tbuckley/cabot-search huggingface dataset:
Long-term safety outcomes of <sup>177</sup> Lu-PSMA-617 in patients with prostate cancer.
Authors: Alton Oliver Sartor, Shilpa Gupta, Alicia K. Morgans, Luke Nordquist, Michael Crosby, Jeff M. Michalski, Fred Saad, Neal D. Shore, Hyun Kim, Natalie Carnahan, Shaheen Alanee, Arijana Jobst, Sanjay Samantray, Diego Ospina Gonzalez, Ken Herrmann
Journal: Journal of Clinical Oncology (2025)

TPS294 Background: Approval of [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy, was based on the results of the Phase 3 VISION study (NCT03511664). It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related risks. To this end, the long-term follow-up (LTFU) safety study (NCT05803941) has been established. Findings from the LTFU study will be crucial for assessing delayed toxicities for patients with PSMA-positive metastatic prostate cancer treated with 177 Lu-PSMA-617 globally. Methods: The LTFU study is a prospective, multi-center, non-EU post-authorization safety study. Patients who received ≥1 dose of 177 Lu-PSMA-617 within one of the prospective parent studies (Table 1) are eligible. Patients may enroll in the LTFU study after fulfilling the requirements of their corresponding parent study. The primary endpoint is the number and proportion of selected adverse events (AEs), including myelosuppression, xerostomia, renal failure, xerophthalmia, and second primary malignancies (eg, myelodysplastic syndrome or acute myeloid leukemia), other serious AEs, and changes in laboratory values. The secondary endpoint is the number and proportion of deaths. Following enrollment, patients will undergo assessments at baseline, and then every 6–8 months for up to 10 years after their first dose of 177 Lu-PSMA-617 or until death. At each visit, a review of selected treatment-related AEs (xerostomia, xerophthalmia, myelosuppression), any-cause AEs (renal toxicity, new diagnoses of second primary malignancies), and treatment-related serious AEs will be conducted. Physical and laboratory assessments, as well as details on concomitant medications and interventions, including anti-cancer therapies, will be collected. Patients may receive treatment with any medical intervention. Interim analyses are planned at 2 and 5 years post-study activation. Enrollment is ongoing (n=13). Clinical trial information: NCT05803941 . Parent studies of the long-term follow-up safety study. Trial Indication Phase N (all groups) ClinicalTrials.gov ID VISION (+sub-study) Post-taxane mCRPC 3 831 (+30) NCT03511664 PSMAfore Pre-taxane mCRPC 3 469 NCT04689828 PSMAddition mHSPC 3 1144 NCT04720157 177 Lu-PSMA-617 in patients with moderately or severely impaired, or normal renal function Post-taxane mCRPC 2 20 a NCT06004661 a Planned. mCRPC, metastatic castration-resistant prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer.
CLARIFY: Positron emission tomography using <sup>64</sup> Cu-SAR-bisPSMA in patients with high-risk prostate cancer prior to radical prostatectomy—A phase 3 diagnostic performance study.
Authors: Michael A. Gorin, Eva Lengyelova, Luke Nordquist, Glynn Morrish, Othon Gervasio, Robert M. Miller, Neal D. Shore
Journal: Journal of Clinical Oncology (2025)

TPS429 Background: Prostate cancer (PC) is the second most prevalent cancer in men globally. In men with newly diagnosed, high-risk disease, PC most often spreads to the pelvic lymph nodes (LNs) before becoming widely metastatic. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is strongly overexpressed in PC, making it an ideal target for imaging and therapy. 64 Cu-SAR-bisPSMA may offer several advantages over the currently approved PSMA positron emission tomography (PET) agents due to its bivalent structure (SAR-bisPSMA) and longer half-life of 64 Cu (12.7h vs. &lt;2h for 18 F and 68 Ga). 64 Cu-SAR-bisPSMA has demonstrated higher tumor uptake (2-3x), prolonged retention and detection of additional PC lesions compared to approved PSMA agents. This Phase 3 diagnostic trial aims to establish the diagnostic performance of 64 Cu-SAR-bisPSMA PET to detect regional nodal metastases in men with high-risk PC. Methods: CLARIFY (NCT06056830) is a multi-center, single-arm, non-randomized, open-label Phase 3 diagnostic study of 64 Cu-SAR-bisPSMA. The target population is patients with untreated, histopathology-confirmed PC with high-risk features, who are proceeding to radical prostatectomy (RP) with pelvic lymph node dissection (PLND). The primary endpoint is to assess the sensitivity and specificity of 64 Cu-SAR-bisPSMA PET to detect pelvic nodal metastases. Secondary objectives include assessment of safety and determining the positive and negative predictive value of 64 Cu-SAR-bisPSMA PET. A total of 383 patients will be enrolled. Standard of care (SOC) imaging will be acquired at screening (e.g. computed tomography [CT], approved PSMA PET/CT). Eligible patients will receive a single administration of 64 Cu-SAR-bisPSMA (200 MBq) followed by a PET/CT scan on Day 1 (1-4h post-dose, same-day imaging) and on Day 2 (24±6h post-dose, next-day imaging). Patients will then proceed to RP with PLND. The specimens from surgery will be processed and analyzed locally to derive the Standard of Truth (SOT). The 64 Cu-SAR-bisPSMA PET/CT scans will be interpreted locally and by 3 independent, blinded, central readers. Each reader will assess the scans for the presence of abnormal 64 Cu-SAR-bisPSMA uptake in the pelvic LNs, prostate gland, extra-pelvic LNs, visceral/soft tissue and bone. The diagnostic performance of 64 Cu-SAR-bisPSMA will be based on the PET result on the respective day independently (Day 1 and 2) matched against the SOT. The study is open for recruitment in sites in the United States and in Australia. Clinical trial information: NCT06056830 .
