tbuckley/cabot-search huggingface dataset:
Influential factors impacting treatment (tx) decision making (TDM) and decision regret (DR) in patients (pts) with localized or locally advanced prostate cancer (LPC/LAPC).
Authors: Benjamin Adam Gartrell, Angaja Phalguni, Suneel Mundle, Sharon McCarthy, Sabine D. Brookman-May, Francesco De Solda, Ruhee Jain, Guillaume Ploussard, Boris A. Hadaschik
Journal: Journal of Clinical Oncology (2024)

294 Background: Pts newly diagnosed with LPC/LAPC must contemplate many factors to make tx decisions that may later lead to regret. We conducted literature reviews exploring factors associated with pt TDM and DR. Methods: Databases (Ovid Medline, Ovid Embase, Cochrane Library), select congress proceedings and gray literature were searched (12 Sept 2022). Publications (pubs) on pt TDM and tx DR in LPC/LAPC were included following systematic literature review methods and selected based on the following criteria: 2012 onward, ≥100 pts, journal article, and quantitative data. Study quality was assessed by risk of bias tools (NICE STA guidance; Newcastle-Ottawa). Influential factors were those with p&lt;0.05; for TDM, factors described as “a decision driver,” “associated,” “influential,” or “significant” were also included. Key factors were determined under consideration of number of studies, consistency of evidence, and study quality. Results: 75 pubs (68 studies) reported TDM (12 countries; 68% North America [NA] 25% Europe [E]). Pt TDM participation was reported in 34 pubs; overall, pts preferred an active/shared role. Of 39 influential TDM factors, those related to baseline demographics, health and disease, external factors (doctor recommendation most common), and tx goals/attributes were key (Table). 49 pubs reported DR (12 countries; 59% NA, 29% E). DR was assessed at 2 weeks to 6 years post-tx. Not tx specific DR (23 studies), was felt by 8-48% of pts. Regret associated with specific tx (18 studies) was felt by 7-43% (active surveillance), 12-57% (radical prostatectomy), 1-49% (radiotherapy), 28-49% (androgen deprivation therapy), and 21-47% (combination therapy) of pts. Of 42 significant DR factors, tx toxicity (sexual/urinary/bowel dysfunction), pt role in TDM, and making an informed tx decision were key (Table). Conclusions: DR is common in pts with LPC/LAPC. To help pts navigate factors influencing TDM and limit risk of DR, a shared consensual TDM approach between pts, caregivers, and healthcare professionals is needed. [Table: see text]
The risk of prostate cancer diagnosis in men with an elevated PSA but low IsoPSA.
Authors: Nour Abdallah, Tarik Benidir, Andrew Wood, Zaeem M Lone, Rebecca Campbell, Ao Zhang, Onuralp Ergun, Caleb Curry, Ross Liao, Patrick Michael, Samuel Haywood, Zeyad Schwen, Ruben Olivares, Jihad Kaouk, Robert Abouassaly, Eric A. Klein, Christopher Weight
Journal: Journal of Clinical Oncology (2024)

292 Background: IsoPSA is a structure-based serum assay. Initial studies demonstrated that it outperformed total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (i.e., grade group (GG) ≥2) on biopsy. This led to an overall reduction in invasive testing and magnetic resonance imaging (MRI). We sought to compare the risk of csPCa in patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients (n=1578) who underwent IsoPSA testing from November 2016 to August 2022. Data was dichotomized into patients with normal (≤6) and high IsoPSA (&gt;6). We collected the outcomes of any follow-up IsoPSA, prostate biopsy, MRI, and diagnosis of prostate cancer. In the case of multiple follow-up tests, the most recent one was recorded. Results: The median follow-up time of 1578 patients who underwent IsoPSA testing was 24 months (IQR 16-29). Among 541 patients with an initial normal IsoPSA, 60 (11.1%) had a subsequent high IsoPSA, 23 (4.3%) had csPCa on a subsequent biopsy, and 48 (8.9%) had suspicious lesions on MRI (PI-RADS 4-5). Among 1037 patients with an initial high IsoPSA, 366 (35.3%) had csPCa on a subsequent biopsy and 342 (33%) had suspicious lesions on MRI. The sensitivity of IsoPSA to predict csPCa was 94.1%, and its negative predictive value was 89.3%. Conclusions: With 24-month follow-up, 4.3% of patients with normal IsoPSA developed csPCa, suggesting that a low baseline IsoPSA provides durable information about the 2-year risk of csPCa.[Table: see text]
Survival and comorbid diabetes mellitus in metastatic hormone-sensitive prostate cancer.
Authors: Priya Baxi, Daniel B. Eaton, Varun Puri, Martin W. Schoen
Journal: Journal of Clinical Oncology (2024)

