bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline bone pain as a prognostic marker for survival for men with metastatic hormone-sensitive prostate cancer (mHSPC): Patient-level analysis of SWOG 1216 trial.
Authors: Gebrael Georges , Jo Yeonjung , Swami Umang , Plets Melissa , Hage Chehade Chadi , Narang Arshit , Gupta Shilpa , Myint Zin , Sayegh Nicolas , Tangen Catherine , Hussain Maha H. A. , Dorff Tanya B. , Lara Primo N , Lerner Seth P. , Thompson Ian M. , Agarwal Neeraj
Published: January 2024

188

Background: Pain from bone metastasis significantly predicts overall survival (OS) in men with castration-resistant prostate cancer (PMID: 18487572). However, it has not been extensively evaluated in men with mHSPC. We hypothesized that baseline bone pain in men with mHSPC will be a significant prognostic marker for OS. Therefore, SWOG 1216 trial data which randomized men with mHSPC to androgen deprivation therapy (ADT) with orteronel vs bicalutamide was evaluated (PMID: 35446628,NCT01809691). Methods: Patient level data from SWOG 1216 were analyzed for those with documentation of baseline bone pain (yes or no). Patients were categorized into 2 cohorts: those with bone pain (BP1) vs those without bone pain (BP0). Progression-free survival (PFS) and OS were summarized by median with 95% confidence intervals (CI). Multivariable analyses on PFS and OS were done using Cox proportional hazard model, and were adjusted for treatment arm, disease burden, Gleason score, PSA (log base 2–transformed) and age (Table). All the analyses were done using R version 4.2.1. Results: Of the 1279 study participants: 301 men were in BP1 (23.5%) vs 896 were in BP0 (70.51%) cohort. Bone pain status was unavailable in 82 men (6.4%) men. Compared to BP0, BP1 cohort had lower median age (66 vs 68 years, p<0.01) and higher disease burden (70.4% vs 41.6%, p<0.001). Men in BP0 cohort had significantly better median PFS (3.7 vs. 1.3 yrs; p<0.001) and OS (NR vs 3.9 vs NR, p<0.001) then men in BP1 cohort. After adjustment for other prognostic variables including treatment, disease burden, Gleason score, log2PSA and age; bone pain was significantly associated with decreased PFS and OS (Table). Conclusions: Men with mHSPC with bone pain at baseline have worse survival outcomes despite treatment intensification and may be prioritized for enrollment in clinical trials. These data may aid patient counseling and warrant the inclusion of bone pain in the prognostic models of mHSPC. Clinical trial information: NCT01809691 . [Table: see text]
Preclinical characterization of human Kallikrein 2 (hK2) as a novel target for the treatment of prostate cancer.
Authors: Shen Fei , Kelly William Kevin , Pandit-Taskar Neeta , McDevitt Theresa , Smith Ryan , Menard Krista , Packman Kathryn , Chaudhary Ruchi , Rupnow Brent , Yu Margaret K. , Guckert Mary E. , Tian Shaozhou Ken , Chu Gerald , Xie Hong , Patricia Daniel , Max Steven I , Morris Michael J.
Published: January 2024

202

Background: Treatment options that are durably effective for patients with metastatic (m) castration-resistant prostate cancer (CRPC) remain limited despite available therapies, highlighting a continued unmet need for novel drug development. hK2 is overexpressed in prostate cancer (PC) and has little to no expression in non-prostate tissues. Here, we use a series of preclinical experiments to evaluate hK2 as a therapeutic target in PC. Methods: hK2 expression was assessed by immunohistochemistry (IHC) in non-metastatic (nm) castration sensitive PC (CSPC; n = 100), mCSPC (n = 98), and mCRPC (n = 45) samples obtained from tumor banks and warm autopsy tumor microarrays. Multiplex immunofluorescence (IF) was used to assess hK2 expression at different mCRPC tumor sites. hK2 cell surface expression in a human prostate cancer cell model (VCaP) and fresh mCRPC patient tumor samples was assessed by flow cytometry. hK2-targeting antibody internalization over time was visualized by confocal IF microscopy in VCaP cells. VCaP xenograft models in immune-compromised NSG mice were used to evaluate anti-tumor activity, defined as change in percent of tumor growth inhibition (ΔTGI), following treatment with 3 unique hK2-targeting experimental agents (Table). Whole-body planar and SPECT/CT imaging were used to assess hK2-targeting antibody tumor uptake in patients with mCRPC. Results: IHC confirmed robust hK2 expression across different PC stages with homogenous expression in nm/mCSPC and increased heterogeneity in mCRPC. Mean percent tumor staining of hK2 in mCRPC samples was 67.6% (bone), 65.7% (lymph nodes), and 33.5% (liver) by multiplex IF. Correlation of hK2 expression across mCRPC bony lesions (r = 0.74, p < 1.6e-06) was observed, suggesting intrapatient and interlesion homogeneity. Confocal microscopy demonstrated hK2 cell surface expression in VCaP cells, with rapid antibody internalization within 3 hours. Flow cytometry confirmed hK2 cell surface expression in both VCaP cells and mCRPC samples. Robust antitumor activity was observed following treatment with each hK2-targeting agent in the xenograft mouse model (Table). Whole-body and SPECT/CT scans confirmed accumulation of the hK2-targeting antibody to PC tumors in patients with mCRPC. Conclusions: hK2 expression was homogenous in nm/mCSPC, with increased heterogeneity in mCRPC. Antitumor activity was observed across hK2-targeting agents. These data demonstrate that therapeutic strategies targeting hK2 hold promise in PC treatment and support further investigation of these agents in clinical studies. [Table: see text]
Rate of hospitalization and length of hospital stay during and post docetaxel for darolutamide in metastatic hormone-sensitive prostate cancer using ARASENS.
Authors: Morgans Alicia K. , Boegemann Martin , Paracha Noman , Grossman Jamie , Rodriguez Santamaria Fernando , Tyas Emma , Candish Jane , Shore Neal D.
Published: January 2024

