bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey.
Authors: Cheng Li-Jen , Kim Janet , Mukherjee Apurba , Milloy Neil , Unsworth Mia , Ng Daniel
Published: March 2023

462

Background: Little is known about treatment and QOL of la/mUC in Saudi Arabia, South Korea, Turkey, and Taiwan. Therefore, this study assessed patient (pt), tumor, and disease characteristics; treatment sequencing; and QOL in pts with la/mUC treated in these countries. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world, multinational, point-in-time study using validated methodology (Anderson et al. Curr Med Res Opin. 2008;24:3063-72) and included physician surveys, chart reviews, and pt questionnaires (Saudi Arabia, Turkey, and Taiwan only). Data were collected (12/2021–3/2022) from oncologists and urologists and adult pts with confirmed la/mUC. EQ-5D visual analogue scale (VAS; scores: 0 [worst health] to 100 [best health]) and the global health status (QL2) from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (scores: 0 [low functioning] to 100 [high functioning]) questionnaires were used to assess QOL. Results: Data were provided by 175 physicians for 988 pts (Turkey, n=300; Saudi Arabia, n=240; South Korea, n=298; Taiwan, n=150) with la/mUC. Mean pt age was 66.3 y; 77% were men. Most (77%) pts had no family history of urothelial carcinoma (UC); 30% recorded no risk factors (eg, genetic risk, smoking, occupational exposure). At initial UC diagnosis, the bladder was the initial tumor location in 82% of pts, of whom 67% had la/mUC, and 83% of pts had an Eastern Cooperative Oncology Group performance status 0–2. At data collection, the most common metastatic sites were the lymph nodes (53%), lungs (29%), liver (27%), and bone (21%). Biomarker/tumor testing was not done in 45% of pts. In pts initially diagnosed with nonmetastatic UC (n=346), 28% received neoadjuvant and 31% received adjuvant therapy. Of pts receiving ≥1 line of therapy (LOT) for la/mUC (n=988), 74% received gemcitabine, 60% received cisplatin, 18% received carboplatin, 17% received a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor, and 4% received best supportive care (BSC) in the first-line (1L) setting; mean duration of therapy (DOT) in 1L was 5.7 mo. Of pts receiving ≥2 LOTs for la/mUC (n=290), 63% received a PD-1/L1 inhibitor and 35% received chemotherapy in the second-line (2L) setting; mean DOT in 2L was 4.9 mo. Of pts receiving ≥3 LOTs for la/mUC (n=87), 59% received chemotherapy (most often cisplatin [46%] or gemcitabine [38%]), 34% received a PD-1/L1 inhibitor, and 10% received BSC only in the third-line (3L) setting; mean DOT in 3L was 4.3 mo. Questionnaires were available for 319 pts. Mean (SD) EQ-5D VAS score was 51.8 (15.6); EORTC QL2 score was 44.6 (19.9). Conclusions: Pts with la/mUC in this multinational study generally received 1L platinum-based and 2L PD-1/L1 inhibitor therapies. These results highlight the need for therapies that improve clinical and QOL outcomes.
COVID-19 vaccines in patients with urothelial cancers receiving immune checkpoint inhibitors.
Authors: Gilbert Danielle , Hu Junxiao , Lam Elaine T.
Published: March 2023

491

Background: COVID-19 vaccination recommendations for cancer patients (pts) are similar to the general population. The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is the occurrence of immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. This retrospective study examined the incidence of severe irAEs in pts with bladder urothelial cancer (UC) treated with CPI therapy who received concurrent vaccinations against Sars-CoV-2. Methods: Following IRB approval, UC pts who received any approved CPI treatment since FDA authorization of the first COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received 1 or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (defined as one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation. Data was analyzed using descriptive statistics. Results: Forty pts were included in our analysis with a median age of 72.5 years (IQR: 66.0-79.2); 82% pts were male. At the time of vaccination, 37 pts (92.5%) received CPI monotherapy, 2 pts (5.0%) received combination (combo) CPI therapy, and 1 pt (2.5%) received combo platinum-based chemotherapy and CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 22 pts (55.0%), Moderna in 17 pts (42.5%), and Johnson and Johnson in 1 pt (2.5%). Number of vaccinations received was >/= 3 in 27 pts, 2 in 11 pts, and 1 in 2 pts. Six pts (15.0%) experienced severe irAEs following vaccination, including nephritis, colitis, pneumonitis, DKA, and infusion-related reaction. Rates of severe irAEs were 16.2% (6/37) with CPI monotherapy, no severe irAEs occurred in the combo CPI and combo CPI-chemo groups. Severe irAEs occurred after the first vaccine dose in 1 pt (16.7%), second dose in 3 pts (50.0%), and third dose in 2 pts (33.3%) pts. The median time between CPI treatment and vaccination in this group was 22.0 days (IQR: 15.8-36.5. Hospitalization was required for all 6 patients (100%). Three pts (50.0%) required immunosuppressive therapy with a median therapy duration of 64.0 days (IQR 47.0-83.5). Five pts (83.3%) discontinued CPI therapy following severe irAEs. Conclusions: In this retrospective study, we observed a 15% rate severe irAE in UC pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI. NCI University of Colorado Cancer Center Support Grant 5P30CA046934-30, Health Data Compass Data Warehouse project (healthdatacompass.org).
Quality of life in QUILT 3.032 study: Patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) receiving IL-15RαFc superagonist N-803 plus BCG.
Authors: Chamie Karim , Chang Sam S. , Kramolowsky Eugene V. , Gonzalgo Mark L. , Lechpammer Stanislav , Reddy Sandeep K. , Soon-Shiong Patrick
Published: March 2023