74 Background: Diabetes is increasing in prevalence and management of comorbid disease in cancer is important for outcomes. Comorbid diabetes mellitus in patients with metastatic hormone sensitive prostate cancer (mHSPC) is important to consider as cancer treatments can adversely affect metabolic health and have added interactions with diabetes medicines. Little is known about the comparative effectiveness of diabetes management with insulin or oral medications. We aim to assess the survival of patients with comorbid diabetes based on insulin, oral, or no medication management. Methods: Patients diagnosed with mHSPC from 2000-2021 were identified within the Veterans Health Administration. Uncomplicated or complicated diabetes was determined using Charlson codes from the International Classification of Diseases. Treatment was determined by prescriptions of insulin, oral medication, or no use in VHA prescription records in the year prior, up to 14 days before diagnosis. Kaplan-Meier, ANOVA, and Cox proportional hazard models were used to analyze the data and covariates such as body-mass index, age, race, and baseline PSA. Results: Patients with mHSPC had significant differences in survival with diagnosis of diabetes, see table. Patients with complicated diabetes had a higher mean BMI than patients with uncomplicated diabetes (28.3 vs. 29.1, p &lt;.001). In patients with diabetes (n = 4740), insulin was used in 1091, oral medication in 1833, or no medicines in 1816. Oral diabetes medication was associated with improved survival compared to insulin and no medication use had the lowest survival (26.6 months vs. 24.3 vs. 21.9, p &lt;0.001). In an adjusted multivariable model, both insulin and oral medicine use were associated with increased risk of death with adjusted Hazard Ratio (aHR) for insulin 1.25 (95% CI 1.17-1.35), for oral medicine aHR 1.11 (95% CI 1.05-1.18). Conclusions: Among veterans with mHSPC, diabetes was associated with decreased survival. Within patients with a diagnosis of complicated or uncomplicated diabetes, the use of oral medication was associated with longer survival compared to insulin. Further assessment of the management of comorbid diabetes may help guide treatment and prevent adverse events. [Table: see text]
Phase 3 KEYNOTE-676 cohort A: Bacillus Calmette-Guérin (BCG) with or without pembrolizumab for high-risk (HR) non–muscle-invasive bladder cancer (NMIBC) that persists/recurs after BCG induction.
Authors: Neal D. Shore, Hiroyuki Nishiyama, Shahrokh F. Shariat, Gary Steinberg, Ashish M. Kamat, Shaheen Riadh Alanee, Kijoeng Nam, Kentaro Imai, Ekta Kapadia, Noah M. Hahn
Journal: Journal of Clinical Oncology (2024)

TPS722 Background: Intravesical instillation of BCG is a standard-of-care treatment for patients with HR NMIBC, but up to 50% of patients later experience disease recurrence or progression to muscle-invasive bladder cancer (MIBC) despite BCG treatment. In the phase 2 KEYNOTE-057 study (NCT02625961), pembrolizumab monotherapy was shown to have antitumor activity in patients with HR BCG–unresponsive NMIBC who had carcinoma in situ (CIS) with or without papillary tumors and in patients with only papillary tumors. In cohort A of the randomized, phase 3 KEYNOTE-676 trial (NCT03711032), pembrolizumab plus BCG versus BCG alone is being evaluated in patients with persistent/recurrent HR NMIBC after first BCG induction. Methods: Key eligibility criteria include adults with histologically confirmed HR NMIBC (T1, high-grade Ta, and/or CIS) that is persistent/recurrent following 1 adequate course of BCG induction therapy, have no concurrent extravesical disease or history of extravesical disease that recurred within 2 years, have an ECOG PS score of 0 to 2, and have undergone cystoscopy/TURBT ≤12 weeks before randomization. Approximately 430 patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg intravenously every 3 weeks plus BCG or BCG alone. BCG (50 mg) will be administered by intravesical instillation as induction therapy once weekly for 6 weeks and then as maintenance therapy once weekly for 3 weeks at weeks 13 and 25, then every 24 weeks (Q24W) thereafter. Treatment will continue for approximately 2 years (pembrolizumab) or 3 years (BCG), or until confirmed persistent/recurrent HR NMIBC or disease progression to MIBC or metastatic bladder cancer, unacceptable toxicity, or withdrawal. Randomization to treatment will be stratified by PD-L1 combined positive score (≥10 or ˂10), histology (CIS or non-CIS), and NMIBC disease history (persistence/recurrence 0 to ≤6 months or recurrence ˃6 to ≤12 months or recurrence ˃12 to ≤24 months). Response will be assessed by local cystoscopy and blinded independent central review of urine cytology and biopsy (as applicable) every 12 weeks for years 1 to 2 and Q24W for years 3 to 5. Computed tomography urography will occur every 72 weeks through year 5, then every 104 weeks thereafter. The primary end point is complete response rate in patients with CIS. Secondary end points are duration of response in patients with CIS, event-free survival, recurrence-free survival, time to cystectomy, overall survival, disease-specific survival, safety and tolerability, and patient-reported outcomes. Enrollment incohort A of KEYNOTE-676 is ongoing in Asia, Australia, Europe, and North America. Clinical trial information: NCT03711032 .
Kidney cancer metastases to breast and other genitourinary (GU) organs: A pooled analysis.
Authors: Phillip Taboada, Matthew Lee, Parker Smith, Jue Wang
Journal: Journal of Clinical Oncology (2024)

