Immune checkpoint inhibitors are a frontline treatment for metastatic renal cell carcinoma (RCC), one of the most common malignancies of the urinary system. However, a large proportion of patients exhibit poor responses or develop resistance, which severely limits the therapeutic efficacy and patient survival. In this study, we constructed a custom CRISPR activation library based on the top 500 genes upregulated in anti-PD-1-resistant RCC cells. Functional screening identified serum amyloid A1 (SAA1) as a critical mediator of resistance; SAA1 activation promoted immune evasion, while deficiency sensitized RCC cells to anti-PD-1 treatment. SAA1 promoted anti-PD-1 resistance both in RCC patients and in mouse models. Mechanistically, SAA1 bound to toll-like receptor 2 (TLR2) and activated the NF-κB signaling pathway, thereby inducing the formation of neutrophil extracellular traps (NETs). These NETs not only acted as physical barriers that blocked direct contact between CD8⁺ T cells and tumor cells but also promoted CD8⁺ T cell exhaustion, facilitating tumor immune evasion and resistance to immunotherapy. Both in vitro and in vivo experiments demonstrated that suppression of SAA1 significantly reduced NET formation and enhanced the efficacy of immunotherapy. In conclusion, SAA1 promotes immunotherapy resistance in RCC by driving NET formation via the TLR2/NF-κB axis and inducing CD8⁺ T cell dysfunction. Targeting SAA1 may represent a promising strategy to overcome immune resistance in RCC.

5090 Background: In the CHART trial, Rez plus ADT significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared with Bic plus ADT in patients (pts) with high-volume mHSPC (Gu et al., Lancet Oncol 2022). Here, we present updated outcomes ~5 years after the enrollment of the last pt. Methods: Pts with high-volume mHSPC and without previous chemotherapy or other localized treatment for PC were eligible to be enrolled. Pts were randomized 1:1 to receive ADT plus either Rez (240 mg) or Bic (50 mg) orally once daily. Final analysis for OS was planned after 325 deaths were reported. Results: Between Jun 28, 2018, and Aug 6, 2020, 654 pts were randomized to receive Rez plus ADT (n=326) or Bic plus ADT (n=328). As of data cutoff (Jun 6, 2025), with a median follow-up of 72.8 months (IQR 69.1-77.4), there were 141 (43.3%) deaths in Rez plus ADT group and 194 (59.1%) in Bic plus ADT group. OS was improved with Rez plus ADT versus Bic plus ADT (median 78.8 months [95% CI 68.3-not reached (NR)] vs 44.8 months [95% CI 37.1-57.4]; HR 0.59 [95% CI 0.47-0.73]; 2-sided p<0.0001). Risk of progression or death in Rez plus ADT group was reduced by 62% compared with Bic plus ADT group (HR 0.38 [95% CI 0.30-0.48]). Other efficacy outcomes also favored Rez plus ADT (Table). Rez plus ADT improved patient-reported quality of life. No new safety signals were observed. Conclusions: Rez plus ADT continued to show meaningful survival benefits with manageable toxicities after long-term follow-up, further supporting Rez plus ADT as frontline treatment for pts with high-volume mHSPC. Clinical trial information: NCT03520478 . Efficacy endpoints. Rez plus ADT (n=326) Bic plus ADT (n=328) HR (95% CI) 2-sided p-value OS, months 78.8 (68.3-NR) 44.8 (37.1-57.4) 0.59 (0.47-0.73) <0.0001 rPFS per investigator, months 81.0 (62.6-NR) 18.5 (14.8-25.7) 0.38 (0.30-0.48) <0.0001 rPFS per investigator (sensitivity analysis # ), months 58.9 (50.10-NE) 18.6 (16.30-22.90) 0.38 (0.31-0.47) <0.0001 Time to PSA progression, months NR (NR-NR) 11.0 (9.2-12.9) 0.21 (0.17-0.27) <0.0001 Time to next skeletal-related event, months 78.8 (58.9-NR) 37.7 (34.3-48.2) 0.63 (0.51-0.78) <0.0001 Time to initiation of new anti-prostate cancer therapy, months 62.4 (46.4-75.6) 15.1 (13.6-18.1) 0.32 (0.26-0.39) <0.0001 Data are median (95% CI) unless otherwise indicated. # New anti-cancer therapy and missing tumor assessments were not considered. PSA, prostate specific antigen.

