Pembrolizumab has shown manageable safety and modest antitumor activity when used as a single agent in participants with metastatic castration-resistant prostate cancer (mCRPC). Preclinical evidence suggests that lenvatinib, a vascular endothelial growth factor-targeted agent, inhibits angiogenesis and cell migration in prostate cancer. Safety and efficacy of pembrolizumab plus lenvatinib in participants with docetaxel-pretreated mCRPC were evaluated in cohort E of the phase 1b/2 KEYNOTE-365 study. Eligible adults with confirmed mCRPC, Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1, and prior docetaxel treatment for mCRPC received pembrolizumab 200 mg intravenously every 3 wk, for ≤35 cycles, plus oral lenvatinib 20 mg daily, continuously from day 1 of cycle 1, unless specific discontinuation criteria were met. Primary endpoints were prostate-specific antigen (PSA) response rate; objective response rate (ORR), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) v1.1, by blinded independent central review; and safety. A total of 39 participants received treatment, with a median follow-up of 9.7 mo (interquartile range, 8.5-11.3). Confirmed PSA response rate was 34% (95% confidence interval [CI], 20-51). ORR for participants with RECIST-measurable disease was 36% (95% CI, 18-57). Treatment-related adverse events (AEs) of any grade occurred in 92% of participants and grade 3-5 treatment-related AEs occurred in 62% of participants. Two participants died of non-treatment-related AEs (acute kidney injury and unspecified death). Clinical trial registry: NCT02861573.

Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. ClinicalTrials.gov Identifier: NCT04571840

83 Background: Darolutamide has authorisation for treatment of non-metastatic Castrate Resistant Prostate Cancer (nmCRPC) based on the ARAMIS trial. The RECORD Study is a prospective real-world evaluation (RWE) of clinical outcomes in patients with nmCRPC treated with darolutamide in the UK. The study will improve understanding of treatment response and duration as well as inform regarding the use of next generation imaging (NGI) and effects of concomitant medication. Methods: Patients were enrolled from 19 centres over a 3-year period from November 2020. Data cut-off was 16 September 2024. Disease characteristics of patients and efficacy up to 12 months (m) after initiation of darolutamide are evaluated. Descriptive statistics will be used for patient demographics. Results: 257 patients were analysed with a median age of 77 (range 52-94) years (y). 52% have a Gleason score ≥8. 30 patients (11.7%) had NGI prior to initiation of darolutamide and 41 (15.8%) were on anticoagulant/antiplatelet medication. ECOG 0:35%, 1:59% and 2:6.2%. Median pre-treatment PSA was 9.7ng/mL and pre-treatment PSA doubling time (PSAdT) was 5 months. The greatest reduction in median PSA values was seen within the first 3m on darolutamide but was still decreasing slightly at 12m. PSA response was as follows: PSA 50 reduction at 3, 6, 9 and 12 months was 74%, 77%, 75% and 73% respectively and PSA 90 reduction at 3, 6, 9 and 12 months was 28%, 38%, 43% and 42% respectively. No differential effect on PSA reduction was seen with Gleason score (<8, ≥8), PSAdT≤6m or >6m, previous treatment (RT or prostatectomy), anticoagulant/antiplatelet medication or those who had NGI. Median duration of treatment on darolutamide did not significantly differ (p=0.067) in patients with PSAdT>6m (104 patients) compared to those with PSAdT≤6m (135 patients). 46 patients (17.9%) have come off treatment within 12m of initiation: 26 (10.1%) disease progression, 8 (3.1%) toxicity (most frequent being fatigue and diarrhoea), 12 other unrelated causes including 1 death. Conclusions: This RWE shows that patients with nmCRPC in clinical practice have comparable outcomes to the ARAMIS trial. Response rates, tolerability and discontinuation rates are similar and in particular only 3.1% discontinuing treatment due to toxicity. Gleason score >8; PSAdT and the use of NGI had no differential impact on PSA response. This is valuable RWE enabling optimisation of treatment in nmCRPC.