401 Background: As the number of kidney cancer survivors increases, the appearance of second malignancies and unusual metastatic patterns is increasing. We performed a pooled analysis to assess the clinicopathologic findings, treatment, and outcomes of cases involving breast and GU organs. Methods: Pooled analysis of published case reports and case series of renal cell carcinoma (RCC) metastasis to breast and genitourinary (GU) organs, including four cases from our institution. Parameters were compared between GU organ cohorts using a one-way ANOVA test and subgroup analysis. Results: 127 patients with GU metastasis of RCC were analyzed. The overall mean age was 61.2 years (Range: 14-92). GU organs with reported metastasis included 24 to testis (18.9%), 18 to penis (14.2%), 18 to breast (14.2%), 17 to vagina (13.4%), 17 to bladder (13.4%), 14 to ovary (11%), 7 to prostate (5.5%), and 6 to urethra (4.7%). Median Fuhrman grade was 2.5 overall, with penis metastases (n=4) having a median grade of 4. 95 of 111 (86%) cases reported patients with GU metastasis that had a prior nephrectomy for RCC. Patients with breast metastasis (n=16) had a significantly longer time between nephrectomy and metastatic diagnosis (90.1±63.1 months) than penile (12.7±16.1 months, n=6, p&lt;0.01), bladder (28.7±26.6 months, n=15, p&lt;0.01), or vaginal cohorts (6.7±5.2 months, n=3, p&lt;0.05). Co-metastasis to extra-GU sites were most prevalent in penile metastasis (47.4%, n=9). The primary treatments for metastases were excisional surgery (79%), immunotherapy (18%), radiotherapy (14%), and tyrosine kinase inhibitors (13%). The breast cohort (n=10) reported a 90% survival rate at final follow-up, while the vaginal (n=8) and penile (n=12) cohorts reported survival rates of 50%. The urethra cohort (n=2) had a median survival time of 53 months, while the breast cohort (n=10) had a median survival time of 6 months. Conclusions: While kidney cancer's metastasis to other GU organs is relatively uncommon, it presents unique diagnostic and therapeutic challenges. Recognizing these patterns and understanding the biology behind such spread can offer insights into RCC's behavior and drive more effective treatments. [Table: see text]
HRR testing and PARPi utilization among patients with metastatic castration resistant prostate cancer treated in the real-world setting.
Authors: Anupama Vasudevan, Harvey I. Katzen, Mike Gart, Simon Blanc
Journal: Journal of Clinical Oncology (2024)