PURPOSE:To evaluate oncological and functional outcomes of minimally invasive partial and radical nephrectomy (MIS-PN vs. MIS-RN) in patients with pT3aN0M0 renal cell carcinoma (RCC). MATERIALS AND METHODS:We performed a multicenter retrospective study of patients with pT3aN0M0 RCC treated with MIS-PN or MIS-RN. The primary outcome was recurrence-free survival (RFS). Secondary outcomes included de novo eGFR <60 mL/min/ 1.73 m2 (CKD-S) and <45 mL/min/ 1.73 m2 (CKD-S3b) at the new baseline (1-12 month postoperatively), as well as CKD-S at the latest follow-up (>1 year postoperatively). A 1:2 ratio propensity score matching (PSM) was applied to balance covariates, and inverse probability weighting (IPW) served as sensitivity analysis. Survival curves were estimated using the Kaplan-Meier method, and multivariable analyses (MVA) were performed to identify predictors of oncological and functional outcomes. RESULTS:A total of 303 patients were enrolled (113 MIS-PN/190 MIS-RN) with a median follow-up of 39.0 months (IQR 26.8-52.9). After PSM (66 MIS-PN/54 MIS-RN), no significant difference in RFS was observed between two groups (p=0.23). MVA revealed that surgical approach was not an independent predictor of RFS (HR: 1.00, p=1.00). Among patients with available new baseline eGFR after PSM (41 MIS-PN/37 MIS-RN), MIS-RN was independently associated with a higher risk of CKD-S (OR: 7.96, p=0.03). Among patients with available the latest follow-up eGFR after PSM (41 MIS-PN/37 MIS-RN), MIS-RN remained an independent predictor of CKD-S at the latest follow-up (OR: 7.98, p=0.03). IPW analysis yielded consistent results. Additionally, IPW identified MIS-RN as an independent risk factor for CKD-S3b at the new baseline (OR: 18.29, p<0.01). CONCLUSION:MIS-PN provided comparable mild term oncologic outcomes to MIS-RN while offering superior renal function preservation. MIS-PN may be a viable option for selected T3a RCC patients when nephron preservation is indicated.

TPS4630 Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma, accounting for 75-80% of cases worldwide and 60-85% in China. High risk ccRCC includes tumors larger than 7 cm (T2 stage) or those at advanced stages (≥T3 or N1). Surgical resection is standard, but 30% may have recurrence, with a 2-year disease-free survival rate of 68%. Neoadjuvant therapy with axitinib and toripalimab may enhance antitumor immunity and improve prognosis for high risk patients. Methods: This is an open-label, multicenter, phase III randomized controlled study to assess whether neoadjuvant axitinib plus toripalimab improves disease-free survival (DFS) compared with surgery alone in patients with ccRCC at high risk of recurrence. The study is designed to enroll 298 patients with high risk ccRCC (T2G4 or T3-4 or N1) scheduled for nephrectomy. Patients must provide an adequate tumor tissue sample at screening for molecular and immune profiling. Patients will be randomly assigned to the control group or the neoadjuvant group at a 1:1 ratio. Both groups will undergo nephrectomy, while the neoadjuvant group will additionally receive preoperative treatment with axitinib plus toripalimab. Axitinib will be given for 3 months, 5 mg twice daily, orally. Toripalimab will be administered at 240 mg intravenously every 3 weeks for 4 cycles (one cycle every 3 weeks). Blood samples are collected before and after neoadjuvant treatment for exploratory molecular analysis. CT or MRI assessments will be conducted after 2 cycles of medication and before surgery. Radical nephrectomy (or partial nephrectomy, if applicable) will be performed within 1-28 days after completion of neoadjuvant therapy. For both groups, if postoperative pathology meets high recurrence risk criteria per Keynote-564—specifically, T2G4, T2 with sarcomatoid differentiation, T3, T4, any T stage with lymph node metastasis, or M1 with no evidence of disease—1 year of adjuvant toripalimab is recommended according to NCCN and EAU guidelines. Eligible patients must be diagnosed as ccRCC or RCC with a predominant clear cell component through histopathological examination. Clinical staging via CT or MRI must indicate T2, while biopsy pathology should show either nuclear grade 4 or sarcomatoid differentiation, or a classification of T3-4 or N1. Additional inclusion criteria include: signed informed consent, age ≥18 and < 80 years old, adequate organ function, ECOG of 0 or 1 point. The primary endpoint is 2-year DFS, defined as the time from randomization to disease recurrence or death from any cause. Secondary endpoints include cancer-specific survival, overall survival, objective response rate, major pathological response, and safety profile. Enrollment began in April 2023, and 112 of the planned 298 patients have been enrolled. Clinical trial information: NCT05738694 .