Impact of adding immunotherapy to chemotherapy for metastatic neuroendocrine bladder cancer in the National Cancer Database.
Authors: Lingbin Meng, Peng Wang, Shihua Wang, Yuanquan Yang, Feng Hong, Katharine A. Collier, Elshad Hasanov, Shang-Jui Wang, Debasish Sundi, Akshay Sood, Danielle Elise Zimmerman, Fuat Bicer Bicer, Timothy D. Gauntner, Edmund Folefac, Paul Monk, Amir Mortazavi, Steven K. Clinton
Journal: Journal of Clinical Oncology (2025)

748 Background: Metastatic neuroendocrine bladder cancer is a rare and aggressive malignancy characterized by poor prognosis and limited effective treatment options. Standard chemotherapy has shown limited success, necessitating novel therapies. We hypothesized that adding immunotherapy to chemotherapy would improve overall survival (OS) in these patients. Methods: We conducted a retrospective cohort study of 1,410 patients diagnosed with metastatic neuroendocrine bladder cancer between 2004 and 2020 using the National Cancer Database (NCDB). Treatment groups included no treatment, chemotherapy alone, and combined immunochemotherapy. Survival outcomes were analyzed using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression models, adjusting for age, tumor size, Charlson-Deyo comorbidity score, and residential area. Results: Median OS was 1.8 months (95% CI: 1.6-2.0) for patients receiving no treatment (n=460), 9.6 months (95% CI: 8.9-10.1) for chemotherapy alone (n=860), and 11.7 months (95% CI: 9.6-14.8) for combined immunochemotherapy (n=90) (P &lt; 0.001 for immunochemotherapy vs. both other groups). Further analysis revealed that first-line immunotherapy initiated within 30 days of chemotherapy (n=21) significantly improved OS (median 11.6 months; 95% CI: 6.8–16.1; P=0.0374) compared to chemotherapy alone. Notably, immunotherapy initiated after 30 days (n=69, median OS 12.4 months; 95% CI: 9.0–14.8; P=0.0264), whether as first-line or second-line therapy, also showed superior efficacy to chemotherapy alone. These findings suggest that if first-line immunotherapy is not administered, subsequent immunotherapy should still be considered. Multivariable Cox regression analysis showed that immunochemotherapy compared to chemotherapy alone was associated with a lower hazard for death (HR = 0.80; 95% CI: 0.66-0.97; P = 0.0242), while patients receiving no treatment had an increased risk of death (HR = 3.50; 95% CI: 3.00-3.90; P &lt; 0.0001). Additional factors associated with increased mortality included older age, larger tumor size, and higher Charlson-Deyo score. Conclusions: Adding immunotherapy to chemotherapy significantly improved OS in metastatic neuroendocrine bladder cancer. First-line immunochemotherapy showed substantial benefits, but late initiation also improved outcomes. These findings support incorporating immunotherapy into first-line protocols and consider it for subsequent lines. Prospective clinical trials are needed to optimize immunotherapeutic strategies for this aggressive malignancy.
Efficacy of neoadjuvant/induction (NAC) chemotherapy in nonmetastatic muscle-invasive bladder cancer treated with chemoradiotherapy (CRT): A systematic review and meta-analysis.
