tbuckley/cabot-search huggingface dataset:
The role of salvage cystectomy after prior trimodality therapy.
Authors: Nikolaos Pyrgidis, Gerald Bastian Schulz, Pietro Schilipoti, Francesco Pellegrino, Jozefina Casuscelli, Lazaros Tzelves, Davide Ciavarella, Maria del Carmen Mir, Tobias Klatte, Ramos Belinchon, Jorge Caño Velasco, Yasuhisa Fujii, Hajime Tanaka, Soichiro Yoshida, Paolo Umari, Jeremy Y.C. Teoh, Chris Wong Ho Ming, Giuseppe Simone, Riccardo Mastroianni, Marco Moschini
Journal: Journal of Clinical Oncology (2025)

781 Background: Trimodality therapy (TMT) with transurethral resection followed by radiation of the urinary bladder and chemotherapy is associated with similar long-term survival rates compared to radical cystectomy (RC) for well-selected patients. Nevertheless, salvage RC may become necessary in 10% of patients receiving TMT. We aimed to assess the perioperative and long-term outcomes of salvage RC after prior TMT through a large multinational cohort study. Methods: We included patients with pure urothelial cancer of the urinary bladder. Patients undergoing salvage RC after prior TMT due to recurrence in the urinary bladder from 11 high-volume centers were matched with a propensity score matching on a 1:1 ratio with patients without prior TMT undergoing primary RC. The two groups were adjusted for institution, age, histological status, ASA score, and surgical technique. Results: We included 108 patients (54 per group) with a median age of 74 years (IQR: 66-78). The two groups did not differ in terms of operative time (TMT: 250 versus non-TMT: 251 minutes, p = 0.9), intraoperative blood loss (TMT: 550ml versus non-TMT: 600ml, p = 0.2), and perioperative Clavien-Dindo complications (p = 0.9). At a follow-up of 16 months (IQR: 6-38), 45 (42%) deaths occurred. Prior TMT was associated with higher mortality rates in the survival analysis (log-rank test: p = 0.037). Accordingly, the progression rates were higher in patients with prior TMT (log-rank test: p = 0.047). Conclusions: Salvage RC after TMT is associated with similar perioperative outcomes compared to primary RC. Nevertheless, patients undergoing salvage RC after TMT may present worse progression rates and overall survival in the long term. Therefore, systemic therapies should be considered in patients with recurrence after TMT.
Effectiveness and safety of radium-223 in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 48 real-world studies.
Authors: Michaela Lunan, Amit D Raval, Nguyen Thi Nhan Phan, Matthew J. Korn, Vanessa Quintero, Rana R. McKay
Journal: Journal of Clinical Oncology (2025)

81 Background: Radium-223 (Ra-223) has been approved for men with mCRPC with bone metastases since 2013. However, as the treatment landscape has significantly changed in the last decade, a comprehensive understanding of Ra-223's real-world outcomes could inform on treatment choice in routine clinical practice. This systematic literature review aims to fill this gap by summarizing the real-world (RW) effectiveness and safety in men with mCRPC treated with Ra-223. Methods: Electronic databases (PubMed, Embase, the Cochrane Library, trial registers) and the past-two years of relevant conferences were searched systematically for RW observational studies examining outcomes of Ra-223 in men with mCRPC published between 2014 and March 2024. Study results of interest included Ra-223 treatment pattern, real-world overall survival (rwOS) and progression-free survival (PFS), pain response, change in alkaline phosphatase (ALP) or prostate-specific antigen (PSA), and safety outcomes (any or grade 3+ skeletal-related events, myelosuppressive adverse events). Results: From 1085 citations identified, 48 studies with 15,368 men with mCRPC met inclusion criteria. Most studies were retrospective cohorts (n=39) from Europe (n=22) and North America (NA) (n=18), with sample size ranging from 104 to 1,628. Median age mostly ranged from 68 to 76 Ten studies reported tumor burden and included ≥ 25% of cohort with 20+ metastases. Over 50% of Ra-223 cohort received prior chemotherapy in 23 studies, and 50% received prior ARPIs in 22 studies. Most studies in NA and Europe reported ≥ 55% and 64% completion of ≥ 5 cycles of Ra-223, respectively. Earlier line, no prior chemotherapy or immunotherapy, hemoglobin and neutrophils within lower standard limit were key factors associated with completion of ≥5 cycles of Ra-223. Median rwOS varied widely from 11 to 24 months with two exceptions and nearly a 1/3 rd reporting 15 months or longer. Completion of ≥ 5 cycles was associated with a 2 to 5-fold increase in the median rwOS. PFS ranged from 4.3 to 7.3 months with a median of 2 prior lines in the 7 studies reporting. 12 studies reporting pain outcomes showed a reduction in pain with varying magnitude. Of 13 studies reporting grade 3+ myelosuppression, incidence varied from 1-22%. Out of 14 studies reporting fractures, the incidence was &lt;10% in most studies (N=12) with trends toward lower rates with bone health agent (BHAs) use. Conclusions: This is the most up-to-date and comprehensive review of the effectiveness and safety of Ra-223 in a modern era with more widespread use of ARPIs post landmark ALSYMPCA trial for Ra-223. Findings highlight the survival benefits of early use of Ra-223 with the completion of 5 or more cycles, along with a favorable safety profile and low rates of fracture when guideline recommended BHAs are used.
