bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognosis for patients with bladder cancer with recurrence after pathologic complete response or pathologic downstaging after radical cystectomy: EUMC RC cohort study.
Authors: Jo Jungmin , Lee Dong-Hyeon 
Published: June 2024

e16613 Background: Pathologic complete response (pCR, pT0N0M0) or pathologic downstaging (pDS, <pT2N0M0) for bladder cancer is associated with increased overall survival (OS). However, some patients who achieved pCR or pDS experience recurrence, but these patients have not been targeted for adjuvant immunotherapy in studies to date, and the prognosis has not been well studied. We aim to examine the prognosis for bladder cancer patients with recurrence after pCR or pDS after radical cystectomy (RC). Methods: Of the 1562 patients who underwent a RC for bladder cancer between June 1996 and November 2023, 712 (45.6%), including 29 patients who did not undergo lymph node dissection, were identified as having pCR or pDS on final pathology. Of the 712 patients, 108 (15.2%) experienced recurrence. Results: Among 712 patients, 170 (23.9%) achieved pCR, 305 (42.8%) in pT1, 140 (19.7%) in Tis, and 97 (13.6%) in Ta. Out of the 170 patients with pCR, 12 (7.1%) experienced recurrence. Among the 305 patients with pT1, recurrence occurred in 63 (20.7%), and out of the 140 patients with Tis and 97 with Ta, 24 (17.1%) and 9 (9.3%) had recurrence, respectively. Only 150 (21.1%) patients received neoadjuvant chemotherapy (NAC), and 30 (27.8%) of the 108 patients who relapsed had received NAC. The median age of 108 patients with recurrence was 66.8 years old (range 31.3–86.2), and variant histology was observed in 10 (9.3%) surgical specimens. At a median follow-up of 36.7 months, the median time to recurrence was 15.5 months (10.4–20.6). Sixty-seven patients (62%) had local recurrence or lymph node-only metastasis. The distant metastasis was most common in the lung, liver, and bone (42, 38%). Conclusions: Patients with pCR or pDS at the time of radical cystectomy should prudently undergo surveillance, as recurrence and metastasis can still develop. Future studies are needed to reinforce these findings and decide whether to receive adjuvant treatment in the post-NAC setting.
Clinical and pathological characteristics of cancer of unknown primary with renal profile using gene expression profiling (GEP)–based cancer classification.
Authors: Allam Joelle , Ma Li , Zhao Jianping , Estrella Jeannelyn , Higbie Victoria , Willett Anneleis , Matamoros Aurelio , Lano Elizabeth A , Treuner Kai , Raghav Kanwal Pratap Singh , Huey Ryan W 
Published: June 2024

e16627 Background: Cancers of unknown primary (CUP) are rare and heterogeneous tumors with clinically unidentifiable origin at time of diagnosis, accounting for approximately 1-3% of all malignant neoplasms. CUP with Renal Profile (CUP-RP) appears to be a clinically distinct subset, based on immunophenotyping, specifically PAX8 staining. Precision in diagnosis is critical, as cytotoxic chemotherapy options for CUP do not overlap with tyrosine kinase inhibitors or checkpoint inhibitors used for renal cell carcinoma. Gene expression-based cancer classification in patients with CUP offers an objective molecular assessment in the search for CUP origin and further categorization. Methods: We retrospectively evaluated 300 patients with CUP composed of cases classified as renal profile (N=100, clear cell or papillary) or controls (N=200, non-renal cases) using the 92-gene assay (CancerTYPE ID), a validated classifier for predicting tissue of origin, between January 2018 and December 2022. Clinicopathologic data including immunohistochemistry (IHC) and molecular profiling (NeoTYPE) results were collected using pathology specimens and reports. Results: At baseline, median age at diagnosis was 69 years (range 31-89). Most patients were male (63%). For CUP-RP patients, pathology was reported as poorly differentiated in 47% of tumors. Tumors were described as adenocarcinoma in 27%, carcinoma in 63%, and malignant neoplasm in 10%. Median number of IHC stains performed was 11 (range 0-33). PAX8 staining was found to be strongly or focally positive in 88%. PAX8 was not tested in 36% of cases. Compared to non-renal profile CUP, CUP-RP patients were more likely to have bone biopsies (28% vs 16.5%, OR 1.97, p=0.02). CUP-RP were much less likely to have high-TMB (2% vs 28.2%, OR 0.07, p=.001). CUP-RP had a lower proportion of TP53 mutations (18.8% vs 81.2%, OR 0.028, p<0.0001) and KRAS mutations (13.3% vs 86.7%, OR 0.045, p<0.0001). Detailed IHC from 30 CUP-RP cases is shown in the table. CA IX was tested in 2/30 (6.7%) of cases. Conclusions: In this cohort of CUP with a molecular classification of renal cell carcinoma, we found a wide range in diagnostic work-up. The 92-gene assay can serve as an adjunct to IHC, to improve diagnostic accuracy for CUP. Critical immune stains necessary in diagnosis are performed infrequently. While PAX8 was often positive in CUP-RP, it was omitted in over 1/3 of cases. CUP-RP cases had lower TMB and less often mutations in TP53 and KRAS. Gene expression profiling presents an opportunity to complement standard pathology in the workup of this subset of CUP to guide treatment selection and improve clinical outcomes. [Table: see text]
Feasability of single-port gasless retroperitoneal laparoscopic adrenalectomy for patients with adrenal tumor: A prospective control study.