Authors: Mariana Fauth Seibel, Letícia Dal Ri, Bruno Souza, Julia Belone Lopes, Vitor Teixeira Liutti, Daniel Vilarim Araujo
Journal: Journal of Clinical Oncology (2025)

814 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the established standard for nonmetastatic muscle-invasive bladder cancer (MIBC). However, bladder-sparing approaches using chemoradiotherapy (CRT) offer comparable outcomes. While NAC has proven beneficial before RC, its value prior to CRT remains uncertain. This systematic review and meta-analysis aimed to evaluate the impact of NAC on outcomes in patients undergoing CRT for bladder preservation. Methods: A comprehensive search of PubMed, Embase, and Cochrane databases was conducted to identify studies comparing NAC plus CRT versus CRT alone in MIBC. Both randomized controlled trials (RCTs) and observational studies were eligible. Studies with overlapping populations or non-English publications were excluded. Heterogeneity was assessed with I² statistics, and all analyses were performed using random-effects models in Review Manager 5.4.1. The study was registered in PROSPERO (CRD42024590258). Results: Four observational studies, encompassing 3,354 patients, were included as no RCTs met the inclusion criteria. NAC was administered to 656 patients (19.5%). Median follow-up ranged from 15.9 to 74.4 months. All patients in the NAC group received platinum-based chemotherapy (MVAC, ddMVAC, GC, or CMV). Concurrent CRT regimens included cisplatin, gemcitabine, or mitomycin with radiotherapy. No significant difference in overall survival was observed between NAC + CRT and CRT alone (HR = 0.99, 95% CI 0.87–1.13, p = 0.89, I² = 0%). Disease-free survival data were available from two studies, showing no significant difference (HR = 1.07, 95% CI 0.57–2.01, p = 0.82, I² = 39%). All included studies had a serious risk of bias, mainly due to confounding and selection bias, as assessed by the ROBINS-I tool. The overall certainty of the evidence was rated as very low using the GRADE framework. Conclusions: Our analysis found no survival benefit from adding NAC to CRT in patients with MIBC. However, the quality of the evidence is very low, largely due to the retrospective nature of the data. Further randomized clinical trials are needed to clarify the role of NAC in bladder preservation strategies.
Clinicopathological variations between early and late recurrence in bladder cancer post-radical cystectomy.
Authors: Josh Ku, Chirag Doshi, Anosh Dadabhoy, Leilei Xia, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2025)

874 Background: Over 50% of patients diagnosed with muscle-invasive bladder cancer are estimated to experience urothelial cell carcinoma (UCC) recurrence following radical cystectomy (RC). Current studies have found clinicopathological factors associated with overall UCC recurrence; however, there is a lack of data on variations between patients with early versus late recurrence. This study examines the clinicopathological differences of these cohorts. Methods: Within our single institutional IRB-approved cystectomy database, we reviewed 1,050 patients from 1971 - 2023 who underwent RC with intent to cure for primary UCC and experienced recurrence at the University of Southern California. Patients included had documented recurrence via biopsy or imaging. Patients with distant metastasis at RC were excluded. Clinicopathological factors were chosen based on significance in prior studies. Early recurrence (ER) was defined as within two years of cystectomy, the most common time frame for UCC, and late recurrence was beyond two years. Cox regression and chi-squared tests were utilized to compare the groups. Results: Among 1,050 patients, the median age was 68. Of the 928 open cystectomies, 73.2% had ER, compared to 87.7% of the 122 robotic cystectomies. ER rates were 71.9% for the 588 orthotopic diversions, 69.9% for the 143 continent diversions, and 82.5% for the 319 incontinent diversions. Factors predictive of ER included older age (OR = 1.582, p = 0.0017), higher Charlson Comorbidity scores (OR = 1.460, p = 0.0112), higher ASA scores (OR = 1.900, p = 0.001), hydronephrosis prior to RC (OR = 1.944, p = &lt;0.0001), lymphovascular invasion (OR = 1.472, p = 0.0383), lymph node involvement at RC (OR = 2.770, p = &lt;0.0001), neoadjuvant chemotherapy (OR = 3.457, p = &lt;0.0001), incontinent urinary diversions (OR = 1.832, p = 0.0008), greater than pT3 pathological staging (p = &lt;0.0001), and variant histology (OR = 1.782, p = 0.0006). Conclusions: This study identifies clinicopathological risk factors significantly associated with ER. By describing these factors, this study aims to improve predictions of UCC recurrence patterns and inform personalized treatment. Further research is needed to validate our findings and optimize surveillance protocols for at risk patients. Multivariate analysis of variables predictive of early recurrence. Variable Hazard ratio p-value Age &gt; 70 1.464 (1.054 - 2.042) 0.0238 Pre-operative Albumin 0.990 (0.981 - 0.999) 0.0227 Neoadjuvant Chemotherapy 3.527 (2.187 - 5.930) &lt;0.0001 Pathological Staging Organ - Confined Extravesical Lymph Node Positive Ref4.511 (2.955 - 7.024)7.553 (5.000 - 11.636) &lt;0.0001 Urinary Diversion Orthotopic Diversion Continent Diversion Incontinent Diversion Ref0.807 (0.513 - 1.281)1.459 (1.003 - 2.139) 0.0531 Adjuvant Chemotherapy 0.568 (0.372 - 0.863) 0.0083
Molecular insights of low-PSA–expressing high-risk prostate cancer.