Efficacy and safety of ifosfamide and mesna in metastatic castration-resistant prostate cancer after taxane-based chemotherapy and novel hormonal therapy failure.
Authors: Chang Gon Kim, Yeo Gyeong Ko, Jongjin Yoon, Chung Lee, Seung-Hoon Beom, Young Deuk Choi, Woong Kyu Han, Won Sik Ham, Hyunho Han, Jongsoo Lee, Ji Eun Heo, Daeseong Kim, Eunsil Baek, Sang Woo Kim, Minsun Jung, Sang Joon Shin
Journal: Journal of Clinical Oncology (2025)

174 Background: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by &gt;50% (PSA50) or &gt;90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range: 3–7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusions: Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC, warranting further investigation. Clinical trial information: NCT06236789 .
Survival disparities by race in advanced urothelial carcinoma (aUC): A real-world analysis.
Authors: Adam Barsouk, Omar Elghawy, Jonathan Henry Sussman, Jessica Xu, Ronac Mamtani, Lin Mei
Journal: Journal of Clinical Oncology (2025)

668 Background: Retrospective population data suggest poorer survival for non-White aUC patients. However, data on survival disparities in the era of immuno- and targeted therapies is limited. Methods: This cohort study used Flatiron Health’s nationwide de-identified electronic health record (EHR)-derived database. 7,244 patients (pts) were identified. Pts who started systemic therapy for aUC from 1/1/2017 to 5/1/2024 and had a recorded race were included. Baseline demographics, including social determinants of health (SDOH) score, performance status (PS), disease characteristics, treatment history, and clinical outcomes were abstracted. Progression free survival (PFS) and overall survival (OS) were compared between Black, White and Asian patients via Kaplan-Meier log-rank analysis and Cox proportional hazards models. Independent sample t-tests and chi-square analyses were used for univariate comparisons. P-values &lt; 0.05 were considered statistically significant. Results: A total of 2,388 pts with aUC were identified, with 1.4% Asian, 5.2% Black, 14.4% “other,” and 78.9% White. In 1L, 17.9% received immunotherapy (IO) monotherapy, 4.2% received enfortumab vedotin + pembrolizumab (EVP), 37.5% received carboplatin-based regimens (carbo), 27.8% cisplatin-based regimens (cis), and 12.5% other chemotherapy (p=0.317). ECOG PS&gt;1 at diagnosis was associated with non-White race (p=0.022). Black patients received treatment at an academic center (41.0%) more often than White patients (25.6%; p&lt;0.001). Black pts had lower SDOH score compared White (p&lt;0.001). Asian (HR0.73, p=0.3) and Black (HR1.07, p=0.3) pts had similar PFS to White pts, as well as similar OS with HR0.85(p=0.4) and HR1.05(p=0.4), respectively. On Cox univariate analysis, there was no significant 1L PFS difference between White, Asian, and Black pts on cis (n=665, p=0.3), carbo (n=895, p=0.7), EVP (n= 25, p=0.8), or IO (n=428, p=0.3). OS was not significantly different by race for any 1L therapy. Conclusions: In a large real-world database, race did not affect overall aUC survival. Baseline characteristics and survival by race. Black (n=124) White (n=1884) Asian (n=33) Other (n=344) Sig (p) Baseline Characteristics ECOG PS 0-1 (%) 55.5 64.6 58.2 62.1 0.027 2-4 (%) 18.5 15.5 19.4 15.2 Academic treatment center (%) 36.6 25.9 13.4 13.2 &lt;0.001 Mean SDOH score (0-5) 2.27 3.26 3.38 2.97 &lt;0.001 1L Treatment IO (%) 23.8 16.4 20.0 17.5 0.317 EVP (%) 5.7 3.9 4.4 4.0 Carbo (%) 32.9 36.5 37.4 38.0 Cis (%) 27.4 29.2 27.8 29.8 Other (%) 10.2 14.0 10.4 10.7 Survival 1L mPFS (m) 5.2 4.6 5.1 4.2 0.300 mOS (m) 5.3 6.9 8.7 5.2 0.400 Sig values (p&lt;0.05) in bold.