228

Background: ARASENS was a randomized, double-blind, Phase III trial of darolutamide (daro) + docetaxel + androgen deprivation therapy (ADT) vs. placebo (pbo) + docetaxel + ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC). We sought to compare rates of hospitalizations and length of hospital stay (LoS) per patient due to any reason, and due to adverse events (AE) during or post docetaxel using data from ARASENS. Methods: We used mixed effects negative binomial regression to estimate time-varying rate of hospitalization and LoS by patient. Patients with records that began on the same start date were considered duplicates and were condensed into one visit, using the latest end date. Patients with multiple records with overlapping time periods were combined into one visit. A constant hospitalization rate assumption was considered inappropriate since docetaxel is administered for 6-cycles (~4.14 months). Hospitalizations that began within and after first 4 months of treatment were grouped together. Conversely, LoS was assumed to be time invariant. Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalization both due to any reason and to AE (Table 1). Daro was associated with a numerical reduction in rate of hospitalization (per year) due to any reason during docetaxel (0.75 days [95% CI: 0.61, 0.88]) vs. pbo (0.91 days [95% CI: 0.75, 1.07]) and after docetaxel (0.31 days [95% CI: 0.26, 0.37]) vs. pbo (0.38 days [95% CI: 0.31, 0.45]). A similar trend was observed for hospitalizations due to AE. Daro was associated with a marginally longer LoS per hospitalization compared with pbo (+1.90 days). Similar results were seen for LoS due to AE (+1.67 days). Conclusions: Daro was associated with a numerically lower rate of hospitalization, but marginally longer LoS compared to pbo. A lower rate of hospitalization was observed post docetaxel as opposed to during docetaxel. Clinical trial information: NCT102799602 . [Table: see text]
Individual-level social determinants of health and allostatic load/chronic toxic stress in men with prostate cancer.
Authors: Stabellini Nickolas , Cullen Jennifer , Bittencourt Marcio S , Moore Justin , Weintraub Neal L , Datta Biplab , Coughlin Steven S. , Shanahan John , Montero Alberto J. , Guha Avirup
Published: January 2024

263

Background: Allostatic load (AL)/chronic toxic stress is linked to a higher risk of adverse cancer-specific and cardiac events in prostate cancer (PC) patients especially non-Hispanic Blacks (NHBs). We hypothesize that NHBs experience more adverse social determinants of health (SDOH) that increases this AL. Methods: We included men≥18 years diagnosed with PC (2010-2022). Individual-level SDOH with 19 covariates across 4 domains was obtained. Pre-PC diagnosis AL was calculated as an ordinal measure (0-11). Components and cutoffs for the AL score: Each measure above the cutoff add 1 point to AL. Systolic blood pressure (BP) ≥140 mmHg, diastolic BP ≥90 mmHg, heart rate >100 bpm, total cholesterol (chol) ≥240 mg/dl, high-density lipoprotein chol ≤50 mg/dl, triglycerides ≥150 mg/dl, glycated hemoglobin ≥6.5, body mass index ≥30 kg/m2, glucose ≥110 mg/dl, C-reactive protein >3 mg/L and interleukin-6 >1.8 pg/ml. A gradient-boosting Machine Learning model ranked AL predictors using SHAP scores (SS). Cubic splined from logistic regressions defined SDOH adversity cutoffs. Results: Among 4,258 patients (886 NHB), the median age was 69 (IQR 63-77). Most were former smokers (44.2%), and the median Charlson comorbidity score was 4 (IQR 2-7). In NHBs, the SDOH variables among the top 5 overall predictors of AL were annual income (SS=0.10), neighborhood murder index (SS=0.07), neighborhood median income (SS=0.06), and neighborhood car theft index (SS=0.05). Considering all the SDOH features analyzed, NHBs faced adversity in 12 of 19 SDOH features (63%; Table). Conclusions: SDOH related to the neighborhood, built environment, and economic stability, are crucial predictors of pre-PC diagnosis AL in NHBs. [Table: see text]
Prostate Cancer Foundation (PCF) screening guidelines for prostate cancer in Black men in the United States.
Authors: Garraway Isla , Carlsson Sigrid V. , Nyame Yaw A. , Vassey Jason , Chilov Marina , Fleming Mark T. , Frencher Stanley K , George Daniel J. , Kibel Adam S. , King Sherita A , Kittles Rick , Mahal Brandon A , Pettaway Curtis Alvin , Rebbeck Timothy , Rose Brent S. , Vince Randy , Winn Robert A. , Yamoah Kosj , Oh William K.
Published: January 2024