Lactate in the tumor microenvironment (TME) is typically generated by cells exhibiting high glycolytic flux, exemplified by tumor cells. However, in glycolysis-low malignancies such as prostate cancer, stroma-derived lactate may drive noncanonical signaling and functions that remain unclear. Here, we identified APCDD1+ cancer-associated fibroblasts (CAFs) as a distinct stromal population that secretes lactate into the TME in response to androgen deprivation therapy (ADT). Lactate uptake by prostate cancer cells induces androgen receptor variant 7 expression, thereby conferring resistance to ADT. Mechanistically, lactate-induced lactylation of the spliceosome component SNRPA at Lys123 (K123) enhances its recognition of cis-acting elements, increases chromatin binding, and promotes androgen receptor splicing. Targeting lactate transport with monocarboxylate transporter inhibitors effectively restores ADT sensitivity. These findings reveal a metabolic-epigenetic axis linking lactate in the microenvironment to alternative splicing regulation and suggest a promising therapeutic strategy to overcome ADT resistance.

4599 Background: Radical cystectomy (RC) was the standard of care for high-risk non-muscle-invasive bladder cancer (HR NMIBC) patients with Bacillus Calmette-Guerin (BCG)-unresponsive papillary tumors. Clinical unmet need was to explore non-surgical treatment options for patients who were ineligible for or declined RC. Our study was established to evaluate the efficacy and safety of tislelizumab combined with radiotherapy as bladder-preserving treatment for HR NMIBC patients unresponsive to BCG. Methods: This open-label, single arm phase II study enrolled HR NMIBC patients with BCG-unresponsive papillary tumors (high-grade Ta or T1 tumors without carcinoma in situ). The papillary tumors should be removed all visible lesions by transurethral resection of bladder tumor (TURBT). Within 2 weeks after TURBT, eligible patients received tislelizumab 200 mg in day 1 (D1), every 21 days for eight cycles and a total radiotherapy dose of 60-66 GY in 30-33 fractions over seven weeks. The primary endpoint was disease-free survival (DFS) rate at 12 months (defined as no reappearance of high grade or T1 tumors or clinical stage development after the therapy). Secondary endpoints were bladder-preservation rate, OS and safety. Our study estimated a DFS rate at 12 months was no less than 50% and the study would enroll 32 patients to meet the primary endpoint. Results: Between September 4, 2020, and December 11, 2024, 32 patients (26 [81.2%] men and 6 [19.8%] women) who had received a median of eleven (IQR 7-22) previous BCG instillations were enrolled. Patients received a median of 8 cycles (IQR 8–8) of tislelizumab and of radiotherapy doses of 62.0 GY (IQR 62.0–64.0) . Median follow-up was 28.8 months (19.7-43.8). The DFS rate at 12 months was 90.6% (95%CI, 79.8%-99.6%), at 24 months was 70.2% (95%CI, 50.1%-83.4%). The bladder-preservation rate at 24 months was 93.2% (95%CI, 75.4%-98.3%). The OS rate at 24 months was 100% (95%CI, 100%-100%). The OS rate at 36 months was 90.5% (95%CI, 67.0%-97.6%). Treatment-related adverse events (TRAEs) occurred in 27 (84.4%) of 32 patients, 7 (21.9%) patients had a grade 3 TRAEs. The most common 3 TRAEs were diarrhea (9.4%), radiocystitis (3.1%), leukopenia (3.1%) and liver function damage (3.1%) without grade 4-5 TRAEs. Conclusions: Our final results supported the use of tislelizumab combined with radiotherapy as a promising bladder-preserving therapy for BCG-unresponsive HR NMIBC patients who were ineligible for or decline RC. Clinical trial information: ChiCTR2000035275.