495

Background: Patients (pts) with BCG-unresponsive NMIBC have limited treatment options and are at an increased risk for cystectomy. Nogapendekin alfa inbakicept (NAI, also known as N-803), is an interleukin-15 superagonist (IL-15RαFc), which synergizes with BCG to elicit innate immune memory resulting in durable complete responses (CRs) in this patient population. In an open-label, 3-cohort, multicenter Phase 2/3 study of intravesical BCG plus NAI in BCG-unresponsive high-grade NMIBC (QUILT 3.032; NCT03022825), pts with carcinoma in situ (CIS; Cohort A) have a CR rate of 71% (median duration 26.6 months), 89.2% cystectomy avoidance and 100% bladder cancer specific survival at 24 months. We submit here the first quality of life (QOL) data report in the same pts cohort. Methods: Cohort A: 86 pts (median age 73 years; 87% male) with histologically confirmed BCG-unresponsive CIS with or without Ta/T1 disease, treated with intravesical BCG 50 mg plus NAI 400 μg. Mean baseline ECOG score was 0.183, with 82% of pts having score = 0. QOL was measured by the EORTC QOL Questionnaire Core 30 (QLQ-C30) and QOL NIMBC-Specific 24 Questionnaire (QLQ-NMIBC24). Results: Multivariate analyses have shown no significant changes over time for any of the measured QOL domains. Mild worsening vs. baseline in feeling ill was reported by 6% and 3% of pts by week 27 and 52, while 4% and 6% reported improvement. By week 78 and 104, 7% and 9% of pts reported improvement vs. baseline in their wellbeing with the majority being stable (non-significant). No statistically significant variations were detected in the physical function (PF) score (baseline vs. week 27, 52, 78 and 104). Higher PF scores were observed in pts responding to the therapy vs. non-responders; however, baseline value of PF was also higher in responders vs. non-responders. In contrast to historical results of BCG alone, week 27 physical function scores were numerically higher than baseline, with a subsequent nadir at week 78 and recovery to baseline by week 104 (non-significant). Hospitalizations for any reason remained low (0% - 6% per assessments) during the study. Conclusions: QOL measurement supports good tolerability of the intravesical NAI plus BCG in BCG-unresponsive, high-grade NMIBC pts with CIS. These results further strengthen the evidence of a favorable benefit: risk ratio of this novel combination immunotherapy, in a challenging disease. Clinical trial information: NCT03022825 .
Enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K.
Authors: O'Donnell Peter H. , Rosenberg Jonathan E. , Hoimes Christopher J. , Petrylak Daniel P. , Milowsky Matthew I. , McKay Rana R. , Srinivas Sandy , Friedlander Terence W. , Ramamurthy Chethan , Bilen Mehmet Asim , Burgess Earle F , Mar Nataliya , Moon Helen , Geynisman Daniel M. , George Saby , Carret Anne-Sophie , Yu Yao , Guseva Maria , Homet Moreno Blanca , Flaig Thomas W.
Published: March 2023

499

Background: In EV-103 Cohort K (NCT03288545), EV and P in combination (EV+P) showed encouraging antitumor activity and a manageable safety profile when used as 1L therapy in patients (pts) w/ la/mUC who are ineligible for cisplatin, a population w/ high unmet need. Here we report results of an analysis of prespecified Cohort K subgroups known to be associated w/ poor outcomes. Methods: Pts who are cisplatin-ineligible w/ previously untreated la/mUC were randomized 1:1 to EV (1.25 mg/kg) as monotherapy on Days 1 and 8 or in combination w/ P (200 mg) on Day 1 of 3-week cycles. Primary endpoint is cORR per RECIST v1.1 by blinded independent central review w/ no formal statistical comparison between arms. Secondary endpoints included duration of response and safety (e.g. treatment-related adverse events, TRAEs). The cORR analysis was performed in prespecified subgroups including age, ECOG PS, liver metastasis, PD-L1 expression status, metastatic disease site at baseline, and primary disease site of origin. Results: 149 pts were treated: EV+P n=76; EV n=73; cORRs across key subgroups for both EV+P and EV monotherapy are shown in the table. For EV+P overall cohort, cORR (95%CI): 64.5% (52.7, 75.1); median DOR was not reached. cORRs were consistent across subgroups for EV+P including those w/ ECOG PS score of 1-2: 62.8% (46.7, 77.0) and presence of liver metastasis: 53.8% (25.1, 80.8). Among TRAEs of special interest in the EV+P arm, skin reactions occurred in n=51 (67.1%); peripheral neuropathy occurred in n=46 (60.5%). For EV+P, 68.4% of pts had TRAEs leading to interruption of either EV or P; 48.7% of pts had TRAEs leading to EV dose reduction. Median duration of EV+P treatment was 11 cycles. Conclusions: EV+P showed promising cORR in 1L cisplatin-ineligible pts w/ la/mUC; activity was consistently observed across a range of pre-specified subgroups including those with poor prognosis. EV+P TRAEs were manageable w/ close monitoring and appropriate dose modifications w/ a meaningful duration of treatment. EV+P has the potential to address high unmet needs in 1L la/mUC and MIBC and is being further evaluated in 3 Phase 3 trials (NCT04223856, NCT04700124, NCT03924895). Clinical trial information: NCT03288545 . [Table: see text]
Updated experience on PSMA PET/CT for recurrent prostate cancer in a high-volume Brazilian center.
Authors: Lages Dr. Paulo Sergio , Monteiro do Prado Junior Luciano , Fonseca Monteiro do Prado Leonardo , Carvalho Oliveira Bruno , Ramos Barra Renato , Silva Barbosa Michelle , Vargas Pivato de Almeida Daniel ,   Latin American Cooperative Oncology Group Genitourinary Tumors Division, LACOG-GU
Published: March 2023