264

Background: Black men in the United States are considered a high-risk population for being diagnosed with and dying from prostate cancer. Few guidelines have outlined specific recommendations for prostate-specific antigen (PSA)-based prostate cancer screening among Black men. We performed a comprehensive literature search and assembled a diverse, interdisciplinary panel of experts to establish practical consensus guidelines addressing PSA screening in Black men. Methods: A comprehensive literature search was conducted in April 2023 in PubMed and Embase. A total of 287 studies were reviewed utilizing Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Of these, 265 were relevant. The panel’s expertise included fields of primary care, urology, medical and radiation oncology, translational science, and patient advocates. Results: Six guideline statements were developed. Three randomized controlled trials provided Level 1 evidence that regular PSA screening of men aged 50-74 of average risk reduces metastasis and prostate cancer death at 16-22 years. The best available evidence for Black men, who are considered higher than average risk for prostate cancer metastasis and death, comes from observational (Level 3) and modeling (Level 4) studies that consider the age to obtain a baseline PSA, the frequency of testing, and the age when screening should end. Cohort studies suggest that discussions with health care providers about baseline PSA testing should begin by the time Black men are in their early 40s and modeling data suggests prostate cancer develops 3-9 years earlier in Black men compared to their peers. Lowering the age for baseline PSA testing from 50-55 years to 40-45, followed by regular screening intervals until the age of 70 (when to stop is determined by age, PSA values, and health factors) would reduce prostate cancer mortality in Black men (~30% relative reduction) without significantly increasing the rate of overdiagnosis. Conclusions: Black men should obtain information about PSA screening for prostate cancer. Among Black men who elect screening, baseline PSA testing should occur between ages 40-45. Depending on the PSA value and health status, annual screening should be strongly considered. Personalized prostate cancer surveillance and/or treatment can prevent potential harms from overdiagnosis.
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: Gartrell Benjamin Adam , Phalguni Angaja , Mundle Suneel , McCarthy Sharon , Brookman-May Sabine D. , De Solda Francesco , Jain Ruhee , Ploussard Guillaume , Hadaschik Boris A.
Published: January 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<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]
Selection of active surveillance in Medicaid patients: Results from the Michigan Urological Surgery Improvement Collaborative.
Authors: Srivastava Arnav , Daignault-Newton Stephanie , Meah Sabir , Faraj Kassem S , Ginsburg Kevin , Goh Keow , Hollenbeck Brent K. , Shahinian Vahakn , Herrel Lindsey A. , Borza Tudor
Published: January 2024

302

Background: Active surveillance (AS) is the preferred treatment for low-risk prostate cancer. Insurance coverage and cost sharing often influence treatment choices for providers and patients. The impact of insurance payer, specifically Medicaid, on treatment selection in prostate cancer remains understudied. Methods: We identified patients with biopsy-proven prostate cancer from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry, a statewide quality improvement collaborative, from 2016-2021. We captured risk category, insurance payer (Medicaid vs. private insurance), and treatment (AS vs. primary treatment). Watchful waiting rates were under 2% in both payer groups; these patients were excluded from analysis. We used logistic regression to assess the correlation between payer status and treatment choice by prostate cancer risk group. Results: We identified 38,663 patients. Most patients had private insurance (51%), followed by Medicare (45%) and Medicaid (3%). Median age was 62 (IQR 58 – 66) for privately insured patients and 60 (IQR 56 – 63) for Medicaid patients. Among patients with low-risk disease, 65% of privately insured patients and 67% of Medicaid patients elected for AS. AS for favorable intermediate-risk prostate cancer was also similar across the payer groups (private 20%, Medicaid 19%). In an adjusted analysis Medicaid and privately insured patients did not demonstrate different odds of AS (OR 0.99 (95%CI 0.71 – 1.40), p > 0.9). No significant differences in treatment selection were noted in favorable or unfavorable intermediate-risk patients (Table). Conclusions: Our analysis, from a granular statewide registry, suggests that Medicaid patients undergo similar treatment patterns to commercially insured patients. This suggests that insurance status may not drive AS selection in our cohort. Our work points towards not only the increased adoption of AS, but also its adoption across payers. [Table: see text]
Clinical and patient-reported outcomes of fully adaptive MR-guided stereotactic radiotherapy to prostate: Real-world experience from the UK.
Authors: Das Prantik , Nugent Killian , Dallas Nicola Louise , Perna Carla , Sabharwal Ami , Ford Daniel , Camilleri Philip
Published: January 2024

303

Background: Stereotactic MR-guided adaptive radiotherapy (SMART) brings several advancements including enhanced soft tissue definition, adaptation of individual fractions based on daily anatomy, real time tracking of prostate coupled with beam gating that prevents treatment delivery if the prostate is outside the treatment boundary and negating the need for invasive fiducial markers. Here we evaluate treatment response and acute and intermediate patient adverse events amongst prostate cancer patients who underwent SMART. Methods: A total of 197 patients with localised prostate cancer were treated with SMART. Patients were assessed for eligibility against robust institutional criteria. SMART consisted of MR- and computed tomography (CT) simulation scan, inverse intensity-modulated radiotherapy (IMRT) treatment planning and daily plan re-optimization prior to treatment delivery with editing CTVs (as per daily variation) and OAR recontouring within the first 3 cm outside the PTV. Prescription dose was 36.25 Gy in 5 fractions delivered on alternate days. Patients who completed a baseline 12 item PRO-CTC AE, before treatment, were subsequently followed up with the same graded questionnaire at set time points. Results: Median follow up was 12 months (inter quartile range 6 – 36). Patients included low (6%), intermediate (86%) and high risk (8%). Median pre-treatment PSA was 7.09 ng/ml (interquartile range IQR 1 – 133.2). At first follow up at 6 months, median drop in PSA was 97.09 % from base line (range 27.7– 99.9 %, SD 15.04). At second follow up at 12 months, median change in PSA was 96.92% (range 5.88– 233.3%, SD 12.41). At 24 months median PSA was 0.28 ng/ml (IQR 0.03 -3.26) with a median drop from baseline of 95.98%. ADT was used in 88% of patients and median duration of ADT was 6 months (IQR 3-30). 69 patients, who completed baseline and subsequent PRO CTC AE questionnaires in different time frames were included in analysis. More than 80% of men reported no change from baseline urinary toxicity during follow up apart from urinary urgency. Regarding GI toxicities, new ≥ frequent/severe patient reported adverse events were diarrhoea (9%), constipation (3%) and pain on opening bowels (6%) in the first 3 months but were all absent after 33 months. No patient reported frequent GI bleeding. No grade ≥4 toxicity was seen. Conclusions: SMART shows low acute and intermediate toxicities and excellent short-term outcomes.
Impact of a rash management guide on incidence and severity of rash with apalutamide: Experience from the Apa-RP study in high-risk localized prostate cancer.
Authors: Shore Neal D. , Hafron Jason , Saltzstein Daniel , Bhaumik Amitabha , Aggarwal Pankaj , Potdar Rushikesh , Phillips Jennifer , McGowan Tracy
Published: January 2024