Evaluation of systemic therapy and surgical consolidation in patients with node positive upper tract urothelial carcinoma.
Authors: Joon Kyung Kim, Katelyn Spencer, Will Cranford, Justus Fleisch, Zin Myint, Derek B. Allison, Frances Marian Martin, Stephen Strup, Christopher McLouth, Patrick J. Hensley
Journal: Journal of Clinical Oncology (2025)

816 Background: The recommended treatment for high-grade upper tract urothelial carcinoma (UTUC) includes radical nephroureterectomy with regional lymph node dissection for clinically organ-confined disease. The timing of peri-operative systemic therapy is multifactorial, with extrapolation of data from muscle-invasive bladder cancer in the neoadjuvant setting, and level 1 data for UTUC in the adjuvant setting. The timing of peri-operative systemic therapy and need for surgical consolidation in the clinically node positive setting is even more unclear. The goal of this study is to compare survival in cN+ patients managed with neoadjuvant, adjuvant, and systemic therapy alone approaches. Methods: Patients with cT0-4 N1-3 M0 UTUC who received chemotherapy with or without nephroureterectomy (NU) between 2018 and 2021 in the National Cancer Database (NCDB) were included. Patients were stratified into three treatment groups: chemotherapy only (CO), neoadjuvant chemotherapy followed by nephroureterectomy (NAC-NU), and nephroureterectomy followed by adjuvant chemotherapy (NU-AC). OS was analyzed using Kaplan-Meier analysis and log rank tests. Cox proportional hazard models were employed to adjust for potential confounders. Results: A total of 1193 patients were included (CO, NAC-NU, and NU-AC treatment groups consisted of 495, 287, and 411 patients, respectively). Patients in the CO group were older (P&lt;0.001), more commonly males (P&lt;0.001) compared with NAC-NU and NU-AC cohorts. There was no significant difference in Charlson comorbidity index between the three groups. The pathologic complete response rate (ypT0N0) in the NAC-NU was 6.5%. Patients managed with NAC-NU exhibited the most favorable OS compared to NU-AC and CO (P&lt;0.0001), with 3-year OS 65.4% (95% CI 58.4%-73.3%), 53.5% (47.9%-59.6%), and 20.8% (15.7%-27.6%) in these groups, respectively. On multivariate analysis controlling for age, sex, and clinical stage using NAC-NU as a referent, NU-AC and CO exhibited inferior OS (HR 1.48, 95% CI 1.06-2.06, P=0.021 and HR 2.92, 2.14-4.00, P&lt;0.001, respectively). Conclusions: The use of neoadjuvant chemotherapy followed by nephroureterectomy provides optimal survival outcomes in patients with cN+ high-grade UTUC. These data suggest that, when feasible, surgical consolidation is an important treatment component in patients with cN+ disease, likely owing to low rates of pathologic complete response. Estimated overall survival at 1- and 3-year endpoints. Treatment Sample Size 1 Year Survival (95% CI) 3 Year Survival (95% CI) Chemo Alone 348 57.6% (52.5% - 63.2%) 20.8% (15.7% - 27.6%) Chemo before Surgery 202 80.8% (75.4% - 86.6%) 65.4% (58.4% - 73.3%) Surgery before Chemo 329 72.8% (68.1% - 77.8%) 53.5% (47.9% - 59.6
Neoadjuvant androgen deprivation therapy with enzalutamide plus the glucocorticoid receptor modulator relacorilant versus placebo for patients with high-risk localized prostate cancer.