148 Background: More efficacious treatment options are needed to extend survival and disease control for pts with mCRPC whose disease progressed after treatment with docetaxel. The PD-1 inhibitor pembro has shown manageable safety and limited antitumor activity in pts with mCRPC. Preclinical evidence suggests the VEGF/TKI inhibitor lenva inhibits angiogenesis and cell proliferation in prostate cancer. In cohort E of the phase 1b/2 KEYNOTE-365 study (NCT02861573), the safety and efficacy of pembro + lenva was evaluated in pts with docetaxel-pretreated mCRPC. Methods: Eligible pts were aged ≥18 years with confirmed mCRPC, an ECOG PS of 0 or 1, and prior treatment with docetaxel for mCRPC. Prior treatment with 1 other chemotherapy for mCRPC and ≤2 next-generation hormonal manipulations were allowed. Pts received pembro 200 mg IV Q3W for up to 35 cycles plus lenva 20 mg PO QD continuously from day 1 of cycle 1, unless specific withdrawal or discontinuation criteria were met. Primary end points were prostate-specific antigen (PSA) response rate, objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR), and safety. Secondary end points included duration of response (DOR) and disease control rate (DCR: CR and PR of any duration and SD or non-CR/non-PD of ≥6 months) per RECIST v1.1 by BICR, radiographic progression-free survival (rPFS) per PCWG3-modified RECIST v1.1 by BICR, and overall survival (OS). Results: Of 39 treated pts, median age was 67 years (range, 55-84), 64% had RECIST v1.1–measurable disease per BICR, and 59% had an ECOG PS of 1. At data cutoff (January 25, 2023), 64% pts had discontinued study treatment, 31% due to PD; 36% pts had ongoing treatment. Median time from first dose to data cut-off was 9.7 months (range, 7.4-15.2). Confirmed PSA response was 34% (95% CI, 20-51 [13/38 pts]) for pts with a baseline PSA measurement. ORR for pts with RECIST v1.1–measurable disease was 36% (95% CI, 18-58 [9 PR]). Median DOR was not reached (NR; range, 2.1+ to 6.9+ months); 3 pts had a response duration of ≥6 months. DCR for all pts was 51%. Median rPFS was 7.9 months (95% CI, 4.1-NR); estimated 12-month rPFS rate was 35%. Median OS was 9.4 months (95% CI, 8.4-NR); estimated 12-month OS rate was 37%. Treatment-related AEs (TRAEs) occurred in 92% of pts; most common (≥30%) were hypertension (51%), hypothyroidism (44%), fatigue (38%), diarrhea (36%), dysphonia (31%), and weight decreased (31%). Grade 3-5 TRAEs occurred in 62% of pts and most common (≥20%) were hypertension (36%) and fatigue (21%). Two pts died of AEs (acute kidney failure and death), but neither were treatment related. Conclusions: Pembro + lenva demonstrated promising and durable antitumor activity in selected pts with docetaxel-pretreated mCRPC. Safety was generally consistent with the individual profiles and for the combination of these agents. Clinical trial information: NCT02861573 .

519 Background: Muscle-invasive bladder cancer (MIBC) is managed with radical cystectomy or (chemo)radiotherapy ((C)RT), CRT offers the chance of cure alongside organ preservation. Patients presenting with MIBC are often elderly and frail, with comorbidities precluding cystectomy and systemic treatment. We report outcome data for our institution of patients treated with radical (C)RT. Methods: Patients with T2-4N0 MIBC diagnosed between December 2014 and December 2021 were retrospectively identified from the radiotherapy planning system. Baseline demographic, clinical and follow up data were collated from electronic patient records. Results: 54 patients were identified. Mean patient age was 78.5 (range 47 – 94); 51 patients had urothelial cancer and 3 squamous cell carcinoma. 20 patients had evidence of carcinoma in situ (CIS) at diagnosis. 19 patients had neoadjuvant chemotherapy (NACT) (13 patients had cisplatin-gemcitabine, 6 patients had carboplatin-gemcitabine). 12/19 patients completed 3 cycles of NACT, 7 patients received 1-2 cycles. 24/54 patients had concurrent chemotherapy (6 patients receiving mitomycin-5-FU, 17 weekly gemcitabine and 1 weekly cisplatin). 14/24 patients completed concurrent chemotherapy as planned. Of the 24 patients treated with CRT, 18 had NACT. 12 patients received 64 Gy 32 fractions, 2 received 60 Gy 30 fractions, and 40 received 55 Gy 20 fractions. All except 1 patient completed the prescribed course. With a median follow up of 9.4 months (range 0.7-79 months), 3-year overall survival was 43% for all patients; 63% with CRT and 21% with RT alone (log-rank test p=0.0052 HR 3.15 (95% CI 1.48-6.7)). At 3 years 49% were free of recurrence (distant or local); 72% with CRT and 25% with RT alone (log-rank test 0.0079 HR 3.12 (95% CI 1.38-7.01)). 3yr OS and % free of recurrence were not impacted by the presence of CIS. OS was 46% with CIS and 41% without (log-rank test p=0.6649); 3yr % free of recurrence was 43% with CIS and 49% without (log-rank test p=0.4055). Median time to recurrence with CIS was shorter at 13.3 months vs 26.1 months. Conclusions: Radical radiotherapy to the bladder is an effective option for the treatment of MIBC and should be routinely discussed with patients. Patients should be treated with CRT as opposed to RT alone as both OS and RFS are significantly improved. Ensuring patients are fit to receive systemic treatment alongside RT may require prehabilitation in this elderly and more co-morbid group.