316

Background: Apa-RP is a multicenter, open-label, single-arm Phase 2 study of adjuvant treatment with apalutamide and androgen deprivation therapy (ADT) in treatment-naïve patients with high-risk localized prostate cancer who underwent radical prostatectomy (NCT04523207). A rash management guide was implemented to improve dermatologic adverse events (AEs) that included proactive patient education on appropriate skin care and monitoring for rash, and frequent outreach through patient phone calls. We present rash-related safety data from Apa-RP compared with data from 2 Phase 3 apalutamide registrational studies. Methods: 108 patients were treated with apalutamide 240 mg once daily with ADT for 12 28-day cycles. Rash occurrence was monitored and skin-related AEs were defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading scale. These factors were collated and compared with data from the North American population from SPARTAN (non-metastatic castration-resistant prostate cancer; NCT01946204) and TITAN (metastatic castration-sensitive prostate cancer; NCT02489318). Results: Of 108 patients in Apa-RP, 21.3% developed rash vs 28.3% in SPARTAN and 33.3% in TITAN. Information on rash severity, median time to onset of first rash, the proportion of patients with rash resolution, median time to resolution and the treatment administered for rash are provided in the Table. Conclusions: The Apa-RP rash management protocol demonstrates a proactive and patient-empowered approach to monitoring and managing patients on apalutamide who develop skin rash. With increased vigilance from the care team and appropriate patient education, it may be possible to reduce the incidence, severity and median time to resolution of skin rash. Clinical trial information: NCT04523207 . [Table: see text]
Every-other-day or once-a-week: Long-term efficacy outcomes of the multicenter randomised PATRIOT prostate SBRT trial.
Authors: Ong Wee Loon , Quon Harvey Charles , Ong Aldrich , Cheung Patrick , Chu William , Chung Hans T. , Vesprini Danny , Chowdhury Amit , Panjwani Dilip , Alayed Yasir , Pang Geordi , Korol Renee , Davidson Melanie , Ravi Ananth , McCurdy Boyd , Zhang Liying , Kulasingham-Poon Meghan , Mamedov Alexandre , Deabreu Andrea , Loblaw Andrew
Published: January 2024

325

Background: We aim to report the long-term efficacy outcomes of the PATRIOT trial, a multicenter phase 2 randomised trial of every-other-day (EOD) versus once-a-week (QW) schedule for stereotactic body radiotherapy (SBRT) for prostate cancer (NCT01423474). Methods: Between January 2012 and November 2013, 152 men with low to intermediate risk prostate cancer were randomised to prostate SBRT 40Gy in 5 fractions, delivered EOD (n=75) or QW (n=77). The oncological outcomes evaluated were biochemical failure (BF) (based on Phoenix criteria), metastases free survival (MFS), prostate cancer specific survival (PCSS) and overall survival (OS). Time-to-event was estimated from the start date of SBRT to event of interest or last follow-up. The cumulative incidence of BF was estimated using the Nelson Aalen estimates, while MFS, PCSS and OS were estimated using the Kaplan Meier method. Results: The median follow-up for the cohort was 91 months (IQR: 61-116 months). Five men in the EOD arm and eight men in the QW arm developed BF. The 8-year cumulative incidence of BF were 5.5% (SE=0.03) in the EOD arm and 9.6% (SE=0.04) in the QW arm (P=0.3). None of the men in the EOD arm developed metastases, while three men in the QW arm did. The 8-year MFS were 100% in the EOD arm and 95.9% (95%CI=91.4-100%) in the QW arm (P=0.08). Thirteen men had died at last follow-up, of which two were prostate cancer specific death. The 8-year PCSS were 100% in the EOD arm and 97.2% (95%CI=93.5-100%) in the QW arm (P=0.3), while the 8-year OS were 96.0% (95%CI=91.7-100%) in the EOD arm and 85.4% (95%CI=76.4-95.5%) in the QW arm (P=0.3). Conclusions: There are no statistically significant differences in long-term oncological outcomes between EOD and QW for five-fraction prostate SBRT in the PATRIOT trial. However, the trial was powered for acute toxicity differences, and not MFS or OS. Either prostate SBRT schedule could be safely delivered depending on patients’ preference, or for logistic reasons. We plan to combine these data with the Swiss EOD vs QW randomised trial (NCT01764646) to improve the power to detect these important outcomes. Clinical trial information: NCT01423474 .
Neoadjuvant pamiparib plus abiraterone and ADT for high-risk/very high-risk localized prostate cancer: Results of a prospective study.
Authors: Zhuang Junlong , Zhang Shun , Qiu Xuefeng , Zhou Feng , Guo Hongqian
Published: January 2024