Authors: Liu Zhenhua , He Xiaobo , Long Yuhui , Ma Nan , Lai Renchun , Guo Shengjie 
Published: June 2024

e16628 Background: The safety and efficacy of single-port-gasless retroperitoneal laparoscopic adrenalectomy (SPG-RLA) in the treatment of adrenal tumors have not been fully explored. We aimed to explore the safety and efficacy of SPG-RLA for adrenal tumors. Methods: Thirty patients with adrenal tumors <4 cm undergoing SPG-RLA were prospectively enrolled from July 2022 to February 2023. Operative time, blood loss, conversion and complication rates, and postoperative data were compared to another 30 patients with the same characteristics treated with traditional single-port retroperitoneal laparoscopic adrenalectomy (RP-LESS-A). Results: Both 30 SPG-RLA operations and 30 RP-LESS-A operations were completed without any mortality, reoperation, blood transfusion, or conversion. The mean operative time and blood loss were 62.3 min and 94.1 ml, respectively. Compared with the traditional surgery group, SPG-RLA patients had 15% lower hospitalization costs ( p < 0.001), lowerΔpCO2 (2.52 mmHg vs 6.86 mmHg, p = 0.001) and ΔpH (−0.05 vs −0.08, p = 0.004) values, and similar operative and postoperative complications, the average time to first oral intake (21.2 h vs 19.7 h, p = 0.106), ventilation time ( p = 0.058), duration of drainage ( p = 0.568), postoperative narcotic use ( p = 0.958), and postoperative hospitalization ( p = 0.116). However, the SPG-RLA group had longer operative time (62.3 min vs 45.7 min, p < 0.001), more blood loss ( p = 0.032), and longer incisional length ( p < 0.001). No local tumor recurrence or hormonal relapse was observed in the 6-month follow-up. Conclusions: SPG-RLA is a safe, minimally invasive, and economically viable surgery, which may especially be suitable for low-resource regions and in patients with cardiopulmonary insufficiency due to adrenal tumors. Clinical trial information: ChiCTR220005735 . [Table: see text]
Efficacy and toxicity of [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer in a real-world setting: Results from the U.S. Expanded Access Program and comparisons with phase 3 VISION data.