50

Background: PSMA PET/CT scan (68Ga-PSMA PET/CT) has emerged as a highly accurate tool when assessing disease staging both for newly diagnosed localized high-risk prostate cancer and for recurrent disease, with treatment plan modification in up to two-thirds of patients. Methods: We retrospectively reviewed the PSMA PET/CT scans results of patients undergoing the exam in all disease stages in a single institution in Brasilia, Brazil, between October 2015 and July 2022 and correlated clinicopathological information with test results for those in the recurrent disease setting. Results: Overall, more than 2,500 PSMA PET-CT scans were performed during the selected time interval. Any clinicopathological information was available for 648 patients, of whom 586 underwent the test in the setting of recurrent disease following treatment of primary disease. Positive results were found in 400 studies, with a median PSA level of 1.035 ng/mL (IQR 0.3–3.5) and most prevalent Gleason score of 7 (3+4). Metastatic disease was found in 26.2% of patients with a median PSA level of 4.61 ng/mL. Conclusions: A positive correlation between both PSA level and Gleason grade and the positivity rate of PSMA PET/CT was found in this large dataset, confirming the findings previously demonstrated in a prior presentation of our database. This result reinforces the importance of including more sensitive image methods when staging recurrent prostate cancer for the early detection of metastatic disease and adequate treatment planning. [Table: see text]
Neoadjuvant pembrolizumab for cisplatin-ineligible muscle-invasive bladder cancer prior to radical cystectomy.
Authors: Rose Kyle M , Bandini Marco , Huelster Heather L , Basile Giuseppe , Naidu Shreyas U , Spiess Philippe E. , Necchi Andrea , Li Roger
Published: March 2023

513

Background: There is an unmet need for systemic treatment options in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy. The PURE-01 trial has also demonstrated preliminary efficacy when pembrolizumab is used in the neoadjuvant setting. We aimed to compare pathologic response and survival outcomes in cisplatin-ineligible patients receiving neoadjuvant pembrolizumab (NAP) vs. immediate radical cystectomy (IRC). Methods: Cisplatin-ineligible MIBC patients were identified from the PURE-01 trial and compared against cisplatin-ineligible MIBC patients treated with immediate radical cystectomy (IRC). Overall survival was analyzed using Kaplan-Meier and Cox Proportional Hazards Modelling. IRC patients were matched via nearest neighbor propensity technique to cisplatin-ineligible patients from PURE-01 by ECOG status, GFR, age, sex, and clinical T stage. Results: Thirty-nine cisplatin-ineligible patients treated with NAP were identified from PURE-01, and compared against 313 cisplatin-ineligible patients undergoing IRC (Figure 1A). OS was prolonged in the NAP patients, with median survival of 19 months in the IRC vs. not reached (NR) in the NAP group (p=<0.01). Following nearest neighbor matching, 39 patients were identified from the IRC cohort, with comparable baseline clinicopathologic variables as listed in the table. Patients receiving NAP experienced a higher complete response rate on final pathology (pT0: 33% vs. 13%, p=0.03). Median OS was prolonged in the propensity score matched analysis (NAP NR vs. IRC 21.0mo, p<0.01), specifically at 12mo (89% vs. 57%), 24mo (64% vs. 28%), and 36 months after surgery (33% vs. 13% ) (p<0.01). Compared to NAP, cisplatin-ineligible patients undergoing IRC experienced worse OS, with a Hazard Ratio of 2.0 (95% CI 1.1 - 3.89). Conclusions: Cisplatin-ineligible patients receiving NAP for muscle invasive bladder cancer had a higher rate of downstaging and a survival advantage over patients who underwent IRC. Although this study suggests promising systemic options for cisplatin-ineligible patients in the neoadjuvant setting, results of ongoing prospective randomized trials will help validate these findings and provide therapeutic options to cisplatin-ineligible patients. [Table: see text]
Sequential enfortumab vedotin (EV) after platinum-based chemotherapy in metastatic or locally advanced urothelial cancer: Complete response, bladder preservation and survival.
Authors: Cen Putao , Chan Kok Hoe , Canfield Steven , Shu Tung , Maithel Neha , Tammisetti Varaha
Published: March 2023