327

Background: Androgen receptor (AR) signaling inhibition increases genomic instability of double-stranded DNA breaks, and co-inhibition of AR and PARP induces synthetic lethality in multiple preclinical models. In this study we tested the efficacy and safety of neoadjuvant pamiparib plus abiraterone and ADT in HRLPC/VHRLPC before radical prostatectomy (RP). Methods: In this phase II single-arm neoadjuvant trial, patients with HRLPC/VHRLPC (defined as Gleason ≥ 8 and/or cT3-4N0-1 and/or PSA≥ 20 ng/mL) were enrolled to evaluate the safety and antitumor efficacy of pamiparib before prostatectomy. Patients received pamiparib plus abiraterone and ADT for 4 months followed by prostatectomy. The primary objective was the rate of pathological complete response (pCR) or minimal residual disease (MRD). MRD was defined as ≤0.5cm of tumor or residual cancer burden ≤0.25 cm3 (RCB = tumor volume x cellularity). Secondary endpoints include PSA response, surgical staging at RP, the rate of PSA recurrence 12 months after surgery, and safety. Results: A total of 30 pts were enrolled, 29 pts (HRRm n=7) completed the full course of study treatment and underwent RP. One patient declined surgery for personal reasons and received further systemic therapy. The median age was 66 (range 41-77). Clinical characteristics were typical of high-risk disease: median PSA 34.4 ng/ml (range 10.8-204) and clinical stage cT3 (n=27), Gleason 8-10 (n=20),9 pts had enlarged pelvic lymph nodes. Following 4 months of therapy, the median pre-RP PSA was 0.103 ng/ml (range 0.006 -1.1). Final pathologic results showed that 8 pts (27.5%) achieved pCR or MRD, 3 pts (10.3%) achieved pCR, 5 patients (17.2%) achieved MRD, and 18 patients (62%) had staging downgrades, with no patients experiencing progression. Compared to patients with an HRR wild type (HRRwt), those with HRR mutations had no difference in pCR or MRD. The margin positivity rate was 6.8%(n=2) in 29 pts, all of whom were T3 stage patients. No Grade 3/4 drug-related adverse event was observed. The most common 1-2 adverse event were anaemia (48.2%), AST/ALT increased (34.4%) and hypertriglyceridemia (44.8%). Conclusions: Neoadjuvant therapy of pamiparib plus abiraterone and ADT for 4 months was effective and safe in pts with HRLPC/VHRLPC. Clinical trial information: NCT05376722 .
Temporal and regional patterns of prostate cancer positron emission tomography imaging among commercial insurance beneficiaries in the United States.
Authors: Leapman Michael , Long Jessica B. , Westvold Sarah J. , Rabil Maximilian , Sprenkle Preston , Kim Isaac Yi , Saperstein Lawrence , Fallah Jaleh , Suzman Daniel L. , Lerro Catherine , Xu Jianjin , Kluetz Paul Gustav , Karnes R. Jeffrey , Kunst Natalia , Wang Shi-Yi , Ma Xiaomei , Gross Cary Philip
Published: January 2024

34

Background: Prostate specific membrane antigen positron emission tomography (PSMA-PET) imaging improves prostate cancer visualization and has been proposed as a tool to guide treatment decisions. As PSMA-PET imaging agents were not approved in the United States (US) until December 2020, little is known about national patterns of PET imaging utilization. Methods: We conducted a dynamic cohort study to evaluate use of PET imaging among insurance beneficiaries aged 40-89 years with a diagnosis of prostate cancer using deidentified administrative claims from Blue Cross Blue Shield Axis. We calculated the proportions of patients undergoing PET imaging in semiannual periods from January 1, 2016, through December 31, 2022, examining tracers specific to prostate cancer, including PSMA-targeted agents as well as fluciclovine, sodium fluoride, and choline tracers. Cochran-Armitage tests were used to evaluate trends in the proportion of individuals receiving PET imaging over time. We also assessed the association between regional [hospital referral region (HRR)] level contextual sociodemographic and healthcare characteristics and regional use of PSMA-PET imaging in 2022 using chi-square tests. Results: There were 410,505 beneficiaries with prostate cancer identified in the study period. The semiannual proportion of patients undergoing PET imaging increased from 4.5 [(95% confidence interval (CI) 4.1-5.0] per 1,000 in the first half of 2016 to 41.7 (95% CI 40.6-42.9) per 1,000 in the second half of 2022, p<0.001. Increases in PET imaging were driven by uptake of PSMA-PET imaging, which increased from 0.7 (95% CI 0.6-0.9) per 1000 in the second half of 2021 to 37.5 (95% CI 36.4-38.6) per 1,000 in the second half of 2022, p<0.001. Following approvals of PSMA-PET agents, other forms of PET imaging rapidly decreased – from 18.2 (95% CI 17.4-18.9) per 1000 in the second half of 2021 to 4.6 (95% CI 4.3-5.0) per 1,000 in the same period of 2022, p<0.001. Compared to HRRs in quartile 1 (Q1), HRRs in Q4 of PSMA-PET use in 2022 had higher levels of education (25.0% with college education or higher in Q1 versus 29.4% in Q4, p=0.005) and median household income ($50,200 in Q1 versus $60,900 in Q4, p<0.001). Conclusions: In this study from a large commercial US health insurer, PSMA-PET was rapidly incorporated into clinical practice and is now the dominant prostate cancer radiotracer. However, the initial uptake of PSMA-PET may be accompanied by disparity, as our data suggests less use in areas with lower income and education measures.
A randomized phase II trial of neoadjuvant chemokine modulation in patients with localized prostate cancer undergoing radical prostatectomy.
Authors: Jatwani Karan , Kalathil Suresh , Slomba Ronald , Farmer Bailey , Attwood Kristopher , Roy Arya Mariam , Singh Prashant , Kauffman Eric , Gopalakrishnan Dharmesh , George Saby , Levine Ellis Glenn , Guru Khurshid , Kalinski Pawel , Chatta Gurkamal S.
Published: January 2024