Authors: Mohammad O. Atiq, Walter Michael Stadler, Ashley Page, Meghan Catenacci, Akash Patnaik, Gladell P Paner, Scott Eggener, Russell Zelig Szmulewitz
Journal: Journal of Clinical Oncology (2025)

TPS436 Background: Despite definitive local treatment, high risk localized prostate cancer (PC) patients (pts) have a 36-46% risk of biochemical recurrence (1). Neoadjuvant (NAJ) treatment with androgen receptor signaling inhibition (ARSI) improves pathologic outcome at the time of prostatectomy (2), and 3-year biochemical recurrence-free survival (bRFS) was strongly tied to pathologic complete response (pCR) plus minimal residual disease (MRD). One way to improve on this strategy is to target potential mechanisms of resistance to ARSI. A study of localized high-risk prostate cancer treated with NAJ ARSI plus androgen deprivation therapy (ADT) showed enrichment of glucocorticoid receptor (GR) expression in residual tumors (3). Inhibiting GR signaling decreases resistance to the ARSI enzalutamide (4). We previously demonstrated the safety of the combination of the selective GR modulator (SGRM) relacorilant plus enzalutamide (5). We have thus designed a study evaluating the efficacy of this combination given neoadjuvantly. Methods: This phase 2 study is a placebo-controlled randomized trial of 6 months of NAJ ADT and enzalutamide plus relacorilant/placebo (2:1). The primary objective of this study is response, measured by pCR and MRD at radical prostatectomy (RP). Eligible patients include those with localized histologically confirmed prostatic adenocarcinoma classified as high risk or very high-risk per NCCN guidelines. Enlarged lymph nodes below the iliac bifurcation are allowed. Following randomization pts will be treated with LHRH agonist plus enzalutamide with or without relacoriliant and undergo RP 1 month later. The total sample size is 90 patients with an interim analysis for futility conducted after 45 pts undergo RP. A chi-square test will be used to compare the proportion of patients achieving pCR/MRD. Assuming a true CR/MRD rate of 15% in the control group, 90 patients total would yield a power of 80% with a hypothesized CR/MRD of 32% in the relacorilant group, based on a one-sided test at the alpha=0.15 significance level. As secondary endpoints, we will evaluate radiographic response within the prostate with multiparametric MRI (mpMRI) imaging and the 3-year bRFS and MFS rates in both arms. Exploratory endpoints include demonstrating correlation between enhanced mpMRI imaging and pathologic response, as well showing decreased nuclear hormone receptor-driven proliferative gene expression in viable PC due to combined NAJ GR antagonism and ARSI compared to ARSI alone. The study is currently open and is seeking additional sites. 1. Falgario U, JAMA Netw Open 2023. 2. McKay R, J Urol 2021. 3. Efstathiou E, Eur Urol 2019. 4. Isikbay M, Horm Cancer 2014. 5. Desai, CCR , 2024. Clinical trial information: NCT05726292 .
Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based on line of therapy.
Authors: Nicolas Sayegh, Yeonjung Jo, Zeynep Irem Ozay, Chadi Hage Chehade, Georges Gebrael, Micah Ostrowski, Patrick Campbell, Nishita Tripathi, Siqi HU, Beverly Chigarira, Ethan Anderson, Richard Ji, Gliceida Galarza Fortuna, Vinay Mathew Thomas, Haoran Li, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami
Journal: Journal of Clinical Oncology (2025)

82 Background: Lu is a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical that delivers beta radiation to PSMA-positive cells. It is approved for pts with mCRPC who had prior progression on an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy. However, there are limited real-world data on the efficacy of Lu based on the line of therapy. Herein, we aimed to assess the survival outcomes of pts with mCRPC receiving Lu in a real-world setting. Methods: This retrospective study utilized the nationwide Flatiron Health electronic health record (EHR) derived de-identified database. Eligibility: pts diagnosed with mCRPC who received Lu for the first time. Survival was calculated from the date pts received their first treatment with Lu. Time to next treatment (TTNT) and overall survival (OS) were summarized using Kaplan Meier survival estimates and its 95% confidence intervals (CI). Results: Of the overall cohort of 24,105 pts with metastatic prostate cancer in the dataset, 303 diagnosed between 1/1/2013 and 7/11/2023 received treatment with Lu. The median age of these pts was 75 years (IQR 69 – 80). The majority were White non-Hispanic (69%), treated in a community practice (82%), covered by a commercial health plan (86%), and received Lu in the third line or later (91.4%). For pts treated with Lu, the median TTNT was 8.5 months (95% CI, 7.3 – 9.8), and the median OS was 12 months (95% CI, 11 – 15). Median TTNT and OS by line of therapy are summarized (Table). Conclusions: Lu retains clinical activity in pts with mCRPC regardless of line of therapy. These data may aid with patient counseling, prognostication, and selection of therapy in the clinic. Median TTNT and OS by line of therapy in pts with mCRPC receiving Lu. Line of therapy Number of pts, n (%) Median TTNT (mo) (95% CI) Median OS (mo) (95% CI) 2 26 (8.6) 8.5 (5.6, -) 12 (8.5, -) 3 77 (25.4) 8.0 (6.4, 11) 17 (8.9, -) 4 82 (27) 8.2 (6, 10) 10 (7.2, 22) 5 64 (21) 9.8 (6, 13) 13 (11, -) 6 28 (9.2) 9 (5.7, -) 13 (12, -) 7 17 (5.6) 10 (7.3, -) 10 (7.3, -) 8 6 (2) 7 (3.7, -) (3.7, -) 9 2 (0.7) 7.3 (3, -) 10 (8.6, -) 14 1 (0.3) 8.6 (-, -) 14 (-, -)
Modified transurethral resection of bladder tumors: A comparison study of chemotherapy-enhanced endoscopic submucosal en bloc dissection versus conventional resection.
