tbuckley/cabot-search huggingface dataset:
Impact of pre-treatment MRI capsular involvement and extraprostatic extension on metastasis free and overall survival in localized prostate cancer.
Authors: Abhishek Kumar, Dominic LaBella, Michael Snider, Scarlett Acklin-Wehnert, Rajan T. Gupta, Joseph Kamel Salama, Matthew J Boyer
Journal: Journal of Clinical Oncology (2024)

5097 Background: Multiparametric magnetic resonance imaging (mpMRI) is not currently included in prostate cancer (PC) staging. The purpose of this study was to test the association between mpMRI detected prostate capsule involvement and extraprostatic extension (EPE) with metastasis free survival (MFS) and overall survival (OS) in patients treated for localized PC. Methods: Patients treated for localized PC between 2000-2021 from the Veterans Affairs Prostate Data Core having an mpMRI prior to definitive treatment were identified. MRI reports were assessed for minor or significant capsule abutment (defined as greater than or equal to 1.5 cm of capsule contact or radiologist’s mention of long segment abutment), extracapsular extension (ECE), seminal vesicle invasion (SVI), or adjacent organ invasion (OI). mpMRI findings' impact on MFS by multivariable Fine-Gray competing-risks regression and OS by Cox regression were assessed. Results: Overall, 2,933 patients were included. Most pre-treatment mpMRIs (85%) occurred after 2016. 1,238 (42%) patients were Black. 569 (19%) patients had palpable disease. Median follow-up was 5 years. The 5-year cumulative incidence of metastasis was 10% (95% confidence interval (CI) 9-11%) and death was 7% (95% CI 6-9%). There were 643 (22%) patients with minor capsule abutment, 212 (7%) with significant capsule abutment, 281 (10%) with ECE, 103 (4%) with SVI, and 25 (1%) with OI. After controlling for age, race, prostate specific antigen level, grade group, clinical tumor stage, and treatment, the presence of significant capsule abutment, ECE, SVI, and OI were independently associated with MFS, but minor capsule abutment was not. On multivariable analysis controlling for the same factors, EPE (ECE, SVI, or OI) was associated with worse OS. Conclusions: In a modern, real-world cohort of localized PC patients from the largest integrated health system in the United States, significant capsule abutment and EPE on mpMRI are independently prognostic of MFS, but minor capsular abutment is not. EPE is associated with inferior OS. Given its independent prognostic value for MFS and association with OS, mpMRI should be more widely available to PC patients. Studies are ongoing to define its role as a standard staging tool. [Table: see text]
Long term cardiovascular adverse outcomes in testicular cancer survivors: Real-world U.S. population-based study.
Authors: Khalid Y. Alkhatib, John Pluta, Daniel Lee, Katherine L. Nathanson, Linda A. Jacobs, Thomas J. Guzzo, Nabil Adra, Jourik A. Gietema, David J. Vaughn, Phillip M. Pierorazio
Journal: Journal of Clinical Oncology (2024)

5042 Background: The focus of Testicular Cancer (TC) has shifted towards survivorship due to the high cure rates. With the increase in TC survivors population, long-term cardiovascular disease (CVD) have been suggested to be strongly linked with earlier treatment for TC by various hospital based small studies. As it is crucial to investigate this relationship at a population level to develop early prevention strategies to improve TC survivors' overall quality of life (QoL), we analyzed the U.S. The Behavioral Risk Factor Surveillance System (BRFSS) to describe the long-term outcomes of TC survivors in a real-world random population sample. Methods: Using BRFSS cycles between 2014 and 2022, we pulled all patients who reported having a history of TC and compared them to the rest of the men's population sample who had no history of cancer diagnosis. Using national complex weights, we estimated each group outcomes proportions. Further, we evaluated several complex-weighted logistic regression models adjusted for different covariates to describe the association of high blood pressure, high cholesterol, diabetes, BMI of &gt;25, angina, myocardial infarction (MI), and coronary heart disease (CHD). Results: Out of 3,077,806 participants, we identified 308 with a history of TC and 1,169,061 men with no history of cancer. After calculating descriptive demographics, our modeling analysis showed a consistent significant association in reporting history of Angina (OR range from 3.84 to 4.27), CHD or MI (OR range from 2.92 to 3.14). see table. Conclusions: Real-world data indicate alarming results of high prevalence CVD in TC survivors; our results confirm previously reported results from hospital-based cohorts. Our findings support immediate actions to develop and implement preventative strategies in TC survivors. [Table: see text]
Whole exome correlates in metastatic hormone sensitive prostate cancer (mHSPC): Results from E3805 CHAARTED.
Authors: Anis Hamid, Matias Vergara, Jihye Park, Tyler M Chinsky, Saud Aldubayan, Emily Grist, Gerhardt Attard, Eliezer Mendel Van Allen, Christopher Sweeney
Journal: Journal of Clinical Oncology (2024)