340

Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). A high intra-tumoral CD8+ T lymphocyte density is associated with improved survival post-RP,1 suggesting possible clinical benefit from neoadjuvant chemokine modulation (CKM).2,3 We present the interim results of a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP were randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (Arm A: rintatolimod + aspirin + IFN-α: “Complete CKM regimen”) vs CKM doublet (Arm B: rintatolimod + aspirin) vs no CKM (Arm C). Methods: Thirty patients (10 per arm) are to be enrolled to assess CD8+ T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations represent secondary endpoints. Correlative blood studies analyzed the pre- vs post-CKM changes in Granzyme B (GrB; marker of effector/cytotoxic function in CD8+ T cells and FoxP3 (Treg marker) in CD4+ T cells. Results: The trial has enrolled 11 patients thus far (N=5 Arm A, 3 Arm B, 3 Arm C). There were no clinicopathological differences between the groups. Eight patients (on Arms A and B) were analyzed for changes in cytotoxic T cell numbers (CTL-D: GrB+CD8+ T-cells) in the blood. In Arm A, the mean pre-CKM CTL-D was 35.5% (±23.2%) and post-CKM was 47.7% (± 32.5%), while in Arm B, respectively, 37.9% (±22.2%) vs 37.1% (± 21.6%). These changes were reflected in the increased CTL/Treg markers in the post-treatment samples of patients on Arm A. These data indicate the ability of the “complete CKM regimen” (Arm A) to selectively enhance the CTL effector function in circulating CD8+ T cells, without enhancing the Treg markers. CKM regimen was well tolerated with no Grade 3 or above adverse events (AEs). Conclusions: In this interim analysis, treatment in all arms was feasible and safe. CTL-D and CTL-D/Treg in Arm A (“complete CKM”) shows an increasing trend over the course of CKM treatment. The levels of CTL-D in the resected prostate tissues are being currently evaluated. The study continues recruiting patients. 1. Yang, Y et al (PMID 33085799). 2. Muthuswamy, R et al (PMID 27199259). 3. Theodoraki, MN et al (PMID 29853604). Clinical trial information: NCT03899987 .
Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial.
Authors: Bourlon Maria Teresa , Escudier Bernard , Burotto Mauricio , Powles Thomas , Apolo Andrea B. , Shah Amishi Yogesh , Porta Camillo , Suárez Cristina , Barrios Carlos H. , Richardet Martin , Gurney Howard , Kessler Elizabeth R. , Tomita Yoshihiko , Bedke Jens , Wang Fong , Wang Peter , Panzica Julie , Fedorov Viktor , Motzer Robert J. , Choueiri Toni K.
Published: January 2024

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Background: N+C demonstrated superior progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in patients (pts) with previously untreated aRCC in the primary analysis of the phase 3 CheckMate 9ER trial (18.1 mo median follow-up). N+C maintained efficacy benefits vs S with 44.0 mo median follow-up. Here, we report updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety with extended follow-up. Methods: Pts with aRCC were randomized to N 240 mg every 2 weeks + C 40 mg QD vs S 50 mg QD (4 weeks of 6-week cycles) until disease progression or unacceptable toxicity, with up to 2 y of N. The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Overall, 323 pts were randomized to N+C and 328 to S (ITT). With 55.6 mo median (48.1 mo min.) follow-up for OS, median PFS was 16.4 vs 8.4 mo (hazard ratio [HR] 0.58, 95% CI 0.49-0.70) and median OS was 46.5 vs 36.0 mo (HR 0.77, 95% CI 0.63-0.95) with N+C vs S. ORR (95% CI) was 55.7% (50.1-61.2) vs 27.7% (23.0-32.9); 13.6% vs 4.6% of pts achieved complete response (CR); 6.5% vs 13.7% had progressive disease (PD), respectively. Median (range) time to response (TTR) was 2.8 (1.0-22.2) vs 4.3 (1.7-30.4) mo for N+C vs S, and median (95% CI) duration of response (DOR) was 22.0 (18.0-25.2) vs 15.2 (10.9-19.3) mo. Efficacy by IMDC favorable (FAV) and intermediate/poor (I/P) risk groups is reported in the Table. Among all treated pts (320 pts each arm), any-grade (grade ≥ 3) treatment-related adverse events (TRAEs) occurred in 97.5% (67.5%) vs 93.1% (55.3%) with N+C vs S. Any-grade TRAEs led to discontinuation of N or C in 28.1% of pts (N only, 10.0%; C only, 10.3%; N+C simultaneously, 6.6%; N+C sequentially, 1.3%) and of S in 10.9% of pts. Additional analyses in subgroups of clinical interest will be presented. Conclusions: With 55.6 mo median follow-up, N+C continues to maintain meaningful long-term efficacy benefits over S. No new safety concerns were identified. These results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . [Table: see text]
Disparities in uptake of new FDA-approved therapies for metastatic clear cell renal cell carcinoma.
Authors: Hayes Mitch , Buhlmann Melanie , Gore L. Robert , Zemp Logan , Spiess Philippe E. , Manley Brandon J. , Jim Heather S.L. , Chahoud Jad
Published: January 2024