Partial nephrectomy (PN) has been performed for renal masses ≥7cm with promised oncological outcome, whereas their functional and volumetric changes remain unclear. This study aims to evaluate renal functional and volumetric changes after PN for renal masses ≥7cm and compare these outcomes with those of with smaller renal masses(<7cm). A total of 107 patients with renal masses ≥7 cm who underwent PN with sufficient data were included. PN patients with renal masses <7 cm were enrolled as controls. The acute ipsilateral renal dysfunction (AIRD) spectrum score, recovery from ischemia and annual ipsilateral renal parenchymal volume (RPV) decrease was used to reflect short, mid, and long-term functional/volumetric changes, respectively. The median tumor size in the study group was 8cm (interquartile range [IQR]: 7.5-9cm) with a median R.E.A.N.L. score of 10(IQR: 8-10) and the median ischemia time was 30 minutes, which were all significantly higher than those in the control group. Although the study group demonstrated lower ipsilateral renal parenchymal volume preservation (81.5

744 Background: There are limited 1L therapy options for cisplatin-ineligible patients with locally advanced or metastatic UC (la/mUC), indicating an unmet need for novel treatment strategies. Sac-TMT (MK-2870/SKB264) is a TROP2-directed ADC with a unique bifunctional linker that maximizes delivery of a novel belotecan-derived topo I inhibitor payload to tumor cells, that has shown promising antitumor activity in several tumor types, including as monotherapy in UC (Ye, D, et al. J Clin Oncol 2025;43[suppl 5]:796). We present efficacy and safety data for cohort B in 1L cisplatin-ineligible pts with la/mUC from the phase 2, open-label 2870-002/SKB264-II-06 study (NCT05642780) evaluating sac-TMT + pembro in pts with select solid tumors. Methods: Eligible pts in cohort B were aged ≥18 y, previously untreated, cisplatin-ineligible with la/mUC. Pts with prior adjuvant or neoadjuvant platinum-based therapy or nivolumab were eligible if they had disease recurrence >12 mo after completing therapy. Pts received sac-TMT 4 or 5 mg/kg IV (non-randomized) on days 1, 15, and 29 of each 42-day cycle + pembro 400 mg IV on day 1 of each 42-day cycle for up to 2 years until PD or unacceptable toxicity. Primary endpoints were safety and ORR per RECIST v1.1 by investigator assessment. Secondary endpoints included DCR, DOR, and PFS by investigator assessment. Results: As of May 21, 2025, 40 pts were treated with sac-TMT (26 pts at 4 mg/kg and 14 pts at sac-TMT 5 mg/kg) + pembro. Median follow-up was 14.5 (range, 11.6–21.8) mo. Median age was 66.5 y, 37 pts (93%) were Asian, and 24 (60%) had upper tract UC. Confirmed ORR was 68%, median DOR was 15.4 mo, and median PFS was 11.2 mo (Table). 39 pts (98%) experienced treatment-related AEs including 23 (58%) with grade 3 or 4 treatment-related AEs. Anemia (15%), decreased neutrophil count (15%), and stomatitis (10%) were the most common (incidence ≥10%) grade 3 or 4 treatment-related AEs. No treatment-related deaths occurred. Conclusions: Sac-TMT + pembro showed promising antitumor activity at both 4 and 5 mg/kg in previously untreated, cisplatin-ineligible pts with la/mUC, with a manageable safety profile consistent with that of the individual treatment components. Further studies are warranted. Clinical trial information: NCT05642780 . Outcome Sac-TMT 4 mg/kg + Pembro 400 mgn = 26 Sac-TMT 5 mg/kg + Pembro 400 mgn = 14 Total N = 40 Confirmed ORR, % (95% CI) 65 (44.3–82.8) 71 (41.9–91.6) 68 (50.9–81.4) DCR, % (95% CI) 89 (69.8–97.6) 86 (57.2–98.2) 88 (73.2–95.8) BOR, n (%) CR 0 (0) 1 (7) 1 (3) PR 17 (65) 9 (64) 26 (65) SD 6 (23) 2 (14) 8 (20) PD 1 (4) 1 (7) 2 (5) No assessment a 2 (8) 1 (7) 3 (8) Median DOR, mo (range) 15.4 (3.6–15.4) NR (2.0–17.7+) b 15.4 (2.0–17.7+) b Median PFS, mo (95% CI) 10.9 (5.7–NE) NR (3.7–NE) 11.2 (5.8–NE) NE, not estimable; NR, not reached. a Includes pts without post-baseline assessment on data cutoff date. b “+” indicates no event by time of last disease assessment.