Authors: Xi Liu, Yiding Wang, Zhe Wang, Bo Shao, Qiang Liu, Changqi Li, Chengcheng Lv, Huan Bi, Guangyi Shan, Ang Chen, Yu Zeng
Journal: Journal of Clinical Oncology (2025)

721 Background: High recurrence rates plague patients with nonmuscle invasive bladder cancer (NMIBC) following transurethral resection of bladder tumors (TURBT). In response, we have developed a modified TURBT procedure that integrates en bloc resection, endoscopic submucosal dissection, and the injection of chemotherapeutic drugs into the submucosa (cESD-TURBT).This study aims to determine if cESD-TURBT yields better outcomes than conventional TURBT (cTURBT). Methods: This retrospective observational study was conducted on patients diagnosed with cTa–T1 bladder cancer who received TURBT between December 2020 and July 2023 in Liaoning Cancer Hospital. Participants were grouped based on the type of treatment they received: cESD-TURBT (n=118) or conventional TURBT (cTURBT, n=105). Hydroxycamptothecin was the chemotherapeutic agent used for submucosal injections. The primary outcome was recurrence-free survival (RFS) of the treated bladder cancer. Secondary outcomes included disease recurrence within one year, operation duration, length of postoperative hospitalization, and complication rates. Statistical analyses were performed using appropriate tests, with a threshold of P &lt; 0.05 defined as statistically significant. Results: Among the 223 patients, cESD-TURBT cohort demonstrated enhanced RFS compared to cTURBT cohort, with a median follow-up of 775 days (IQR 414-1040). The recurrence rate in the cESD-TURBT cohort was 18.64% (22/118), against 39.05% (41/105) in the cTURBT cohort, with a log-rank hazard ratio of 0.49 (95% CI 0.29-0.82; p=0.0053). Furthermore, cESD-TURBT registered fewer postoperative complications than cTURBT, markedly reducing occurrences such as the obturator reflex (2% vs. 9%). The difference in operation times was not statistically significant, with cESD-TURBT averaging 49.0 ± 21.0 minutes and cTURBT 44.3 ± 23.8 minutes, the difference being statistically negligible (p=0.127). Conclusions: For patients with NMIBC, cESD-TURBT significantly lowers recurrence rates compared to cTURBT and is associated with fewer postoperative complications. Our study reveals that the chemotherapy-enhanced ESD-TURBT technique significantly improves recurrence-free survival and reduces complications, making it a superior method over conventional TURBT for bladder tumor removal.
Phase 1 dose escalation (DEs) &amp; expansion (DEx) study to evaluate the safety &amp; efficacy of IDE397 plus sacituzumab-govitecan in patients with advanced urothelial carcinoma (UC) with MTAP deletion (MTAPdel).
Authors: Charlene Mantia, Chang Gon Kim, Jordi Rodon Ahnert, Omar Alhalabi, Alexander Z Wei, Mark N. Stein, Melissa Lynne Johnson, Benjamin Garmezy, Alok Tewari, Sid Devarakonda, Abhishek Tripathi, Benedito A. Carneiro, Inkeun Park, Valentina Boni, Emily Liu, Jasgit C. Sachdev, Mick O'Quigley, Michael White, Darrin M. Beaupre, Hye Ryun Kim
Journal: Journal of Clinical Oncology (2025)