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Background: Multiple new therapies for metastatic clear cell renal cell carcinoma (mccRCC) have been approved in the past decade. Real-world (RW) data on access to novel therapies and the impact on health-related disparities are limited. This study assessed RW access to novel therapies along with racial and social disparities for mccRCC patients and their impact on clinical outcomes. Methods: The longitudinal Flatiron Health database was queried for adult patients with mccRCC who received systemic treatments from Jan 2011 to Dec 2022 with at least two documented clinical visits. Patients < 45 years old were excluded. Data was collected on age, gender, race, ethnicity, ECOG status, practice type, stage, smoking status, socioeconomic status (SES) defined by the Yost index, insurance status, overall survival (OS), and the first 14 treatments received. Patients were categorized as receiving a novel therapy if they received a first line mccRCC regimen during prespecified time windows starting on their first-line FDA approval date until 6 months later or when the next novel drug was approved, whichever date came later. Chi square test was used to assess variables across race. Univariable Cox proportional hazard models were used for OS analysis. R version 4.3.0 was used for programming. Results: 7,113 patients were included. 68.8% of the cohort was white, 7.1% Black, 1.4% Asian, 12.7% other, and 10.1% missing. Advanced age and receiving care in a community practice setting were associated with worse OS (CI 1.45-1.81 and CI 0.70-0.81, respectively), while SES was not (CI 0.81-1.01 for highest vs lowest group). Black race was associated with a 24% increased hazard of mortality compared to white race (CI 1.11-1.39, p=0.0003), and this was more pronounced in patients <65 years old (CI 1.17-1.63, p=0.0001). 31.4% of patients received at least one novel therapy during the study period, and there were no differences by race. Receipt of novel therapy was not statistically associated with improved OS (p=0.1660). Conclusions: This is the first study in the immunotherapy era to highlight the worse OS of Black patients with mccRCC. Access to care at an academic center was associated with improved OS. Access to novel therapies did not differ between racial groups in the US using RW data. [Table: see text]
Baseline CD8 lymph node avidity with 89-Zr-crefmirlimab in patients with metastatic renal cell carcinoma and response to IO therapy.
Authors: Zang Peter D. , Twardowski Przemyslaw , Chen Delphine L , Hall Evan Thomas , Hays David , Wilson Ian , Schmiedehausen Kristin , Ferris Michael , Le William , Postow Michael A. , Pal Sumanta Kumar
Published: January 2024

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Background: Prior studies with crefmirlimab, a 89-Zr labeled antibody with specificity for CD8+ cells, have shown a strong correlation with SUV uptake and IHC of the same lesions validating its use (Pal 2023). We predicted that responders to IO therapy would have higher CD8 lymph node avidity than non-responders. Methods: Pts enrolled had a diagnosis of mRCC and must have received IO therapy (CPI/TKI, CPI/CPI, or CPI monotherapy). Pts obtained a crefmirlimab PET/CT within 1 week before CPI infusion as baseline. PET intensity was determined using SUVMax, SUVMean, SUVPeak. Highly avid lymph nodes (SUVMax > 10) were quantified. Best overall response was determined using RECIST 1.1 criteria with SUV values and number of CD8 PET-avid lymph nodes compared using a Wilcoxon Signed Rank test in R. Results: A total of 17 pts (9 M: 8 F) were enrolled across 3 sites with 9 pts locally available for analysis. The median age of pts was 64 years old (54-71). Histology types included 12 clear cell (71%), 2 papillary (12%), and 3 indeterminate (17%). There were 3 responders (18%), 12 non-responders (71%), and 2 non-evaluable (12%). The most common treatment regimens patients received in descending order were cabozantinib + nivolumab (44.44%), nivolumab (33.33%), and ipilimumab + nivolumab (22.22%). Strong correlation was observed between CD8 cell density and SUVMean (p <0.0003 by Spearman’s correlation). The average number of CD8 PET-avid lymph nodes (defined as SUVMax > 10) in responders was 6 versus 1.17 in non-responders (p = 0.025, 95% CI [1.99,7]). SUVMax, SUVMean, SUVPeak across all CD8 PET-avid lymph nodes for responders were 15.58, 12.63, 11.44 and for non-responders were 9.86, 8.53, 7.79 respectively. The difference between SUVMax, SUVMean, SUVPeak values reached statistical significance for all three values (p = 0.023 95% CI [3.42,7.84], p = 0.023 95% CI [2.64,5.84], p = 0.029 95% CI [1.18, 5.41] respectively). Conclusions: Our results show that pts with higher number of CD8 PET-avid lymph nodes at baseline was associated with better response to IO therapy; responders also had overall higher SUV uptake in CD8 PET-avid lymph nodes than non-responders. Our findings suggest that those with a more enriched CD8 phenotype trended towards better outcomes and may be a reliable predictor for IO therapy response. Clinical trial information: NCT03802123 .
Mayo Adhesive Probability score to predict renal function following partial nephrectomy.
Authors: Nicaise Edouard , Schmeusser Benjamin , Shah Yash , Futral Cameron , Ambadi Sriram , Imtiaz Nahar , Patil Dattatraya H. , Ogan Kenneth , Master Viraj A.
Published: January 2024