Background: Prostate cancer is a common malignancy with rising incidence in Western countries such as the United Kingdom. In localised disease there are a variety of curative treatment modalities. Patients can be referred for surgery, or for a combination of hormonal therapies and radiotherapy (external beam radiotherapy or brachytherapy). Each treatment option comes with side effects and in the case of radiotherapy one potential complication is bowel toxicity from radiation exposure. New technologies are being developed to try and mitigate the side effects and long term morbidity of this treatment, and to expand access to radiotherapy for patients who may previously have been excluded (i.e those with inflammatory bowel disease). Rectal Spacers are absorbable polyethylene glycol hydrogels injected into the perirectal space. These position the anterior rectal wall away from the prostate, subsequently minimising radiation dose to the rectum. Rectal Spacers have been introduced to National Healthcare Service (NHS) practice as part of the Innovation and Technology Payment (ITP) programme, however, their use is now under review. Methodology and Results: In this editorial we conduct a narrative review of some of the available evidence for Rectal Spacers, discuss their utilization within the NHS and the barriers to their wider use. We also explore preliminary dosimetry and quality of life data for use of Rectal Spacers in our centre where we have been part of the NHS ITP programme. Dosimetry data and Quality of life questionnaires were gathered from 22 treated patients and 11 matched controls. This indicated lower radiation doses to the prostate in those treated with Rectal Spacers. Conclusion: Rectal Spacers are an effective method to reduce radiation dose to the prostate in men treated for localised prostate cancer, however, their use remains under review in the NHS and there are a variety of barriers to upscaling their use.

52 Background: Prostate cancer is the most common solid malignancy in men. Despite advances in radical management, a proportion of patients develop castrate resistant metastatic disease (mCRPC). Management options in mCRPC include the novel hormones Enzalutamide (E) or Abiraterone Acetate (AA). There is limited knowledge of clinical factors suggesting improved response to either E or AA to guide clinician choice. Systemic inflammation caused by tumor activity may predict response to E or AA. The NLR is a marker of systemic inflammation which has been assessed previously. We present findings from a single institution evaluation of NLR for E and AA. Methods: Men receiving E or AA for mCRPC between March 2018 - February 2020 at our institution were identified. Baseline characteristics and pre-specified metrics including hematology, age and disease burden as well as time on treatment and survival data were retrospectively taken from hospital systems and collated into a single dataset. Time on treatment was used as a surrogate for progression free survival (PFS). Patients could switch therapies if they developed dose limiting toxicity within 3 months of treatment as per UK guidelines. AUROC curve analysis was applied to determine NLR cut off for E and AA cohorts specific for PFS. Results: 128 patients are included in the final analysis; 65 patients received E, 63 AA. Cohorts were well balanced with a median age at initial treatment of 75 (range 46-102) for AA and 74 (range 48-91) for E. The median Gleason score for AA was 8 and 9 for E. Patients receiving AA were more likely to have greater than 3 bone metastases (85% vs 74%). Patients receiving E were more likely to have visceral disease, 13% vs 10%. NLR cutoff, determined by AUROC curve analysis was 3.09 for E with an AUC of 0.782 (p <0.001). For AA, NLR cutoff was 3.1 with a non-statistically significant AUC of 0.588 (p=0.704). Median PFS was 239 days (range 13-1997) for E, 175 days (range 22-2037) for AA. Conclusions: The data does not support the hypothesis that NLR can be used to determine between the therapeutic option of E or AA in individual patients. Regardless of NLR, both E and AA remain good therapeutic options for men with mCRPC. This single institution real world data provides evidence of the role of NLR in determining response to novel hormone agents in the mCRPC setting for patients commencing E. No statistically significant NLR could be calculated for patients receiving AA. Although well balanced, in this non-randomized population, patients with multiple bony metastases were more likely to receive AA and those with visceral metastases, E. It is possible that this imbalance explains the lack of statistical significance in the AA cohort. We aim to expand our study cohort and evaluate OS and other potential metrics including the effects of tumor heterogeneity on the prognostic value of NLR.