529

Background: For metastatic or unresectable invasive urothelial cancer (UC), standard first-line platinum-based chemotherapy achieved progression-free survival (PFS) of 4–7 months. Complete response (CR) rate is <10%. The minority of patients downstaged after chemotherapy followed by cystectomy still suffer from loss of bladder function and a high risk of recurrence. To improve PFS, CR, and bladder preservation, we explored the use of EV after platinum-based chemotherapy in patients with metastatic or locally advanced UC who desired bladder preservation. Methods: Patients with metastatic or locally advanced unresectable UC who desired bladder preservation and received EV after platinum-based chemotherapy were identified. CR was defined as no evidence of disease identified on both radiology (MRI+CT) and cystoscopy; PFS were calculated from the date of initial treatment (first-line chemotherapy) to the date of last follow-up/death or recurrence via Kaplan-Meier analysis. Results: A total of 12 patients were identified: median age was 69.5 years (range, 52–83); 10 (83%) were men; 9 (75%) partial response and 3 (25%) disease progression were observed from platinum-based chemotherapy. EV was given after platinum-based chemotherapy to all 12 patients who subsequently achieved 100% of response: CR was achieved in 7 (58%) patients, and 4 (33%) remained disease free without ongoing treatment, their disease-free survival (DFS) was 9 months (range, 4–18); 2 patients who achieved CR then recurred as carcinoma in situ (CIS), one of whom had a cystectomy with TisN0 confirmed on final pathology. 2 (17%) patients received radiation to bladder and nodal area. Eleven (92%) patients retained their bladders and no patients died. Median follow-up was 19 months (range, 3.4–53.6). The median duration of EV was 7.5 months (range, 2–20). One-year PFS with bladder intact was 83%. Detailed clinical characteristics and outcome listed on Table. Conclusions: For patients with locally advanced or metastatic UC who desired bladder preservation, platinum-based chemotherapy followed by EV with or without pembrolizumab showed encouraging CR and PFS and deserves to be explored further. [Table: see text]
Pathologic response with neoadjuvant chemotherapy, immunotherapy, and chemo-immunotherapy for muscle-invasive bladder cancer (MIBC): A systematic review and meta-analysis.
Authors: Ayaz Ahsan , Naqvi Syed Arsalan Ahmed , Tripathi Nikita , Ijaz Hafsah , Mir Sajid Ahmad , Singh Parminder , Hussain Syed A. , Sonpavde Guru P. , McGregor Bradley Alexander , Bryce Alan Haruo , Riaz Irbaz Bin , Ravi Praful
Published: March 2023

531

Background: Neoadjuvant cisplatin-based chemotherapy (NAC) is established in the management of MIBC. Pathologic complete response (pCR, ypT0N0) and downstaging (<ypT2N0) are associated with long term survival in patients with MIBC. Several trials have evaluated neoadjuvant immunotherapy (NAI) and chemoimmunotherapy (NACI) for MIBC. We aimed to conduct a meta-analysis of available trials to compare the incidence of pathological response with NAC, NAI and NACI in MIBC patients undergoing radical cystectomy. Methods: Phase II/III clinical trials assessing neoadjuvant systemic therapies (NAC, NAI, or NACI) in patients with MIBC undergoing radical cystectomy were identified through a systematic search of MEDLINE and EMBASE. Outcomes of interest included pCR and pathological downstaging. A DerSimonian and Laird random-effect meta-analysis was conducted to estimate pooled incidence of events using the Freeman-Tukey transformation. Clopper-Pearson method was used to estimate the associated 95% confidence intervals (CI). Results: Of the 5357 records initially identified, 28 trials with a total of 2138 patients were considered eligible for inclusion. Neoadjuvant chemotherapy was assessed in 15 trials (1535 patients), NAI in 5 (288 patients), and NACI in 8 (315 patients). The pooled incidence of patients experiencing a pCR was 30.91% (95% CI: 26.54%-35.45%) with NAC, 30.92% (23.22%-39.14%) with NAI, and 42.25% (36.6%-48.0%) with NACI. The difference in pCR among these therapies was statistically significant (p <0.05). Similarly, the pooled incidence of achieving pathological downstaging was 40.91% (34.26%-47.72%) with NAC, 38.84% (26.73%-51.64%) with NAI, and 62.88% (57.22%-68.39%) with NACI. Consistently, there was statistically significant effect modification by the choice of neoadjuvant systemic therapy (p <0.01). The results were consistent across different clinically important subgroups (Table). Conclusions: NACI may achieve better pCR and pathological downstaging than NAC and NAI alone in MIBC patients which may potentially be associated with long-term survival. Definitive data from phase III trials are pending. [Table: see text]
Association of liver metastases, tumor microenvironment, and treatment outcomes in patients with urothelial bladder cancer treated with tislelizumab.
Authors: Xu Linlin , Liu Mo , Huang Ruiqi , Ma Xiaopeng , Wu Xikun , Ramakrishnan Vanitha , Zhang Lilin , Zhang Yun
Published: March 2023