In the immunotherapy era, tyrosine kinase inhibitor (TKI) monotherapy is still commonly used for patients with metastatic renal cell carcinoma (RCC) in clinical practice. Prospective evidence on immunotherapy plus tyrosine kinase inhibitor (TKI) after first-line TKI treatment failure is scarce. This study evaluated the efficacy and safety of camrelizumab plus apatinib in this setting. In this single-arm, two-center phase 2 study, patients with metastatic clear cell RCC who had failed first-line TKI treatment were enrolled. Camrelizumab 200 mg once every 2 weeks and apatinib 250 mg once daily were continuously administered until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Between August 2020 and January 2024, 41 patients were enrolled and treated. Median age was 57.0 years (range, 36–81), and 34 (82.9

Making the decision between technically challenging partial nephrectomy (PN) and radical nephrectomy (RN) in patients with complex renal cell carcinoma (RCC) remains a significant challenge for urologists. Rapid glomerular filtration rate (GFR) decline (annual decline >3 mL/min/1.73 m²) after RN is considered an abnormal renal function state, and if this risk can be predicted preoperatively, PN may be pursued even when technically demanding. We retrospectively analyze contrast-enhanced computed tomography images and clinical data from 1621 patients across multiple centers. A multimodal deep learning model is developed to predict rapid GFR decline after RN. The model achieves an area under the curve of 0.788-0.873 in external test sets. It stratifies patients into high- and low-risk groups with significantly different risks of chronic kidney disease progression. Here we show that the model demonstrates potential for assisting treatment decisions in patients with complex RCC for whom PN is challenging but feasible.

Comparative data on stereotactic body radiotherapy (SBRT) in oligometastatic renal cell carcinoma (RCC) is lacking. This single-center, phase 2 non-randomized controlled trial enrolls patients with treatment-naive oligometastatic RCC. Patients choose to receive sunitinib alone (control arm, n = 24) or plus SBRT (SBRT arm, n = 24). The primary endpoint, objective response rate (83.3% vs. 29.2%; p < 0.001), is higher in the SBRT arm. With a median follow-up of 40.6 months, the 1-year local control rate is 91.5%. Progression-free survival (PFS) is significantly longer in the SBRT arm (17.3 vs. 6.3 months; p = 0.036). Post hoc multivariable analysis shows that SBRT significantly prolongs PFS (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.21-0.84; p = 0.015). Grade 3 toxicities are similar (54.2% vs. 50.0%, p = 0.773). The SBRT arm shows a trend toward better quality of life. These suggest potential benefit of SBRT in oligometastatic RCC, requiring further validation by phase 3 trials. The trial is registered at Chictr.org.cn (ChiCTR1800017136).

4526 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of all kidney cancers, however, the effect of systemic chemotherapy is limited. We report the first results of a single-arm, phase 2 study (NCT05220267) evaluating the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor) combined with sintilimab (a monoclonal antibody against programmed cell death protein 1) as first-line treatment in patients with advanced nccRCC. Methods: Patients with histologically confirmed advanced nccRCC and measurable disease per RECIST v1.1 who had not previously received systemic therapy were received anlotinib (12 mg qd, d1-14, repeated every 21 days) plus sintilimab (200 mg IV Q3W) till disease progression or intolerant toxicity. The primary endpoint is progression-free survival (PFS); secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From April 2022 to January 2024, 44 patients were enrolled with a median age of 46 years (range: 18-79), 13 (29.5%) had Fumarate deficient RCC, 10 (22.7%) had Papillary RCC, 9 (20.5%) had TFE3 rearranged RCC and 12 (27.3%) were unclassified. Among these participants, 44 patients were evaluable. 95.5% were IMDC intermediate- or poor-risk, 72.7% had prior nephrectomy and 97.7% had synchronous metastatic disease. ORR and DCR were 56.8%（95%CI 41.6-72.1）and 86.4%（95%CI 75.8-96.9）, respectively.≥1 and ＜1 Combined Positive Score of PD-L1 expression were observed in 50% (22/44) and 38.6% (17/44) patients respectively, and the ORR was 72.7% (95%CI:52.2-92.9) and 41.2% (95%CI: 15.1-67.3) in the two groups. As of November 13, 2024, median follow-up time was 17.5m (95%CI 14.9-20.1). The median PFS was 13.6m (95%CI 8.6-18.6). Treatment-related grade 3/4 adverse events were observed in 22.7% (10/44) of the patients, encompassed proteinuria (3 patients, 7%), hyponatremia (2 patients, 4%), hypertension (1 patients, 2%), hepatic insufficiency (1 patients, 2%), fatigue(1 patients, 2%), rash (1 patients, 2%), decreased lymphocyte count (1 patients, 2%). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Our results showed promising efficacy and acceptable toxicity of anlotinib plus sintilimab for patients with advanced nccRCC. Clinical trial information: NCT05220267 .