216 Background: Prostate cancer is a common condition with varied pathologies based on stage, grade and presenting PSA allowing non-metastatic cases to be risk stratified at presentation. There is an evidence base for the use of Androgen Deprivation Therapy (ADT) combined with radical radiation showing a survival benefit but with an increase in patient morbidity. Prostate cancer risk stratification can be used to guide ADT therapy duration to reduce toxicity but it is unknown how closely these guidelines are followed internationally. Methods: A cross sectional survey collecting data on 15,255 patients with prostate cancer was conducted across 5 European countries and Japan. Data was interrogated to provide real-world evidence for ADT prescribing in combination with radical radiotherapy treatment and compared against the available evidence base and international best practice guidelines. Results: 3,393 patients were included in data analysis; 53% were high risk, 35% intermediate, and 12% low risk cases. 48% of patients were ages 71-80yrs with 10% being aged over 80. Data, including proposed length of hormone treatment was available for 2,832 patients. Concordance to the evidence base was good for high- and low-risk prostate cancer patients (64% and 96% respectively) but there was more disparity in the intermediate risk group with a concordance rate of only 28%. Conclusions: The data was robust enough to be interrogated and produce meaningful results. Concordance to the evidence base was high in both high and low risk disease although there was a tendency towards over-treatment in both these groups in some of the countries included. There was significant disparity in the intermediate risk group with evidence of both over- and potential under-treatment across all countries. Any potential over treatment with ADT needs to take account of the known evidence base and the potential for bone and metabolic toxicities. The data suggests that guidelines offering greater clarity on the role of ADT in intermediate risk prostate cancer may be beneficial.

131 Background: In primary treatment of localised prostate cancer, minimally invasive ablative therapies such as HIFU aim to achieve cancer control whilst offering a potentially favourable toxicity profile. At 5 years median follow up, 12% of patients treated with focal HIFU require salvage therapy. PROMS using Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC‐CP) provide a validated and clinically relevant tool to assess and quantify side effects from pelvic radiotherapy. There is limited data on late toxicity using PROMs with salvage radiotherapy in this setting. Methods: Retrospective analysis from prospectively collected data of 28 patients who received salvage radiotherapy at our institution 2010-2018 was performed. Late bowel and urinary toxicity measured by EPIC-CP is reported. Results: Gleason score at diagnosis: 3+3 4/28; 3+4 22/28; 4+3 2/28. HIFU treatment received: focal: 9/28; whole gland: 6/28; focal and redo focal: 7/28; focal and redo whole gland: 1/28; whole gland and redo: 5/28. All patients had mpMRI and biopsy proven recurrence with median PSA 6.6 ng/ml (0.57- 30.89). Median age at radiation was 67 years (55-80). Patients received 74 Gy to the prostate and 4 patients received additional pelvic lymph node irradiation. Three men received conformal radiotherapy (multiphase technique) and 25 arcing intensity modulated radiotherapy with hormone therapy as per risk stratification. Cumulative incidence of toxicity is reported at median follow-up of 43 months (7-99). Overall urinary function: no problem 8/28; very small problem 4/28; small problem 7/28; moderate problem 5/28; big problem 4/28 Urinary Incontinence Symptom Score: 2.5/12 (0-12) Urinary Irritation /Obstructive Symptom Score: 3.1/12 (0-12) Bowel Symptom Score: 3.5/12 (0-11) Biochemical relapse has occurred in 2/28 patients. Conclusions: Functional and oncological outcomes for a greater number of patients treated with minimally invasive ablative therapies followed by salvage radiation are required, however this data suggests radiation is a well-tolerated and effective salvage option following primary HIFU.