Authors: Calais Jeremie , Murthy Vishnu , Voter Andrew , Nguyen Kathleen , Allen-Auerbach Martin S. , Caputo Sydney , Ledet Elisa M. , Akerele Opeoluwa , Moradi Tuchayi Abuzar , Lawhn Heath Courtney , Carducci Michael Anthony , Pomper Martin , Paller Channing Judith , Czernin Johannes , Solnes Lilja , Hope Thomas A. , Sartor Oliver , Gafita Andrei 
Published: June 2024

e17061 Background: ThePhase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged overall survival (OS) in metastatic-castration resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSi). The expanded access program (EAP) (NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. The VISION trial required strict inclusion and exclusion criteria, which may not represent the patient population encountered in clinical practice. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 in a real-world setting within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP between May 2021 and March 2022 at four institutions in the United States with available toxicity and outcome data were included. Outcome measures included overall survival (OS), ≥50% PSA decline rates (PSA-RR), and incidences of toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Differences in baseline characteristics, toxicity, and PSA-RR between the EAP and VISION were evaluated using a t-test of proportions. Results: 117 patients with mCRPC were eligible and included. Patients enrolled in the EAP were similarly pretreated with taxane-based chemotherapy regimens (>1 taxane: 47% vs 40%; p=0.16) and more heavily pretreated with ARSi (>1 ARSi: 70% vs 46%; p<0.001). EAP patients had similar levels of ≥3 grade anemia (18% vs 13%; p=0.15), thrombocytopenia (13% vs 8%; p=0.13), and neutropenia (3% vs 3%; p=0.85) and higher levels of ≥3 grade lymphopenia (34% vs 8%; p<0.001). Patients treated within the EAP experienced numerically shorter OS (median OS: 13.7 vs 15.3 months) and similar PSA-RR (40% vs 46%; p=0.29). Median follow-up was numerically shorter in the EAP compared with VISION (14.7 mo vs 20.3 mo). Conclusions: mCRPC patients treated with [177Lu]Lu-PSMA-617 in a real-world setting were more heavily pretreated with ARSi, had a similar safety profile, and experienced numerically shorter OS and similar PSA-RR compared with VISION trial patients. A major limitation of this study is that we did not have access to individual patient data from the VISION trial, so we were not able to assess whether differences in OS between VISION and the EAP were statistically significant.
Examining laboratory-based VISION eligibility and 177Lu-PSMA-617 outcomes in patients with metastatic castration-resistant prostate cancer.
Authors: Ghodsi Alireza , Demirci Ridvan Arda , Gulati Roman , Raychaudhuri Ruben , Cheng Heather H. , Hawley Jessica E. , Yezefski Todd , Haffner Michael C. , Montgomery Robert Bruce , Nelson Peter , Schweizer Michael Thomas , Yu Evan Y. , Chen Delphine L. , Iravani Amir 
Published: June 2024

e17062 Background: Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA-617) is an FDA-approved therapy for metastatic castration-resistant prostate cancer (mCRPC) and commonly used in late-line treatment for patients with extensive disease and diminished organ function. It is unclear whether patients with low bone marrow reserve derive benefit from the treatment. The study aimed to evaluate outcomes of treating mCRPC patients with 177Lu-PSMA-617, classifying them as either VISION-Eligible (VISION-E) or VISION-Ineligible (VISION-I) based on baseline laboratory test results. Methods: This retrospective cohort study evaluated patients who had received at least one cycle of 177Lu-PSMA-617 between June 2022 and July 2023. Eligible patients were then classified as VISION-E or VISION-I using VISION trial eligibility criteria: white blood cell (WBC) count ≥2.5 × 109/L or absolute neutrophil count ≥1.5 × 109/L, platelets (PLT) ≥100 × 109/L, hemoglobin (Hb) ≥9 g/dL, total bilirubin ≤1.5 × upper limit of normal (ULN), ALT or AST ≤3.0 × ULN, serum creatinine ≤1.5 × ULN, and albumin >3.0 g/dL. PSA decline of at least 50% relative to baseline (PSA50), PSA-progression-free survival (PSA-PFS), and overall survival (OS), were evaluated using tests of proportions or Cox regressions. Results: In our study of 123 patients (median age: 73 years, median cycles: 4), 85.4% had ECOG 0 or 1. 75.6% of the cohort were VISION-E, while 24.4% were VISION-I. No substantial differences were observed in baseline characteristics between the two groups, including age (p-value: 0.7) and ECOG (p-value: 0.5). Among VISION-I patients, 73.3% did not meet the threshold for hematologic lab results (16 patients with low Hb, 5 with low PLT, and 4 with low WBC), while 13.3% did not meet criteria for renal lab tests and an additional 13.3% did not meet criteria for liver lab tests. Overall, 52% of patients showed a PSA50, and the median PSA-PFS and OS of the total patient cohort were 9 (95% CI: 7.8-10.2) months and 11 (95% CI: 9.9-12.1) months, respectively. No statistically significant differences in PSA50 were observed between VISION-E (55.9%, 95% CI: 45%-66%) and VISION-I patients (40%, 95% CI: 23%-59%) (p: 0.13). The PSA-PFS and OS were not statistically significant different between VISION-E and VISION-I groups (median OS not reached vs. 13 months, p: 0.4, and median PSA-PFS of 4 months vs. 5 months, p: 0.5) (Table). Conclusions: In this study, the patients who did not meet VISION laboratory thresholds did not have statistically significant different PSA50, PSA-PFS and OS compared to those who met the criteria. A more lenient laboratory threshold appears to be acceptable for treatment with 177Lu-PSMA-617. [Table: see text]
Evaluation of tumor gene expression profile and Gleason score in patients with metastatic prostate cancer.