537

Background: Tislelizumab, a humanized monoclonal antibody that targets programmed cell death protein 1 (PD-1), has shown promising activity in the treatment of advanced urothelial bladder cancer (UBC). Recent studies suggest that liver metastases (LM) are associated with reduced effectiveness of PD-1/PD-L1 therapies (Yu, et al. Nat Med. 2021;27[1]:152-164). We evaluated how LM correlate with survival outcomes and the tumor immune microenvironment in UBC patients treated with tislelizumab in the BGB-A317-204 trial (NCT04004221). Methods: Cox regression was used to evaluate the effect of LM on overall survival (OS). Other key baseline characteristics were further included as covariates in the model to investigate the adjusted effect of LM and the interactions of LM with them. Gene expression profiling and multiplex immunohistochemistry (mIHC) analysis were performed on baseline tumor samples. Gene expression differences between LM positive (LM+) and LM negative (LM–) patients were compared by Wilcoxon rank-sum test for continuous biomarkers, and Fisher’s exact test for categorical biomarkers. All P-values reported in this post-hoc exploratory analysis were descriptive, without multiplicity adjustment. A result of P<0.05 was considered statistically significant. Results: A total of 113 patients were included in the analysis. LM were present in 27/113 (23.9%) of them. Cox regression analysis showed the presence of LM was a negative prognostic factor for overall survival (OS) in UBC patients treated with tislelizumab, OS (hazard ratio (HR), 3.7; 95% CI, 2.3-6.2; P<0.001). The LM negative prognostic value remained unaffected after adjustment for other baseline covariates. Next, we investigated immune cell infiltration and gene expression as potential indicators of impaired response in LM+ patients included in this analysis. Significantly fewer circulating lymphocytes at baseline were found in LM+ compared to LM– patients ( P<0.05), while no differences were observed in other immune cell types. Reduced expression of gene signatures of CD4 Th1 ( P<0.05), CD8+T cells ( P<0.05) and NK cells functions ( P<0.05) within tumor tissues was observed in samples from LM+ patients. Reduced CD8+ T-cell infiltration within the tumor and the intra-tumor stroma was also observed in LM+ patients based on mIHC analysis. No significant differences were observed in tumor mutational burden level between LM+ and LM– patients. Conclusions: LM were associated with worse outcomes of UBC patients treated with tislelizumab in the A317-204 study. Diminished number and impaired function of CD8+ T cells and NK cells in the tumor microenvironment of LM+ patients may have contributed to the worse survival observed in this subset of patients. Clinical trial information: NCT04004221 .
Spatial immunophenotypes of distant metastases and response to immune checkpoint inhibition.
Authors: Erlmeier Franziska , Klümper Niklas , Strissel Pamela , Strick Reiner , Sikic Danijel , Bahlinger Veronika , Breyer Johannes , Ritter Manuel , Bolenz Christian , Roghmann Florian , Erben Philipp , Schwamborn Kristina , Wirtz Ralph M. , Horn Thomas , Wullich Bernd , Hölzel Michael , Hartmann Arndt , Gschwend Jürgen E. , Weichert Wilko , Eckstein Markus ,   BRIDGE Consortium e.V., Mannheim, Germany
Published: March 2023

538

Background: The value of PD-L1 to predict durable responses to immune checkpoint inhibition (ICI) in metastatic urothelial carcinoma (mUC) is inconsistent. We hypothesize that the use of archived primary tumor material (PRIM) for PD-L1 testing in clinical trials not properly reflecting the metastatic disease status (MET) contributes to this clinical issue. Objective: To analyze the predictive and prognostic value of PD-L1, spatial immunephenotypes and MHC-I determined in patient-matched PRIM/MET. Methods: PD-L1 (Ventana IC-Score, combined positivity score), spatial immunephenotypes (midi-plex digital spatial immuneprofiling) and MHC-I were examined in 154 mUC patients with at least one available pretreatment MET (138 patient-matched PRIM/MET pairs). 119 patients received first-line platinum-based chemotherapy, and 50 patients received second-line immunecheckpoint inhibition. PD-L1 expression, spatial immunephenotypes and MHC-I status of (patient-matched PRIM and) pretreatment MET were correlated to chemotherapy and ICI response and outcomes. Results: Discordance rates in patient-matched PRIM/MET amounted 25/30%, 36% and 49% for PD-L1 (CPS10/IC5%), immunephenotypes and MHC-I (loss versus preserved), respectively. Correlations with chemotherapy and ICI responses were observed for immunephenotypes and MHC-I status determined in MET (not for PD-L1 alone), but not in PRIM. In case of ICI, patients with cytotoxic tumor immune microenvironments (TIME) showed durable responses with disease control rates of 90% and a hazard ratio for disease progression/death of 0.05 (95%-CI:0.01-0.65) versus patients with immunedepleted MET (DCR 29%). MET MHC-I status added incremental value to predict durable ICI responses: Combination of MHC-I based (auto-)antigen expression of tumor cells with spatial immunepehnotypes in pre-treatment MET improved predictive and prognostic impact for response and outcome prediction of mUC patients undergoing first-line platinum-based chemotherapy and second-line immunecheckpoint inhibition. Limitations include the partly retrospective design and the lack of MET multisampling on individual patient level. Conclusions: The TIME is subject to substantial dynamics during metastatic evolution. MET immunephenotypes and MHC-I statuses show promising potential to predict chemotherapy and durable ICI responses, while the PRIM TIME does not. Thus, future clinical trials should rather rely on pre-treatment MET-biopsies reflecting the current immunological disease state than on PRIM.
Association of peripheral blood neutrophil-lymphocyte ratio (NLR) and red cell distribution width (RDW) with immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC).
Authors: El Zarif Talal , Thomas Jonathan , Riaz Irbaz Bin , Freeman Dory , Epstein Ilana , Nuzzo Pier Vitale , Davidsohn Matthew , McClure Heather , Matar Ayah , Kalluri Uttam , Yadav Ritu , Mantia Charlene , Ravi Praful , McGregor Bradley Alexander , Sonpavde Guru P.
Published: March 2023