307 Background: Despite radical treatment, a proportion of men with prostate cancer will develop localized recurrence. Intermittent LHRH analogue (LHRHa) therapy has shown equivalence to long-term hormone manipulation with reduced toxicity. The non-steroidal competitive androgen receptor antagonist, bicalutamide, offers disease control with a further reduced toxicity profile. We report our institution’s experience of intermittent bicalutamide therapy (IBT) in recurrent non-metastatic castrate sensitive disease. Methods: Patients with biochemical recurrence and non-metastatic status on conventional imaging treated with IBT April 2016-November 2017 are reported. Previous LHRHa in the radical setting was allowed if testosterone recovery had occurred. For inclusion, one full course of IBT therapy had to be completed and treatment break commenced. Dose was 150mg with all other treatment decisions were at clinician discretion. Results: 103 men were identified with 4 were excluded due to insufficient data or failure to start treatment break. Mean age at initial diagnosis was 64.5yrs and, at commencement of IBT, 71.7. Mean overall time on IBT was 47months (20 and 27 months on and off treatment respectively). The longest recorded time on IBT was 153 months. 1 patient completed 8cycles of IBT. Mean number of cycles was 2.8 (range 1-8). Mean length of treatment break reduced with successive cycles of therapy measuring less than time on treatment after cycle 4. Of 39 patients with follow up therapies recorded, 77% received continuous bicalutamide as second line therapy. Conclusions: IBT offers a valid alternative to intermittent LHRHa therapy in recurrent non-metastatic castrate sensitive prostate cancer with the advantage of an improved toxicity profile benefiting patients. Further work to assess long-term outcomes in this patient population is warranted.[Table: see text]

The 2019 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium gathered oncology professionals to San Francisco, California, on February 14–16, to discuss the latest updates in GU cancer research. There were over 4400 attendees, representing nearly 70 countries, and over 680 abstracts presented. Here, we review a selection of the research presented at the meeting, which we consider of the highest relevance to geriatric oncology.

e16528 Background: Prostate cancer is the most common solid malignancy in men and despite improving radical therapies a proportion of patients will develop castrate resistant metastatic disease (mCRPC). Therapeutic options in mCRPC include abiraterone acetate and prednisolone (AA+P), enzalutamide (E) and docetaxel (D) with limited evidence to guide clinical choice between agents. COMPACT aims to collate data from multiple data sets within one hospital to assess clinical or biochemical factors that may guide therapeutic strategy. Methods: Data was collated on all patients recorded as receiving therapy with AA+P, E or D in the metastatic castrate resistant setting from the chemotherapy prescribing and dispensing systems and the pathology system at University College Hospital, London. Individual clinical notes were reviewed to determine the reason for stopping therapies. Data was collated in one dataset and analysed to present baseline demographic data. The log-rank test was used to analyse differences in the retention rate among AA+P, E and D. Results: 598 individual treatments were identified in 441 patients. 172 patients received AA+P, 119 E and 307 D with a mean age at treatment initiation of 74.1, 76.8 and 69.5 years respectively. Of the 144 patients receiving two or more treatment lines, 62% (n = 89) received D prior to either AA+P or E. E was first line therapy in 18% (n = 26) and AA+P in 20% (n = 29). 5 (3.5%) patients transferred directly from AA+P to E and 12 (8%) from E to AA+P. Kaplan Meir estimates for time to retention show no statistically significant differences when directly comparing AA+P, E and D on univariate analysis with chi squared test (AA+P vs E = 0.3609, p = 0.558 D vs E = 0.365, p = 0.5457, D vs AA+P = 0.0136 p = 0.9072). Conclusions: The COMPACT study has confirmed that it is feasible for single institutions to retrospectively review real world data from different sources, combining it into a workable database. Patient numbers were sufficient to statistically analyse the data for specific clinical factors that may correlate to a prolonged biochemical response to AA+P, E or D therapy. The failure to detect a statistically significant difference between therapies on univariate analysis may confirm that all three are acceptable treatments in mCRPC.

Brachytherapy for prostate cancer involves placing radioactive seeds directly into the prostate, with the aim of protecting healthy surrounding tissue. This article reviews the current indications for brachytherapy treatment and the different options available. The practicalities and potential complications of treatment are also considered.

Prostate cancer is considered to be a disease of the elderly, with a median age of presentation in the UK of 66.1 Significant numbers of patients are therefore older and the management of this patient cohort can be more challenging. This article highlights some of the methods that can be used to assess the elderly prostate cancer patient and the studies relevant to making appropriate management decisions.