Authors: Goutam Chakraborty, Nabila Zaman, Adriana M Pedraza, Natasha Kyprianou, Ashutosh K. Tewari
Journal: Journal of Clinical Oncology (2025)

416 Background: Despite advances in molecular genetics and genome sequencing, identifying lethal and non-lethal forms of prostate cancer in the early stages of the disease remains challenging. A significant number of prostate cancer patients have high-risk tumors that produce low levels of prostate-specific antigen (PSA) at the time of diagnosis. There is an indication that the therapeutic outcome of these patients, may be considered unfavorable as they may not respond as well to ADT or androgen receptor pathway inhibitors (ARPI). Consequently, this type of high-risk prostate cancer with low PSA secretion may be associated with a unique subtype of the disease that has not been fully characterized. Methods: From 2013 to 2023, 3,619 patients diagnosed with prostate cancer underwent robotic-assisted radical prostatectomy (RARP) performed by a single experienced surgeon (AKT). The patients were classified into four groups based on their PSA levels: very low (&lt;2.5 ng/ml), low (2.6-5.0 ng/ml), medium (5.1-8.0 ng/ml), and high (&gt;8.0 ng/ml). We conducted an ANOVA analysis to compare various clinical characteristics across these groups. Additionally, we explored the gene expression profiles from the Cancer Genome Atlas (TCGA) prostate cancer cohort, specifically examining differential PSA/KLK3 mRNA expression within cancer cells. Furthermore, we selected and expanded single-cell clones from the LNCaP parental population to investigate the molecular landscape of low PSA expressing prostate tumor cells. Results: We observed that patients with high-risk prostate cancer and a very low PSA level (&lt;2.5 ng/ml) had higher rates of biochemical recurrence compared to those with high-grade cancer but PSA levels (&gt;2.5 ng/ml). Additionally, we noticed a significantly high presence of seminal vesicle (p= 1.058e-05) and neurovascular invasion (p=0.0047) in both the very low and high PSA groups compared to the other two groups. Importantly, the very low PSA group exhibited a higher rate of lymph node invasion (p= 0.00095) compared to the other three groups. Our transcriptomic analysis in the TCGA cohort revealed that genes which are upregulated in the very low PSA group compared to the high PSA group are significantly (p&lt;0.001) enriched in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, our study on LNCaP-derived clones revealed an increased migration potential and elevated expression of mesenchymal markers in LNCaP-PSA Low clones compared to the clones expressing high PSA. Conclusions: Our research identifies a distinct subtype of localized prostate cancer, demonstrating that low-PSA, high-risk prostate cancer is significantly invasive and leads to potentially lethal disease. This highlights the need for further investigation to better understand the biology of this poorly defined but aggressive subtype of localized prostate cancer.
The role of conventional imaging and piflufolastat F18 in newly diagnosed and recurrent prostate cancer patients: Preliminary observations from the PYLARIFY Registry.