e16511 Background: Currently, targeted agents and immunotherapy are applied to local-regional recurrent renal cell carcinoma (LRRCC). The combination with systemic therapy and stereotactic radiotherapy (SBRT) is worth exploring. In the present study, we aimed to investigate the efficacy and safety profile of sintilimab plus axitinib combined with SBRT in the treatment for LRRCC. Methods: This was a single-arm, phase II study enrolled LRRCC patients (pts), for whom the SBRT can be safety applied for all the recurrent lesions visible on imaging. Eligible pts received sintilimab (200mg, day 1) and axitinib (5mg, bid, day 1-21) in a 21d cycle. SBRT (35-45Gy/5 fractions) was performed before the third administration of sintilimab. The primary endpoint was progression-free survival (PFS). Results: From Oct 2021 to Jan 2024, 19 pts with a median age of 58 (range: 33-74) were enrolled. Among them, 9 (47.37%) pts had clear cell carcinoma. Nine (47.37%) pts were IMDC intermediate (7 pts) or high risk, and 8 (42.11%) pts recurred in less than 1 year after surgery. Seven(36.84%) pts received at least one prior systemic therapy. Four (21.05%) pts had recurrence in the renal fossa, while 3(15.79%) pts in retroperitoneal lymph node, 2(10.53%) pts in retroperitoneal lymph node with renal fossa and 10(52.63%) pts in intra-abdominal soft tissue. With a median follow-up of 9.5 months (range: 3.0-27.1m), 18 pts were evaluable for response. The median tumor volume was 37.47cc (range: 2.44-493.19cc). The overall response rate was 55.56% with 4 complete responses and 6 partial responses per RECIST v1.1. The median time-to-response was 5 months. The local control rate and the disease control rate were 100% and 94.44%, respectively. The median PFS was not reached, and the 9-month PFS rate was 94.44%. All 19 pts were evaluable for toxicity. Any-grade treatment-related adverse events (TRAEs) occurred in 16(84.21%) pts. The most common TRAEs were albuminuria (8/19; 42.11%), nausea (8/19; 42.11%), hypertension (7/19; 36.84%), and diarrhea (7/19; 36.84%). Grade 3 or higher TRAEs occurred in 6/19(31.58%). Conclusions: Sintilimab plus axitinib combined with SBRT showed promising antitumor activity and manageable toxicity in pts with LRRCC. Clinical trial information: ChiCTR2100049523 .

Background:Low metastatic burden prostate cancer (LMBPC) is a special transitional clinical status between localized and disseminated disease, but the clinical prognostic factors and potential therapeutic interventions of those with non-regional lymph node metastases (NRLNM) remain less understood. We aim to explore the prognostic factors and investigate the potential treatment strategy for LMBPC patients with NRLNM. Methods:There were 88 patients retrospectively identified. Kaplan-Meier method and Cox proportional hazards model were used for prognostic analyses. Patients receiving non-regional lymph node (NRLN) radiotherapy (NRLN RT group) after prostate-directed local therapy were matched to patients without NRLN RT (control group) by propensity score matching (PSM). Results:The majority of patients had Gleason score >8 (61.4%), retroperitoneal metastases (93.2%), upward NRLNM (78.4%) and hormone-sensitive prostate cancer (HSPC) (68.2%) at diagnosis. Patients with upward NRLNM showed better survival outcome (75.4 vs. 32.8 months, P=0.04). HSPC [hazard ratio (HR) =0.32, P=0.003], bone metastases (HR =3.79, P<0.001), androgen-receptor-axis-targeted agents (ARATAs) (HR =0.40, P=0.007), and notably, NRLN RT (HR =0.23, P=0.001) were independent prognostic factors of overall survival (OS). The median follow-up was 43.3 months. The prostate-specific antigen (PSA) response and median progression-free survival (PFS) after NRLN RT were 70.6% and 29.5 months. The 4-year OS for NRLN RT group and control group were 62% and 46% (P=0.04). After PSM, NRLN RT was still associated with improved OS (HR =0.39, P=0.04). No grade ≥3 NRLN RT-related adverse event was observed. Conclusions:Upward NRLNM was the main pattern for LMBPC with NRLNM and associated with better clinical outcome. HSPC, bone metastases, ARATAs and NRLN RT were independent prognostic factors. Applying cytoreductive RT to NRLNM may benefit LMBPC patients. Further studies are still needed.