Authors: Freitas Carla Simone Moreira , Silva Thais Almeida Marques da , Silva Fabiana Rocha , Soares Aleida Nazareth 
Published: June 2024

e17065 Background: The Gleason Score (GS) is a fundamental prognostic indicator in prostate adenocarcinoma. Despite this significant clinical relevance, the determinants underlying disease aggressiveness in relation to GS remain largely unknown. To explore gene expression profiles among patients diagnosed with metastatic prostate adenocarcinoma, considering GS variation. Methods: This study is prospective in nature and was approved by CONEP-SCBH-CAAE 42638620.3.0000.5138. The study included 30 patients with histologically confirmed metastatic prostate adenocarcinoma who had not undergone any treatment. Patients were stratified into two distinct cohorts based on GS: low GS (GS <8) and high GS (GS ≥ 8). This design allowed for a more in-depth analysis of the associations between gene expression profiles and GS variations in the context of metastatic prostate adenocarcinoma. Results: The data show that 26.7% of patients (n=8) had a GS lower than 8, while 73.3% (n=22) had a GS equal to or greater than 8. In patients with a GS lower than 8, genetic profile analysis revealed that the ATM gene was expressed in three patients and the BRCA2 and TP53 genes were detected in one patient (n=1 for each gene). In relation to patients with GS equal to or greater than 8, the TP53 gene was expressed in 7 patients; the BRCA2, CHECK2, FANCL, RAD51C and RAD54L genes were expressed in only one patient (n=1 for each gene). These results indicate a more prominent expression of TP53 in patients with high GS, suggesting a relationship between the expression of this gene and the aggressiveness of metastatic prostate cancer with GS ≥8. In the sample, no positivity was observed for the BRCA1, CDK12, CHECK1, PALB2, PPP2R2A, RAD51B and RAD51D genes. Conclusions: The results show that metastatic prostate cancer patients with GS ≥8 exhibit elevated TP53 gene expression. The current sample of 30 patients provides preliminary insight, but the statistical robustness of these associations could be improved with a larger cohort. Carrying out subsequent studies with a broader sample will allow for a more reliable validation of the observed trends, contributing to a more comprehensive understanding of the associations between the analyzed variables and gene expression in patients with metastatic prostate carcinoma. Therefore, the interpretation of the results presented must be carried out with caution, considering the need for a more substantial sample size to verify and consolidate possible associations identified. Clinical trial information: CAAE42638620.3.0000.5138.
Comparison of prostate-specific antigen (PSA) response in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) vs abiraterone acetate (ABI): A real-world (RW) causal analysis.