540

Background: Determining a benefit from ICIs radiographically may take months and may be confounded by pseudoprogression. The NLR & RDW are readily accessible inflammatory markers from routine peripheral blood analysis and have been associated with outcomes in malignancies. We evaluated the association of early changes in NLR and RDW within 4 weeks after initiating ICI with any regression of tumor (ART) and overall survival (OS) in mUC. Methods: This study included de-identified data from Dana-Farber Cancer Institute in pts with mUC who were treated with ICIs from 2015 to 2020. Age, gender, setting (untreated vs. post-platinum), sites of metastasis (mets), performance status (PS), platelet count, RDW, and NLR at baseline and 3-4 weeks after initiating the ICI were collected. The primary objective was to assess the association of early increase in NLR by ≥1.0 from baseline or RDW at 3-4 weeks (as a continuous variable) post-ICI therapy with ART and OS. ART was assessed via subsequent imaging at any time point while on ICI. A multivariable logistic regression model and Cox proportional-hazards model were employed to identify the association of NLR changes with ART and OS, respectively, using backward selection. Results: A total of 330 pts were evaluable. The median age was 70 years, 72.1% (n = 298) were male and 69.4% (n= 227) received post-platinum ICI (remaining were platinum naïve). 46.5% (n = 146) experienced ART and the median OS was 13 months (11.14-16.14). An increase in NLR ≥ 1 in 3-4 weeks was associated with a lower rate of ART (OR: 0.41, 95% CI 0.24-0.70; p: 0.001) and worse OS (hazard ratio [HR]: 1.84, 95% CI 1.37-2.46; p < 0.0001) on multivariable analysis (Table). Higher RDW values at 3-4 weeks were associated with worse OS (HR: 1.08, 95% CI 1.03-1.14; p: 0.0004) but were not associated with ART. Conclusions: In pts with mUC initiating ICI, an early increase in NLR ≥ 1 and higher RDW in 3-4 weeks were associated with poor outcomes. Early changes in these readily available variables may enable early modification or intensification of therapy to improve outcomes. External validation of these findings is warranted. [Table: see text]
Immunohistochemical (IHC) subtypes of metastatic bladder cancer (mBC) using GATA3 and CK5/6.
Authors: Nelson Ariel Ann , Molina Nunez Mariel , Bylow Kathryn A. , Szabo Aniko , Iczkowski Kenneth , Kilari Deepak
Published: March 2023

557

Background: Genomic analyses have identified that bladder cancers can be divided into distinct molecular subtypes: luminal and basal. IHC markers GATA3 and CK5/6 have demonstrated >80% accuracy in assessing the luminal and basal subtypes of primary bladder tumors and may be easily utilized in clinical practice. Correlation of the primary bladder subtype with that of metastatic sites has not been demonstrated and associations with clinical outcomes are uncertain. Methods: We retrospectively identified patients with mBC who were treated with systemic therapy and had biopsies of either primary bladder or metastatic sites. Patient demographic, metastatic sites, treatment patterns, and clinical outcomes were recorded. Tissue microarrays (TMA) were constructed from primary and/or metastatic tumors. IHC was performed using mouse monoclonal antibodies: GATA-3 (L50-823, Pharmingen, 1:200) and cytokeratin 5/6 (XM26, Thermo Fisher, 1:100). Luminal (GATA3+, CK5/6-), basal (GATA3-, CK5/6+), double positive (GATA3+, CK5/6+) or double negative (GATA3-, CK5/6-) subtyping was applied. Concordance of matched bladder and metastatic pairs was quantified using Cohen’s kappa. Wilcoxon rank-sum tests were used for comparison of continuous and ordinal measures and chi-square tests were performed for comparison of categorical measures. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. Results: Of 62 specimens, 37 bladder and 16 metastatic sites were interpretable. Four IHC subtype patterns were identified, most were luminal (n=20) followed by double-positive (n=12), basal (n=5), and double-negative (n=5). Of 10 pairs of matched primary tumor and metastatic sites, there was near-perfect subtype concordance between primary and metastatic tumors (κ=0.84; 95% CI:0.58-1.00). No association between sites of metastatic progression and subtype were identified, nor was there any difference in overall survival between the subtypes (p = 0.70). The basal subtype had numerically worse survival compared to the luminal subtype, HR =0.164 (95% CI: 0.02-1.58, p=0.12). Conclusions: IHC subtyping by GATA3 and CK5/6 is feasible in the clinical setting and showed strong correlation between primary and metastatic sites. A larger analysis is planned to further investigate associations with clinical features and outcomes. [Table: see text]
Clinical outcomes after utilization of PSMA PET scans in patients with biochemical recurrent prostate cancer.
Authors: Tsung Irene , Hynes Stephen , Joshi Urvashi Mitbander , Morales Krystal A , Dess Robert Timothy , Jackson William C. , Taylor Jeremy MG , Reichert Zachery R
Published: March 2023