To determine the optimal time for salvage radiotherapy (SRT) after radical prostatectomy (RP) with or without hormone therapy (HT) and/or whole pelvic radiotherapy (WPRT) by balancing radiotherapy-related toxicity and tumor control. Data from 155 prostate cancer (PCa) patients who received salvage radiotherapy (SRT) following radical prostatectomy (RP) between April 2015 and February 2021 were analyzed. Early salvage radiotherapy (ESRT) was defined as prostate-specific antigen (PSA) ≤ 0.5 ng/ml before radiotherapy. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events, version 5.0. Survival outcomes were analyzed using the Kaplan–Meier estimates and Cox proportional-hazards regression. Progression-free survival (PFS) and overall survival (OS) were assessed. Patients who received ESRT had significantly higher 5-year PFS (83.8

BACKGROUND:The underexplored potential of PD-L1 blockade in advanced renal cell carcinoma highlights an urgent need for novel agents. This trial aimed to compare benmelstobart (a novel PD-L1 inhibitor) plus anlotinib with sunitinib as first-line treatment for advanced renal cell carcinoma. METHODS:ETER100 was a multicentre, randomised, open-label, phase 3 trial conducted at 37 medical sites in China. We included patients aged 18-80 years, who had previously untreated, advanced, clear-cell renal cell carcinoma, and an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned (1:1) patients to receive either benmelstobart (intravenous, 1200 mg, once every 3 weeks) plus anlotinib (oral, 12 mg, once daily for the first 2 weeks of a 3-week cycle) or sunitinib (oral, 50 mg, once daily for the first 4 weeks of a 6-week cycle) until disease progression, unacceptable toxicity, investigator's decision, or patient withdrawal. Randomisation was done centrally with stratified block randomisation (block size 4) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk. The primary endpoint was progression-free survival as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumours version 1.1 in the full analysis set (ie, randomly assigned patients who received at least one dose of study drug without the violation of key inclusion criteria) and per-protocol set (ie, randomly assigned patients who received at least one cycle of protocol treatment without major protocol violations and had at least one efficacy assessment). In this Article, we report the results of a prespecified interim analysis. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT04523272. FINDINGS:Between Aug 25, 2020, and Feb 6, 2023, we assessed 687 patients for eligibility, 531 (77%) of whom were randomly assigned to receive either benmelstobart plus anlotinib (266 [50%] patients) or sunitinib (265 [50%] patients). 527 (99%) patients were included in the full analysis set (263 [50%] patients who received benmelstobart plus anlotinib and 264 [50%] who received sunitinib). All patients were Chinese (400 [76%] men and 127 [24%] women), with a median age of 60 years (IQR 54-67). As of the cutoff date (Jan 31, 2024), the median follow-up was 22·8 months (IQR 15·2-29·7). In the full analysis set, median progression-free survival was significantly longer with benmelstobart plus anlotinib than with sunitinib (19·0 months [95% CI 15·3-22·8] vs 9·8 months [8·4-12·4]; hazard ratio [HR] 0·53 [95% CI 0·42-0·67]; p<0·0001). In the per-protocol set, median progression-free survival was 19·0 months (16·5-22·8) in the benmelstobart-anlotinib group versus 11·0 months (8·5-13·6) in the sunitinib group (HR 0·55 [0·43-0·70]; p<0·0001). The most common grade 3 or worse treatment-related adverse event was hypertension (occurring in 91 [34%] of 264 patients in the benmelstobart-anlotinib group vs 55 [21%] of 264 in the sunitinib group). Serious treatment-related adverse events occurred in 63 (24%) patients in the benmelstobart-anlotinib group and in 42 (16%) patients in the sunitinib group. In the benmelstobart-anlotinib group, three (1%) deaths occurred due to treatment-related adverse events (one each with cardiac-respiratory arrest, unknown reason, and renal failure) and no deaths occurred in the sunitinib group. INTERPRETATION:Benmelstobart plus anlotinib improved progression-free survival compared with sunitinib among patients with previously untreated, advanced clear-cell renal cell carcinoma. These findings suggest the potential of benmelstobart plus anlotinib as a treatment option for this population. FUNDING:Chia Tai Tianqing Pharmaceutical Group and CSCO Clinical Oncology Research Foundation. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

