. With a median follow-up of 102 months, on an intention to treat analysis, LRR occurred in 19.4% of patients in the surgery + RAI arm (OR 1.376, 95% CI 0.852-2.222), and 9.7% in the Surgery+RAI+EBRT arm (OR 0.611, 95% CI 0.299-1.632). This difference was not statistically significant (p = 0.263). Logistic regression analysis did not identify any factor significantly associated with LRR. There was no significant difference in 10 year-locoregional recurrence free survival between the two arms. Grade 3 acute radiation induced toxicity was observed in two patients. At last follow up, there was one death in the entire cohort, which was non-cancer related. Conclusions: In this very high-risk, resected thyroid cancer cohort, the addition of adjuvant EBRT to surgery and RAI did not significantly decrease locoregional recurrence. The overall acute toxicity was low and if adjuvant EBRT is indicated, it can be delivered with acceptable toxicity. Clinical trial information: NCT03669432 .

Chronic Haemorrhagic Cystitis (cHC) affects 5–15% of patients after pelvic radiotherapy. Sodium-copper-chlorophyllin, a semi-synthetic chlorophyll derivative, has shown promise in preclinical models. The phase II CLARITY trial evaluated oral chlorophyllin for radiation-induced cHC. This prospective, single-centre, single-arm phase II trial (NCT05348239) enrolled adults with grade 2–4 haematuria persisting ≥ 3 months after pelvic radiotherapy. Participants received chlorophyllin 750 mg orally daily for 12 weeks. The primary endpoint was objective response rate (ORR), including complete (CR) and partial responses (PR). Secondary endpoints were safety, quality of life [Bladder Cancer Index (urinary function, bother) and EORTC QLQ-C30 (global health, summary score)] and exploratory proteomics. Twenty-four patients were enrolled (cervical cancer 15, rectal 5, prostate 4). Baseline haematuria was CTCAE grade 2 in 6 (25%), grade 3 in 17 (71%), and grade 4 in 1 (4%) patient. In the intention-to treat analysis, the ORR was 70.8% (17/24; 95% CI 65%–83%;) with 9 CR and 8 PR, with a median time to response of 67 days and median response duration of 10 months. The per-protocol ORR was 80.9% (17/21). Chlorophyllin was well tolerated with no discontinuations and no severe adverse events. Side effects included greenish discolouration of stools in 79% and nausea in 16% patients. Significant improvements were noted for urinary function and bother and EORTC QLQ-C30 global health and summary scores. Proteomics suggested modulation of complement, coagulation, inflammatory, oxidative stress, and repair pathways. Oral chlorophyllin showed encouraging response in radiotherapy-related haemorrhagic cystitis with favourable tolerability and quality of life gains. These findings support randomised trials to confirm efficacy and durability.

PURPOSE:To evaluate prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) kinetics following PSMA-positron emission tomography (PET) and magnetic resonance (MR) guided stereotactic body radiation therapy (SBRT) and short-term androgen deprivation therapy with dominant intraprostatic lesion (DIL) boost in localized prostate cancer. METHODS AND MATERIALS:This prespecified analysis from the phase 2 PROBE trial (IRB approval: IEC 900917) included patients with intermediate- or high-risk prostate cancer treated with 5-fraction SBRT (36.25 Gy to prostate; 40 to 42.5 Gy to PSMA/MRI-defined DIL) and 6 months of androgen deprivation therapy. PSA kinetics relied on 3-monthly PSA levels. Longitudinal metabolic response, based on the adapted PET Response Criteria in Solid Tumors, was assessed using 68Ga-PSMA-PET/computed tomography done at SBRT completion, 3 to 6 months, and 9 to 12 months after SBRT completion. Cumulative genitourinary/gastrointestinal toxicities were reported per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. RESULTS:Thirty enrolled patients (54% intermediate risk, 46% high risk) were included. A PSA <0.1 ng/mL was achieved in 79% of patients at 6 months and 50% at 12 months. The mean maximum standardized uptake value (SUVmax) decreased from 12.2 (range, 4.0-39.6) pretreatment to 3.2 at 3 to 6 months and 1.8 at 9 to 12 months. Complete response (CR) rates increased from 17% at SBRT completion to 48% at 3 to 6 months and 65% at 9 to 12 months. Patients achieving CR at 3 to 6 months reached a lower mean PSA (0.04 vs 0.3 ng/mL, P = .009). Those with PSA <0.1 ng/mL at 6 months were more likely to attain CR at 12 months (76% vs 28%, P = .003). An early standardized uptake value (SUV) "flare" was observed in 4 (14%) patients, resolving by 9 to 12 months. No National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3 genitourinary/gastrointestinal toxicity was seen. CONCLUSIONS:PSMA-PET and MR guided prostate SBRT with DIL boost achieved deep PSA nadirs, gradual PSMA kinetics, and a favorable safety profile. About 80% of patients achieved a PSA <0.1 ng/mL at 6 months, with two-thirds achieving CR by 12 months post-SBRT. Achieving a PSA <0.1 ng/mL could potentially predict PSMA-CR. Early PSMA-CR at 3 to 6 months may predict durable PSA response and warrants further evaluation as a biomarker for risk-adapted strategies in localized prostate cancer.