Authors: Neal D. Shore, Lorraine O'Donnell, Basil Wilson, Shashank Subhash Dave, Arpit Kashyap, Nicholas Lazarou
Journal: Journal of Clinical Oncology (2025)

41 Background: Next generation imaging modalities for the diagnosis and characterization of prostate cancer have seen increased utilization in the past several years. PSMA-PET imaging has seen particular promise as a more accurate modality compared to conventional (CT, skeletal scintigraphy and PET) imaging. Use of PSMA imaging can significantly improve how prostate cancer is staged and thus enhance the clinicians’ confidence in therapeutic decision making. Methods: The PYLARIFY Registry (NCT 05712473), conducted under SoNaR, a Specialty Networks Registry, is a US-based multi-center prospective 5 year observational study following patients receiving standard of care piflufolastat F18 imaging as part of their prostate cancer management. The registry includes newly diagnosed patients who have not yet initiated any treatment (Cohort 1) and patients with biochemical recurrence (Cohort 2). Demographics, all baseline imaging procedures and the frequency of each type of imaging for the first 100 enrolled patients were analyzed. We also explored time-to-PSMA for newly diagnosed patients who received conventional imaging as part of their staging assessment. The clinician confidence ratings that the piflufolastat F18 imaging had on treatment decision making were also evaluated. Results: The first 100 patients had a mean age of 71.0 (SD 9.1) and 80% had a Gleason Grade group of 2 or higher. At least 1 conventional imaging procedure prior to the piflufolastat F18 PET scan was performed on 10% of patients in Cohort 1 and 77% in Cohort 2. For Cohort 1 patients, piflufolastat F18 scans were preceded by a total of 4 imaging procedures, with an average of 1 conventional imaging procedure per patient prior to their piflufolastat F18 scan. Cohort 2 patients had a total of 95 imaging procedures with an average of 1.58 conventional imaging procedures per patient prior to their piflufolastat F18 scan. The 3 most utilized conventional imaging modalities in both cohorts of patients that received conventional imaging prior to piflufolastat F18 scans were CT (80%), and skeletal scintigraphy (72%) and PET (26%). The median difference in diagnostic journey length between Cohort 1 newly diagnosed patients having conventional imaging and those having only piflufolastat F18 was 28 additional days. Across both cohorts, clinicians rated improvement in treatment planning confidence following 96% of piflufolastat F18 scans. Conclusions: Piflufolastat F18 provides a high degree of confidence for prostate cancer patient management. A growing number of patients are being managed with piflufolastat F18 scans only. Many patients however still undergo lengthy and resource-intensive conventional imaging procedures prior to their piflufolastat F18 scan.
Complications after transurethral resection of bladder tumor: Findings from the 2022 ACS NSQIP database.
Authors: Chirag Doshi, Mazyar Zahir, Domenique Escobar, Leilei Xia, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2025)

742 Background: Transurethral resection of bladder tumor (TURBT) is a widely utilized procedure for the diagnosis and treatment of bladder cancer (BC). Despite its well-established role, TURBT is associated with a relatively high rate of postprocedural complications. This study aimed to provide an update on the most prevalent complications following TURBT, using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) 2022 database. Methods: The ACS NSQIP 2022 database was queried for all patients who underwent TURBT. Current Procedure Terminology (CPT) codes 52234, 52235, and 52240 were used to identify size-specific TURBTs. Standard statistical analysis using R version 4.4.1 was performed to determine complications. Results: A total of 9,448 TURBTs were included in our analysis. Median age was 73 years old (IQR: 58-88), 2,315 females and 7132 males that received a TURBT within the cohort. Patients with concurrent procedures were removed from the final analyses, but those who received intravesical chemotherapy or underwent concurrent ureteroscopy were retained. The overall complication rate of TURBT was 8.04% in 2022. Postprocedural urinary tract infection (UTI) - within 30 days after TURBT - was the most common complication, accounting for 4.5% of total complications. 160 patients or 1.7% were found with more than one complication. There were no significant differences in complications by age or sex (p = 0.129 and p = 0.124); however larger tumors were related to higher likelihood of post-operative complications. Conclusions: Serious adverse complications after TURBT are rare and TURBTs are generally a safe procedure. However, the ACS NSQIP database suggests that postprocedural UTI are the most common but the rate may be marginally higher than previously reported in TURBT patients. The key limitation of this study was the inability to report the most serious complications of TURBT – i.e. bladder perforation and TUR syndrome – due to NSQIP database’s inability to capture detailed case-specific data. More detailed studies assessing patient-reported outcomes may provide a better method to evaluate the types of complications following TURBT. 30-day complications after TURBT in 2022. 30-day Complications Frequency Percentage Acute Renal Failure 4 0.043% Cardiac Arrest Requiring CPR 10 0.108% Still in Hospital after 30 days 15 0.161% Stroke/CVA 22 0.237% Pneumonia 31 0.333% DVT/PE/Thrombophlebitis 48 0.508% Transfusions Required 122 1.312% Progressive Renal Insufficiency 135 1.452% Related Reoperations within 30 days 148 1.592% Urinary Tract infections 430 4.603% Total 760 8.044%