Objective: The aim of this study was to investigate the value of the 8th American Joint Committee on Cancer (AJCC) anatomic and prognostic stage groups for penile cancer patients and explore whether there is room for improvement. Methods: The clinical and histopathologic data from 16 centers between January 2000 and December 2021 were assessed according to the 8th AJCC anatomic and prognostic stage groups. Kaplan-Meier plots were used to estimate the disease-specific survival (DSS) of the patients. The accuracy of the staging systems was investigated using the Harrell's concordance index (C-index). Results: According to the 8th AJCC anatomic and prognostic stage groups, the 5-year DSS rates for patients with stages 0is/a, I, IIA, IIB, IIIA, IIIB, and IV disease were 100%, 99%, 86%, 81%, 66%, 34%, and 23%, respectively (p(0is/a-I)=0.8, p(I-IIA)<0.001, p(IIA-IIB)=0.5, p(IIB-IIIA)<0.001, p(IIIA-IIIB)<0.001, p(IIIB-IV)=0.004, and p(Total)<0.001). According to the modified model 1 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100%, 99%, 88%, 66%, 34%, and 23%, respectively (p(0is/a-I)=0.8, p(I-II)<0.001, p(II-IIIA)=0.002, p(IIIA-IIIB)<0.001, p(IIIB-IV)=0.004, and p(Total)<0.001). Similarly, according to the modified model 2 system, the 5-year DSS rates without survivorship overlap for patients with stages 0is/a, I, II, IIIA, IIIB, and IV disease were 100%, 99%, 86%, 66%, 34%, and 23%, respectively (p(0is/a-I)=0.8, p(I-II)<0.001, p(II-IIIA)=0.008, p(IIIA-IIIB)<0.001, p(IIIB-IV)=0.004, and p(Total)<0.001). The C-index scores of the simple modified staging systems were not inferior to those of the AJCC anatomic and prognostic stage groups. These results were confirmed by the bootstrap internal validation. Conclusion: There is still room for improvement about the 8th AJCC anatomic and prognostic stage groups. The improved models, which are more concise and convenient, have similar prediction accuracy. (c) 2025 Editorial Office of Asian Journal of Urology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

TPS307 Background: PARP inhibitors (PARPi) emerged as an promising treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutation. However, prediction of treatment response remains a challenge. Still, some patients with mutations other than BRCA1/2 responded to PARPi. Circulating tumor DNA (ctDNA) is a promising biomarker that can offer real-time insights into tumor dynamics, allowing for non-invasive monitoring of therapeutic efficacy. This study aims to assess ctDNA monitoring as a predictor of response and relapse for mCRPC patients receiving PARPi. Methods: This trial is an open-label, single-center, observational, prospective cohort study. This study intends to enroll 30 male mCRPC participants aged 18 to 75 years, who have progressed from second-line treatment at mCRPC stage and exhibit homologous recombination deficiency (HRD) or carrying DNA damage repair (DDR) gene mutations. The study involves whole blood and tumor tissue sampling for ctDNA detection, homologous recombination repair (HRR) gene testing, and whole exome sequencing. The primary outcomes include radiological progression-free survival (rPFS), objective response rate (ORR), and PSA response rate, with overall survival (OS) as a secondary outcome. The Institutional Review Board of Sun Yat-sen University Cancer Center approved this study. Recruitment is ongoing, with a target follow-up duration of 12 months and 26.7% (8/30) of the target sample size achieved. Data analysis is expected to commence in 2025 upon completion of recruitment. Clinical trial information: NCT05116579 .