57

Background: The optimal management of biochemical recurrent prostate cancer (BCR) remains unknown. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans can visualize micrometastatic disease, thus expanding treatment options for BCR from observation or androgen deprivation therapy (ADT) to potentially include metastasis-directed radiation (XRT) or next-generation hormonal agents (NHA). We aimed to describe how BCR patients were managed after PSMA PET scans and their clinical outcomes. Methods: We performed a retrospective chart review of 262 patients from the University of Michigan’s PSMA PET scan database (825 patients with scans 2017–2021). Patients who received maximal local therapy (defined as XRT alone n=199 or surgery + XRT n=63) are presented. Only patients with BCR and a minimum of 1 year follow-up after scans were included. Baseline patient and tumor characteristics, PSMA PET scan results, first and subsequent therapy delivered after PSMA PET, and prostate-specific antigen (PSA) and standard imaging results post PSMA PET were annotated. Primary endpoint is time from first post-scan therapy (within 6 months of scan) to subsequent therapy. Secondary outcomes include probability of no subsequent therapy in 1 year based on first post-scan therapy and PSMA scan findings and PSMA PET findings and association with Gleason score, PSA at BCR, and time from diagnosis to PSMA scan. Results: Of 262 patients with maximal local therapy, 115 met inclusion criteria. Primary definitive treatment was XRT alone in 58% and surgery + XRT in 42%. Median PSA at time of scan was 4.4 ng/mL, and PSMA PET was positive in 87%. First therapy rendered after PSMA PET included 15% no therapy, 26% XRT only, 28% systemic therapy only (ADT +/- NHA), 27% combination therapy (XRT +/- systemic), and 4% other. Subsequent therapy was given in 26%. The median time from first to subsequent therapy was 41 months in patients who received XRT alone as first therapy and not reached for those with combination XRT + ADT. None of the 33 treated with combination therapy required subsequent therapy in 1 year. Remainder of analyses incomplete due to small sample sizes. Results to be updated by time of symposium. Conclusions: This observational study characterizes longer term clinical outcomes in patients with BCR who undergo various therapies after PSMA PET scans. Data may inform current decision making while prospective clinical trial data is awaited.
Comprehensive gene sequencing to identify progression predictors to muscle-invasive bladder cancer.
Authors: Cyrenne Jocelyne Brianna , Kanjeekal Sindu Mary , Porter Lisa , Cavallo-Medved Dora , Fifield Bre-Anne , Rueda Luis , Atikukke Govindaraja , Alkhateeb Abedalrhman , El-Gohary Yasser
Published: March 2023

570

Background: Over 8900 Canadians are diagnosed with bladder cancer every year, ranking it the fifth most frequent cancer. It can manifest as either non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC). The majority of patients initially receive a diagnosis of NMIBC, although high-grade NMIBC has a 50–70% recurrence rate and 10–30% chance at progressing to MIBC. The transition from high-grade NMIBC to MIBC is poorly understood, and there are currently no accurate biomarkers that predict disease progression. We propose a comprehensive molecular characterization to pinpoint specific copy number alterations (CNAs) related to either MIBC or NMIBC, and hence define the molecular development. Methods: This study analyzed a public dataset from MSKCC and 30 bladder cancer patient samples from Windsor Regional Hospital, both containing NMIBC and MIBC samples. Comprehensive gene sequencing was performed, and CNAs were obtained in over 500 common tumour gene panels. Results: Preliminary data from this study found MIBC may be predicted with 91% accuracy and 95% precision using CNA values of TP53, DDR2 and MLL2. In particular, MIBC correlates with gain of DDR2 or MLL2. Importantly, it has been demonstrated that high expression of DDR2 is associated with a worse prognosis. A panel of bladder carcinoma cell lines were used to validate the DDR2 findings. DDR2 values were quantified across the panels and corresponded with proliferation and invasiveness of cell lines. DDR2 was examined as a possible therapeutic target. Conclusions: Taken together, these findings provide insight to the pathogenesis of muscle invasion in bladder cancer. The potential to identify "genomic triggers" for the transition was facilitated by creating a genetic profile at these two stages.
Radical nephrectomy in medically underserved patients: Selection bias and disparity in surgical health care delivery.
Authors: Shah Aastha , Ghassemzadeh Saeed , Puri Dhruv , Meagher Margaret , Liu Franklin , Nguyen Mimi , Hakimi Kevin , Dhanji Sohail , Wang Luke , Javier-Desloges Juan , Derweesh Ithaar H
Published: March 2023

609

Background: Disparities in outcomes of renal cell carcinoma (RCC) exist with respect to survival outcomes between different ethnic, and socioeconomic groups. We sought to evaluate disparities in delivery of surgical care between medically underserved (MU) and non-medically underserved (NMU) patients. Methods: We conducted a single-center retrospective analysis of consecutive patients presenting with localized renal cortical neoplasms who underwent surgical excision [Radical (RN) or Partial Nephrectomy (PN)] at an academic tertiary-care referral center. The cohort was divided into MU and NMU groups and descriptive analyses were conducted for demographics and clinical disease characteristics, type of surgery, time to surgery, estimated blood loss, and 30-day total and major complications (Clavien-Dindo, ≥3). Cochran-Armitage trend analysis was conducted to evaluate for surgical trends, and logistic regression multivariable analyses (MVA) were conducted for type of surgery and major complications. Results: 1418 patients were analyzed (MU n=334/NMU n=1084). Comparing MU vs. NMU, no differences were noted for age (p=0.612), Charlson Comorbidity Index (p=0.803), tumor size (p=0.236), or time to surgery (p=0.482). Significantly greater proportions of white patients were noted in NMU (60.6% vs. MU=45.5%, p<0.001) and higher proportion of RN in MU (47% vs. NMU=40.4%, p=0.028). Subgroup analyses of PN groups revealed no differences with respect to demographics, tumor size (p=0.33), major complications (p=0.66), or blood loss (p=0.583). Subgroup analysis of RN revealed significantly higher proportion of non-white patients (p=0.019) and patients with diabetes (p=0.019). MVA for predictors for receipt of RN were non-white (OR1.4, p=0.002), MU (OR=1.32, p=0.043), age (OR=1.01, p=0.009) and treatment year (OR=0.913, p<0.001). MVA for predictors for 30 day major complications demonstrated RN (OR=0.913 p<0.001). Cochran-Armitage trend analysis indicated that both MU and NMU had significant increases in PN between 2003 and 2021 (p<0.0001). Conclusions: Despite overall similarities with respect to demographics and clinical disease characteristics and time to surgery, MU status was associated with a significantly higher odds of receiving a RN at a tertiary care referral center, which represents a disparity in care and possible selection bias. Nonetheless, RN was also associated with a decreased risk of complications. While trends have demonstrated an increase in proportion of PN for both NMU and MU groups, comparative underutilization of PN in MU patients may be associated with increased downstream risks to health. Further investigation is requisite.
Does body mass index matter in predicting renal mass sizes? Comparison of imaging modalities.
Authors: Son Young , Fink Benjamin , Thomas Brian , DeVincentz Dayna , Dalton Raeann , Mueller Thomas , Brown Gordon Andrew
Published: March 2023