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Background: Mayo Adhesive Probability (MAP) score, which measures adherent perinephric fat in renal cell carcinoma (RCC), is associated with surgical complexity and cancer progression in patients undergoing partial nephrectomy (PN). PN carries perioperative risk but preserves renal function versus radical nephrectomy (RN). We analyzed whether MAP score can predict long-term postoperative renal function in localized RCC patients who underwent PN. Methods: We reviewed our nephrectomy database to identify pT1-T3a RCC patients who underwent PN. Patients with metastatic disease, IVC thrombus, multiple masses, and prior nephrectomy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI 2021 formula and patients with values <15mL/min/1.73m2 were excluded. We calculated MAP scores from preoperative cross-sectional imaging and dichotomized patients into low (1-3) versus high (4-5) cohorts. Continuous and categorical outcomes were compared using ANOVA and chi-square tests. A hierarchical generalized linear mixed effect model was used to evaluate predictors of long-term, postoperative eGFR following PN. Results: 314 patients were identified and 97 (30.9%) were classified with a high MAP score. These patients were older (64.5 vs. 58.3 years, p<0.001), more often male (85.6% vs. 52.5%, p<0.001), and white (79.4% vs. 67.7%, p=0.016). MAP score was associated with obesity (59.8% vs. 42.9%, p=0.006), diabetes (36.1% vs. 22.6%, p=0.013), hypertension (82.5% vs. 63.1%, p<0.001), and severe CCI (5+; 35.1% vs. 23.5%, p<0.001). No difference was observed in the rate of current or former smokers. Final tumor size was greater among patients with high MAP (4.1 vs. 3.4cm, p<0.001) but no difference was noted in pT stage. Rate of acute renal failure postoperatively (dialysis or eGFR <15 within 30 days) was similar between the two cohorts (1% vs. 1.4%, p=0.797). The tablepresents the model used to evaluate postoperative eGFR predictors. Conclusions: High MAP score predicts a greater eGFR decline following PN for localized RCC. Considering the risks of PN, MAP scoring may indicate surgical complexity and inform shared decision-making when considering nephron-sparing surgery for RCC. [Table: see text]
Venous tumor thrombus destinations in patients with renal cell carcinoma.
Authors: Nabavizadeh Reza , Pessoa Rodrigo , Cheville John , Lohse Christine M. , Costello Brian Addis , Lucien Fabrice , Thompson Houston R. , Boorjian Stephen A. , Leibovich Bradley C. , Sharma Vidit
Published: January 2024

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Background: Venous tumor thrombus (VTT) is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). It is unknown if VTT and pulmonary embolism (PE) predispose patients to pulmonary metastasis. Methods: We queried our institutional registry for ccRCC patients undergoing radical nephrectomy (1970-2019). Cox proportional hazards regression models, adjusting for factors associated with ccRCC progression, were used to determine if VTT and PE were associated with pulmonary metastasis. Results: Of 3,410 patients studied, 1,025 (30%) had VTT, and patients with VTT were more likely to present with pulmonary metastasis at nephrectomy (20% vs 7%, p<0.001). Within the VTT subset, level of VTT was not significantly associated with pulmonary metastasis at nephrectomy (p=0.3). For all patients who had metastatic disease at nephrectomy (n=643), pulmonary metastasis was more common in those with VTT versus those without VTT (68% vs 51%, p<0.001). Excluding patients with pulmonary metastasis at nephrectomy, on multivariable analysis, VTT remained associated with post-nephrectomy pulmonary metastasis (hazard ratio (HR) 1.31, p<0.001) without a notable difference in HRs between renal vein (1.27) and caval (1.38) VTT. Presence of PE in the setting of VTT was associated with increased pulmonary metastasis post-nephrectomy (HR 2.31, p<0.001). Conclusions: VTT is associated with disproportionately increased pulmonary metastasis at presentation and post-nephrectomy in ccRCC patients. Further, the presence of PE at nephrectomy for VTT was associated with increased pulmonary metastasis post-nephrectomy. These results support a metastatic predilection of ccRCC with VTT to the lungs.
Real-world outcomes of patients with operable renal cell carcinoma from the German translational cancer research consortium (DKTK) network.
Authors: Grünwald Viktor , Thomas Christian , De Santis Maria , Gratzke Christian , Chun Felix , Mager Rene , Retz Margitta , Von Amsberg Gunhild , Ivanyi Philipp , Christian Bolenz , Kübler Hubert , Hadaschik Boris A. , Hahn Svenja , Erhard Ian , Reiter Bastian , Lablans Martin , Vehreschild Janne , Brucker Daniel , Maier Daniel
Published: January 2024

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Background: Nephrectomy and risk-adapted adjuvant pembrolizumab are standard treatments in localized renal cell carcinoma (RCC). Risk of recurrence from clinical trials is utilized to council patients. However, recurrence and survival in real-world practice may differ. We report real-world outcome data of patients with RCC from the German Cancer Consortium’s Clinical Communication Platform, a federated data warehouse infrastructure for oncological real-world evidence. Methods: Adult patients from routine care and nephron sparing surgery (NSS) or nephrectomy (Nx) for non-metastatic RCC between 2013-2022 at tertiary German cancer centers were retrospectively analyzed. Clear cell (cc), papillary (p) or NOS histologies were eligible. Kaplan-Meier-analyses were conducted stratified by pathological stage for DFS (Disease-Free-Survival) and OS (overall Survival). Results: 1,291 patients received NSS/Nx. 1,271 (98.5%) were R0/1. Median follow-up: 37.8 mo. (IQR 13.08; 65,74). 754 patients had ccRCC with a mean age of 63.5 y (SD: 12.1), 40% were female. 221 had pRCC, mean age was 62.1 (SD 12.6) and 36.8% were female. 165 had NOS, mean age was 63.3 (SD 12.4) and 36.8% were female. 151 patients had other histologies. Survival outcomes are reported in table 1. Conclusions: Morphologic RCC types and T-stages inform on recurrence and prognosis. Our study advises on real-world recurrence and survival rates in patients with different RCC types, which may be used to counsel patients with regards to adjuvant therapy in the clinic. A major limitation is the retrospective nature of the analysis. [Table: see text]