Radiolabelled prostate-specific membrane antigen (PSMA)-based Positron emission tomography-computed tomography (PET-CT) has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET-CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, namely Lu-PSMA has been shown to be a potential new line of treatment for metastatic castrate resistant prostate cancer. W hole-body MRI (WB-MRI) has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multi-centre studies comparing 68 Ga-PSMA PET-CT and WB-MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and urinary excretion of tracers confounding image interpretation at the vesicoureteral junction. Additionally , studies have described how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA-positive lesions . Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes it challenging to accurately monitor treatment response to ADT with PSMA-PET. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB-MRI. Emerging data supports the wider adoption of PSMA-PET and WB-MRI for diagnosis, staging, disease burden evaluation and response monitoring, though their relative roles in the standard of care management of patents is yet to be fully defined.. Key points• Next-generation imaging techniques have been found to affect prostate cancer disease state classifications as their increased sensitivity can result in stage migration.

e24086 Background: Immune checkpoint inhibitors (ICIs) are well established in the treatment of metastatic renal cell (mRCC) and urothelial carcinomas (mUC). The profile of ICI immune-related adverse events (irAEs) is well described, however, data on timings of toxicity and irAEs occurring at ≥12 months are lacking. Methods: A single-site retrospective audit of mRCC and mUC patients receiving ICI-based therapy for ≥12 months between January 2014 and December 2022. ICI-based therapies included monotherapy and combination therapy with other ICIs or anti-VEGF tyrosine kinase inhibitors (TKIs). Best response to ICI-based therapy and irAEs were described. Results: 199 patients received ICI-based therapy, of which 34% (68/199) received treatment for ≥12 months. Of those on therapy for ≥12 months, 44% (30/68), 25% (17/68), and 31% (21/68) were treated with ICI monotherapy, combination with other ICIs, and TKIs, respectively. At data cut-off, 69% (47/68) were alive. 26% (18/68), 59% (40/68) and 15% (10/68) achieved complete response (CR), partial response (PR) and stable disease (SD), respectively. Overall, 83 irAEs were observed in 74% (50/68) of patients receiving therapy for ≥12 months. Of these, 71% (59/83) occurred at < 12 months and 28% (24/85) at ≥12 months. Corticosteroid therapy was required in 31% (18/59) of irAEs at < 12 months and 63% (15/24) at ≥12 months. Endocrine and cutaneous irAEs mostly occurred at < 12 months, while rheumatic irAEs were more frequently observed at ≥12 months. No ICI-related deaths occurred. At ≥12 months, 71% (17/24) of irAEs were grade 1/2 and 29% (7/24) were grade 3/4. Grade ≥3 irAEs at ≥12 months included colitis (n = 1), proctitis (n = 1), tubulointerstitial nephritis (n = 1), bullous pemphigoid (n = 1) and transaminitis (n = 3). Four patients discontinued treatment, the remainder restarted therapy after irAE resolution. All patients with late-onset grade ≥3 irAEs responded to therapy (CR in 2/7, PR in 5/7). A patient with grade 2 seronegative inflammatory arthritis with onset at ≥12 months also discontinued treatment. Conclusions: Although irAEs are less frequent after 12 months of ICI-based therapy, they remain clinically relevant requiring treatment interruption and discontinuation. Patients require ongoing safety monitoring irrespective of the duration of ICI-based therapy.

e16533 Background: Immune checkpoint inhibitors (ICIs) and anti-VEGFs, either in combination or sequentially, are the standard of care in first- and second-line (2L) setting for metastatic clear-cell renal cell carcinoma (mRCC); however, there is uncertainty about the subsequent lines. We describe real-world outcomes and safety of using anti-VEGFs such as cabozantinib (CABO), axitinib (AXI), and sunitinib (SUN) after ICIs and anti-VEGF therapies in patients (pts) with mRCC. Methods: A retrospective audit was performed on pts with mRCC treated between June 2014 and June 2022 at the St Bartholomew’s Hospital, London, UK. Baseline patient and treatment characteristics, best response, dose modifications and survival outcomes were collected. Kaplan-Meier methods were used to evaluate the progression-free survival (PFS) and overall survival (OS). Results: Overall, 188 pts with mRCC were treated. We analysed 69 pts of whom 45 (65%), 16 (23%) and 8 (12%) pts received CABO, AXI, and SUN, respectively, as subsequent treatment after prior ICIs and anti-VEG. Baseline characteristics are described. Median follow-up was 36 months (95% CI: 31.6 - 55.3). Overall, the partial response (PR) and stable disease (SD) rates were 9% and 45%, respectively. Eleven percent, 12% and 0% pts achieved PR and 53%, 25% and 31% achieved SD on CABO, SUN and AXI, respectively. In general, the median PFS was 9.9 months (95% CI: 6.5-14.2) and the median OS was 16.5 months (95% CI: 11.6-23.5). One-year PFS and 1-year OS was 36% and 51%, respectively. PFS and OS by treatment are reported. The number of pts who experienced toxicities that required dose reductions was higher with CABO (58%) and SUN (37%) than with AXI (6%). The median time to dose reduction was 2.4, 1.4, and 1.4 months for CABO, SUN and AXI. Conclusions: In our centre, CABO was the most common subsequent treatment after previous ICIs and anti-VEGF. Taking into account the retrospective and single-centre nature of the collected data these results support the activity of CABO, AXI and SUN in this setting. AXI was well tolerated with less dose modifications. [Table: see text]