91 Background: HRR mutations (HRRm) have prognostic value in metastatic castration-resistant prostate cancer (mCRPC). Treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) has shown better outcomes among patients with HRR mutations. This study aimed to understand the HRR testing rates among mCRPC patients and utilization of PARPi(s) among HRRm mCRPC patients treated in the real world. Methods: A random sample of 480 mCRPC patients from the Integra Connect PrecisionQ de-identified database were included in this retrospective observational analysis with additional information supplemented by curation. The database contains ~80% community oncology and ~20% academic practices with over 2 million cancer patients across 500 sites of care. Eligible male patients were those aged ≥18 years, diagnosed with mCRPC, and who received treatment between 2020 and 2023. HRR testing rates and utilization of PARPi use were assessed and presented for this study. Results: The mean (SD) age of 480 mCRPC patients was 76.9 (8.3) years; 78.3 % reported being White, 7.9% as African American, 1% as Asian, and 12.7% as Other. Most of the patients reported a payer type of Medicare/Medicaid (69.2%) followed by 15.6% Commercial and 15.2% as Self-Pay/Other. Testing for HRR was reported in 235 (48.9%) of the mCRPC patients and 59 (25.1%) of those patients were HRRm. The mean (SD) age of 59 HRRm mCRPC patients was 77.1 (7.2) years; 88.1% were white, 6.8% African/American, and 5.1% Other. Payer type was reported as being Medicare/Medicaid in 72.9% followed by 18.6% Commercial and 8.5% as Self-Pay/Other. BRCA and ATM mutations were reported among 22/59 (37.2%) and 15/59 (25.4%) patients, respectively. Among the 59 HRRm mCRPC patients, 53 (90%) were noted to have received prior NHA (novel hormone agents) while only 36/53 (67.9%) were noted to have received PARPi. Conclusions: Fewer than half of those patients with mCRPC were tested for HRR. This highlights the lack of testing among those receiving care in a real-world setting. The underutilization of PARPi in these patients is a missed potential opportunity for improving their outcomes.
Real-world genomic testing patterns in patients with prostate cancer.
Authors: Dalia Kaakour, Nataliya Mar
Journal: Journal of Clinical Oncology (2024)

97 Background: The armamentarium of therapies for metastatic prostate cancer (PCa) has now expanded to include genomically targeted agents and CPIs. Men with both somatic and germline alterations in the DNA damage repair (DDR) pathway, most commonly BRCA2, are candidates for PARP inhibitors. Recent data from the PROPEL and MAGNITUDE trials led to approval of PARP inhibitors in combination with novel hormonal therapies earlier in the PCa continuum, in the first-line metastatic castrate-resistant space. Some PCas harbor genomic alterations, such as TMB&gt;10 m/Mb and MSI high, which predispose to increased responses to CPIs, leading to tumor agnostic approval of pembrolizumab in these patient populations. However, it is imperative to perform timely genomic testing to assess for presence of these alterations. Methods: We conducted a 15-question survey using the Qualtrics XM software to assess genomic testing patterns of various providers in academic and community settings managing PCa patients. The survey link was distributed electronically to providers predominantly in the Western United States. Results: A total of 47 survey responses were received, with 59.6% (28/47) self-identifying as medical oncologists (Onc), 21.3% (10/47) as urologists (Uro), 4.3% (2/47) as radiation oncologists, 8.5% (4/47) as advanced practitioners, and 6.4% (3/47) as other. Academic Onc comprised 23.4 % (11/47), community Onc comprised 36.2% (17/47), academic Uro comprised 17.0% (8/47), and community Uro comprised 4.6 % (2/47) of providers. Timing of ordering of germline and somatic genomic testing by selected provider type is outlined in the Table. Conclusions: Given availability of targeted therapies in PCa management, ordering germline and somatic germline genomic testing is imperative. Despite the small sample size, several trends emerge from this dataset. Oncs at academic centers tend to order genomic testing earlier than Oncs at community practices, while Uros were less likely to order genomic testing when compared to Oncs in general. [Table: see text]
Factors predictive of primary resistance (PrimRes) to immune checkpoint inhibitors (ICIs) in patients (pts) with metastatic urothelial cancer (mUC).
Authors: Nikhil Pramod, Scott Dawsey, Ubenthira Patgunarajah, David Lynn, Wei Wei, Charbel Hobeika, Monica Nair, Allison Martin, Kimberly Maroli, Moshe Chaim Ornstein, Christopher Eing Wee, Timothy D. Gilligan, Amanda Nizam, Amanda Bonham, Omar Y. Mian, Paul G. Pavicic, C. Marcela Diaz-Montero, Shilpa Gupta
Journal: Journal of Clinical Oncology (2024)