619

Background: Renal cell carcinoma is most commonly diagnosed as an incidental mass detected on cross sectional imaging. When a renal mass is thought to be cancerous, size on imaging is important for clinical decision-making, as there is a known positive correlation with increasing size prognostic outcomes. Image quality may be adversely impacted by a variety of factors, and we sought to assess the impact of body mass index (BMI) on the ability to obtain accurate renal mass sizes across multiple imaging modalities. Methods: A retrospective multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between January 2018 and December 2021 from three different hospitals and six operating surgeons. BMI groups were assigned by BMI 1: <18.5, BMI 2: 18.5-24.9, BMI 3: 25-29.9, BMI 4: 30-34.9, and BMI 5: >35. Differences between greatest dimensions were compared between pathological measurement and each imaging modality: computerized tomography (CT) with and without contrast, ultrasound (US), and magnetic resonance imaging (MRI). Paired t test was used to analyze the total cohort mean difference testing for a difference between modalities and pathology report. T-tests and Wilcoxon signed-rank tests were used to compare the different BMI groups. Results: A total of 234 patients met inclusion criteria and were identified by age, gender, procedure, and renal mass location. There was a statistically significant difference between the greatest dimension as measured on CT with contrast and MRI compared to pathological measurement in the total cohort. Sub analysis of BMI groups showed the differences in size in BMI group 4 (mean (SD)) (0.46 cm (0.52)) and BMI group 5 (0.4 cm (0.51)) were found to have a significant difference in size estimates compared to BMI 3 for CT with contrast (Table). There was no difference for size estimates by BMI group for any other imaging modality. Conclusions: While CT with contrast and MRI are important modalities for their tissue enhancement abilities, they may not be the strongest choice for strict renal mass size estimation. Specifically, CT with contrast becomes less accurate at estimating mass size for patients with BMI >30. [Table: see text]
Novel retroperitoneal neovascularity scoring system in renal cell carcinoma tumor staging.
Authors: Fateri Cameron , Peta Akhil , Bui Thahn-Lan , Kar Nina , Roth Bradley , Park Sung-Mee , Glavis-Bloom Justin , Houshyar Roozbeh , Landman Jaime
Published: March 2023

620

Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer worldwide. While radiologists assess enhancement patterns of renal tumors to predict tumor pathology, to our knowledge, no formal scoring system has been created and validated to assess the level of neovascularity in RCC, despite its critical role in cancer metastases. In this study, we characterized and analyzed the level of angiogenesis in tumor-burdened kidneys and their benign counterparts. We then created and validated a scoring scale for neovascularity that can help predict tumor staging for RCC. Methods: After Institutional Review Board approval, the charts of patients who had undergone surgery for RCC between January 13, 2014 and February 4, 2020 were retrospectively reviewed for inclusion in this study. Inclusion criteria were a diagnosis of RCC, simple/radical nephrectomy, pre-operative contrast enhanced computed tomography (CT) scans, and complete pathology reports. Neovascularity was scored on a scale of 0 to 4 where 0= no neovascularity detected, 1= a single vessel <3mm wide, 2= a single vessel >3mm wide, 3=multiple vessels <3mm wide, and 4=multiple vessels >3mm wide Results: A total of 227 patients were included in the study. The majority of tumor pathology was clear cell carcinoma, regardless of tumor staging. The average neovascularity score was 1.07 for pT1x tumors, 2.83 for pT2x tumors, and 3.04 for pT3x tumors. There was a significant difference in neovascularity score between pT1x and pT2x tumors (p = 0.0046), pT1x and pT3x tumors (p < 0.0001), and benign kidneys and kidneys with RCC (p = <0.0001). Furthermore, we sought to address the ability of the Re-VASC score to predict up-staging or down-staging of clinically staged tumors. Only 5 total tumors were upstaged from cT1 to any pathological stage >1, with an average Re-VASC score of 2.33. There were 24 cases that were down-staged to pT1, with an average Re-VASC score of 1.73. Additionally, we specifically looked at cT3a tumors that were down-staged to p1x. The average Re-VASC scores were 0.82 and 2.11 for pT1a and pT1b tumors respectively. Conclusions: Our novel vascular scoring system for renal cell carcinoma demonstrates significant correlation with RCC pathological tumor staging. In future studies, we would like to further explore the ability of the scoring system to predict clinical up-staging and down-staging, as we had a limited sample size to analyze this function. This scoring system may be utilized as part of a comprehensive radiological assessment of renal tumors, potentially improving tumor characterization and clinical decision making.