Authors: Brown Gordon Andrew , Du Shawn , Khilfeh Ibrahim , Rossi Carmine , Diaz Lilian , Kinkead Frédéric , Lefebvre Patrick , Pilon Dominic , Ellis Lorie , Lowentritt Benjamin H 
Published: June 2024

e17070 Background: Patients with de novo mCSPC experience poor clinical outcomes which can be improved by treatment with androgen receptor signaling inhibitors (ARSIs). A prior RW study of patients with mCSPC initiated on APA or ABI found that APA initiators had significantly higher rates of PSA decline ≥90% (PSA90). This study compared PSA90 response by 6-months for patients with de novo mCSPC initiated on APA or ABI. Methods: Claims from the Komodo Health Solutions Research Database were linked with electronic medical records in US community urology practices from PPS Analytics. Exclusive APA and ABI cohorts were defined based on an initial pharmacy claim or dispensation for APA or ABI on or after 9/17/2019 (index date). Castration-sensitive patients were defined as de novo mCSPC if metastasis was observed ≤180 days after the initial prostate cancer (PC) diagnosis. Patients were also included if they had ≥12 months of pre-index clinical activity and had ≥1 PSA test within 13 weeks pre-index. Patients were followed until the earliest of index ARSI discontinuation (i.e., gap ≥90 days supply) or switch, radiopharmaceutical use, or end of clinical activity or data availability (9/30/2022). Inverse probability treatment weighting (IPTW) was used to balance pre-index covariates between cohorts (i.e., age, race, region, payer type, index year, time from metastasis to index date, time from first PC diagnosis to index date, metastasis location, use of androgen deprivation therapy, first-generation antiandrogens or chemotherapy, most recent PSA and testosterone levels, and earliest Gleason score). PSA90 was defined as the earliest ≥90% decline in PSA relative to the most recent value within 13 weeks pre-index. The proportion of patients achieving PSA90 by 6-months was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: A total of 356 APA and 324 ABI patients with de novo mCSPC were identified. Patient characteristics were balanced with IPTW (Table). By 6 months post-index, 82.0% of APA patients and 73.5% of ABI patients had a PSA measurement. By 6 months, significantly more APA patients attained PSA90 response relative to ABI patients (62.2% vs 41.6%; p<0.001; Table). Median time-to-PSA90 was 3.6 months for APA, and 10.3 months for ABI. Conclusions: This US-based RW study showed that a higher proportion of patients with de novo mCSPC initiated on APA achieved a deep, early PSA response relative to those on ABI. [Table: see text]
Can PSMA-PET be a better way to select patients for an intermittent treatment? Results from a prospective cohort.
Authors: Lages Dr. Paulo Sergio , Zulli Guilherme Augusto , Carcano Flavio Mavignier , Barbosa Michelle , Lages Luciana , Bergerot Paulo Gustavo , Rosa Diogo Augusto Rodrigues , Jardim Denis L. , Dias Mariane Fontes , Penna Coutinho Luiz Flavio , Vargas Pivato de Almeida Daniel 
Published: June 2024

e17073 Background: The current strategy for advanced disease is continuous androgen suppression, but new technologies such as PSMA-PET may set a rule for identifying some patients for new strategies. The addition of novel hormone agent (NHA) to systemic treatment of metastatic hormone sensitive prostate cancer (HSPC) has been associated with overall survival benefit and metastasis directed therapy (MDT) has been demonstrated benefit postponing ADT. There is an increasing volume of data on the use of fixed-duration NHA for patients with recurrent HSPC, most of whom are expected to present oligometastatic disease if PSMA PET/CT scans are used. We evaluate clinical outcomes of intermittent androgen deprivation therapy in patients with oligorecurrent or oligometastatic HSPC (or/omHSPC)treated with ADT + NHA + MDT, based on PSMA-PET imaging. Methods: This is a prospective cohort of patients with or/omHSPC treated with fixed-duration ADT + NHA in association with PSMA PET/CT-guided MDT (+ primary tumor irradiation if de novo metastatic) from a single institution in Brazil. Descriptive statistics was used in order to characterize the study population and relapse-free survival (RFS) after systemic therapy discontinuation (defined as PSA > 0.2 ng/mL for previous prostatectomy or > 2+nadir if presence of primary tumor in place) was assessed. Analysis of testosterone recovery and other clinic laboratorial factors were also performed. All patients had an undetectable level of PSA and a PSMA-PET with a complete response to be elegible to the intermittent treatment. Results: Between 2019 and 2023, 20 patients with or/omHSPC were treated with fixed-duration ADT + NHA and PSMA PET/CT-guided MDT. The median age was 64 years-old (range: 47-85), 11 patients presented with de novo omHSPC, and distribution across Gleason grades was: grade 1: 2, grade 2: 3, grade 3: 9, grade 4: 3, and grade 5: 2 patients. Metastasis were diagnosed on bone (7) and/or lymph nodes (19). Median PSA at treatment start for orHSPC population was 3.01 ng/mL (range: 0.15-14.74). The median total testosterone level prior to ADT start was 327 ng/dL (range: 22-494). Distribution across NHA was: abiraterone/prednisone: 13, enzalutamide: 4, apalutamide: 2, abiraterone>enzalutamide: 1 patient. With a median follow-up of 13 months after ADT + NHA discontinuation, no patient has progressed, with 54.5% of patients already presenting testosterone recovery. Conclusions: The results of this single-center prospective cohort incorporating PET-PSMA for inclusion and monitoring patients with oligometastatic and oligorecurrent disease suggests that intermittent androgen blockage is promising in the era of NHA.