703 Background: Response rates to ICIs in pts with mUC remain modest at around 20% and there are no reliable biomarkers to select pts most likely to respond to ICI. It is an unmet need to define factors associated with PrimRes (progressive disease (PD) clinically and/or radiologically after at least 2 cycles of ICI) to spare pts from unnecessary treatment and the associated physical and financial toxicity. PrimRes to ICI has not been well defined in mUC pts and we sought to study predictive factors in our real-world cohort. Methods: We retrospectively reviewed 335 pts at the Cleveland Clinic who received ≥ 2 cycles or at least 6 weeks of ICI with pembrolizumab (P) or atezolizumab (A) between 2015 and 2023. Pt characteristics such as age, sex, race, BMI, primary site (bladder vs upper tract UC (UTUC)), and antibiotic (Abx) use before or after start of ICI and pre-treatment platelet to lymphocyte (PLR) ratios (divided into quartiles) were collected. PrimRes was defined as pts who had clinical and/or radiologic PD or death from disease within 14 weeks (time period of 1 st assessment with imaging) of ICI initiation. Pts with PrimRes were compared to rest (responders, stable disease and subsequent PD). Multivariate cox regression models were used to identify factors associated with PrimRes. Results: Of the 335 pts, 129 (38.5%) pts had PrimRes based on our criteria. Median age was 73 yrs (35-95). PLR quartiles were clarified as (&lt;149, 149-207, 207-308, ≥308). In our multivariate regression model, we found that pts with PLR ≥308 had a significantly higher chance of PrimRes compared to those with PLR &lt;149 (Hazard Ratio (HR): 2.49; 95% CI: 1.22-5.15; p = 0.0133). Being underweight (BMI &lt; 18.5) was associated with significantly higher rates of PrimRes than normal weight pts (HR: 6.91; 95% CI: 1.55-48.81; p = 0.0211). Abx use within 60 days post ICI start (HR: 2.29; 95% CI: 1.38-3.83; p = 0.0015) and UTUC (HR: 0.46; 95% CI: 0.25-0.83; p = 0.0099) were associated with PrimRes to ICI. Conclusions: In our large cohort of pts with mUC receiving ICI, we report that PLR ≥308, BMI &lt; 18.5, use of Abx within 60 days post- ICI, and UTUC were associated with development of PrimRes to ICI. Ongoing genomic and immune correlates from tissues collected from our cohort will help us better understand the mechanisms of PrimRes to ICI. Validation and harmonization with more datasets and prospective studies can inform future steps towards patient-directed approaches. [Table: see text]
Effect of type of antibiotics (Abx) on outcomes with immune checkpoint inhibitors (ICIs) in patients (pts) with metastatic urothelial carcinoma (mUC) in a real-world setting.
Authors: Charbel Hobeika, Scott Dawsey, Ubenthira Patgunarajah, David Lynn, Nikhil Pramod, Wei Wei, Monica Nair, Kimberly Maroli, Allison Martin, Moshe Chaim Ornstein, Christopher Eing Wee, Timothy D. Gilligan, Amanda Nizam, Amanda Bonham, Omar Y. Mian, Paul G. Pavicic, C. Marcela Diaz-Montero, Shilpa Gupta
Journal: Journal of Clinical Oncology (2024)

640 Background: Use of Abx was associated with worse overall survival (OS) and progression-free survival (PFS) in our real-world cohort of mUC pts treated with ICI. (ASCO 2023). We now report the effect of type of Abx on ICI outcomes. Methods: In our cohort of 335 pts with mUC treated with ≥2 cycles of ICI with atezolizumab (A) or pembrolizumab (P) at CCF between 2015 and 2023, Abx class used in at least 20 pts was included. PFS and OS were calculated using Kaplan-Meier method, outcomes compared using log-rank testing and multivariate (MVA) Cox regression method. Results: Of 335 pts, 26.27% received A and 73.73% received P. Median follow-up was 26.8 mos. Details of type of Abx (cephalosporins (CPH), fluoroquinolones (FQ), penicillins (PCN) and trimethoprim-sulfamethoxazole (TMP-SMX), timing (30 or 60 (d) pre or post ICI start) and OS/PFS are shown in the Table. On MVA Cox regression analysis, Abx use within 60 (d) before ICI start was associated with worse OS (10.97 vs 16.03 mos.; (HR) 1.6 [1.2 -2.1], p=0.0004). Abx use within 30 (d) post ICI was associated with worse OS (6.9 vs 14.39 mos, p=0.008). Individual Abx and effect on OS and PFS are shown in Table. On MVA Cox regression analysis, Abx use within 60 (d) post ICI start was associated with worse PFS (3.12 vs 5.67 mos., HR 1.4; p=0.015). Conclusions: In our large cohort of pts with mUC treated with ICI, Abx PCN, CPH and FQ, within 30 and 60 (d) prior to starting ICIs demonstrated worse OS, Abx used after 30 and 60 (d) of ICI demonstrated worse OS and PFS, especially with CPH and PCN but not FQ. These findings have the potential to influence clinical practice, including using a higher threshold for prescribing antibiotics to pts with mUC when planned for or on ICI and the choice of Abx used. [Table: see text]