5088 Background: The landscape and clinical impact of genomic variants in mHSPC are incompletely understood. We have shown that deleterious germline BRCA2 alterations (alts) associate with shorter time to castration resistant prostate cancer (TTCRPC) on androgen deprivation therapy (ADT), but not on ADT plus docetaxel (ADT+D) (ASCO 2023). Somatic variation from tissue of patients (pts) with mHSPC is not well characterized and may influence therapeutic outcomes. Methods: We performed whole exome sequencing of HSPC specimens obtained at initial diagnosis and germline DNA from whole blood from pts in the CHAARTED trial (NCT00309985) of ADT vs ADT+D. Somatic single nucleotide variants (SNV) and allele-specific copy number alts (CNAs) were identified, including estimation of tumor mutational burden (TMB) and copy number burden (CNB). Prognostic effects were evaluated in both arms. Loss of selected tumor suppressor genes was defined by monoallelic or biallelic loss. TTCRPC and overall survival (OS) were estimated by Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox models. Results: After quality control, 68 tumor-normal cases were analyzed. The majority of pts had synchronous (51.5%) and high volume (58.8%) disease. Most frequent somatic SNVs were TP53 (33.8%), PTEN (7.4%), PIK3CA (5.9%) and SPOP (5.9%). AR amplification was uncommon (4.4%), however frequent MYC gain (60.3%) was seen as well as monoallelic deletion of NKX3-1, TP53, PTEN and BRCA2. Whole genome doubling occurred in 14.7%. Median TMB and CNB were 4.7 mut/Mb and 9.1%, respectively. CNB was elevated in synchronous (p=0.01) and high volume (p=0.046) disease. CNB greater than median was associated with shorter TTCRPC in the overall cohort (HR 2.06, 95%CI 1.13-3.75, p=0.015) and ADT+D arm (HR 2.98, 95%CI 1.17-7.58, p=0.016). The effect in the overall cohort was reduced after adjustment for volume and presentation (HR 1.72, p=0.091). A compounding effect of PTEN and TP53 alts was seen in the ADT arm where median TTCRPC for wild-type (WT), 1-gene hit, 2-gene hit was 19.6 mos, 8.5 mos, 6.3 mos, respectively. The median OS of WT vs 1-hit/2-hit loss was 47.1 mos vs 26.8 mos (HR 2.05, 95% CI 0.90-4.68, p=0.087). Similar differences in TTCRP and OS by PTEN/ TP53 status were not observed with ADT+D. Conclusions: The genomic landscape of mHSPC is characterized by frequent alts in putative drivers known to be enriched in mCRPC (Table). We observed a low rate of genomic instability and AR amplification/mutation similar to non-metastatic HSPC. Concordant with the STAMPEDE trial, greater CNB confers a higher risk of progression. Combined tumor suppressor gene alts associate with prognosis in mHSPC, which may differ by therapy intensification. [Table: see text]
Analysis of the efficacy and tolerance or darolutamide in combination with chemotherapy and ADT in patients with metastatic castration-sensitive prostate cancer (mCSPC) in the Spanish population in a daily clinic.
Authors: Javier Cassinello Espinosa, Lourdes Garcia Sanchez, Isabel Gallegos Sancho, Ricardo Sanchez-Escribano Morcuende, Carmen Perezagua Marin, Alicia Sanchez Cendra, Aldo Bruno Fiorini Talavera
Journal: Journal of Clinical Oncology (2024)

e17069 Background: Darolutamide is an inhibitor of the androgen receptor signaling pathway that increases overall survival both in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and in patients with high-volume mCSPC [Smith et al. N Eng J Med 2022]. Our objective is to analyze the efficacy and tolerance of darolutamide, in combination with chemotherapy and ADT (triplet therapy), in real-life data in several Spanish hospitals. Methods: A multicentric, observational, prospective study was performed in patients with mCSPC which started treatment with triplet therapy including darolutamide between 2022 and 2023 in some Spanish hospitals. A statistical analysis has been carried out with the SPSS v19 platform. Results: Between 2022 and 2023, 11 patients have been included, of which 10 have been analyzed. The mean age was 64 years (57-75 years), most patients with ECOG = 0 (60%) and ECOG = 1 (10%); the mean PSA diagnosis was 1025 ng/ml (12-4735 ng/ml). The majority of patients had a Gleason 9 (70%), 60% with extra regional lymph node metastases (M1a), 70% with bone metastases (M1b) and 60% with visceral metastases (M1c). The median time from diagnosis to statistical analysis was 580 days (366-700 days). The first patient was included in January 2022 and the last one was included in April 2023. Most patients started docetaxel and darolutamide was added a few weeks later. All patients achieved progression-free survival (PFS) with median of 14,5 months. The overall survival (OS) has not been reached. The median response time to 50% PSA was 3 months (2-8 months) and the median response time to 90% was 6 months (2-9 months); 30% of patients achieved complete PSA response. In relation to the objective response evaluation, 70% of the patients achieved a partial response, 30% stable disease and 11% presented disease progression; no complete radiological responses have been observed. Only 2 patients became castration resistant (one in 1 month and another in 11 months). Regarding adverse effects, 5 patients (50%) presented asthenia, 4 patients (40%) hematological toxicity (20% grade 3 neutropenia), 3 patients (30%) hot flashes, 2 patients (20%) elevated transaminases and 1 patient (10%) hyperglycemia; no patient had high blood pressure, weight gain, urinary tract infection or falls. Conclusions: The results of this analysis of real-life data confirm the efficacy of darolutamide within the triplet combination with chemotherapy and ADT in mCSPC patients, similar to the results of the already published phase III trial. Treatment with darolutamide was well tolerated. This analysis is limited by the retrospective nature and the small number of patients included.
Radical prostatectomy versus XRT for early-stage prostate cancer: A retrospective, propensity-matched cohort study of 29,970 patients.
Authors: Varada Salimath, James David Mackey, Brittany Miles, Ankit Mehta
Journal: Journal of Clinical Oncology (2024)

e17099 Background: Both radical prostatectomy and external beam radiation therapy (XRT) are standard therapeutic options for definitive treatment of early-stage prostate cancer. While both modalities are generally viewed as comparable when matched for risk stratification, there is a paucity of literature directly comparing their outcomes. Slow-growing malignancies are generally regarded as less radiation-sensitive, but this has not been conclusively proven in prostate cancer. Aggressive variants of prostate cancer have, however, been shown to have higher rates of radiation-resistance. Here, we present a retrospective database analysis comparing rates of bone metastases and mortality among early-stage prostate cancer patients treated with radical prostatectomy versus XRT. Methods: The TriNetX research network was used for this study, with patient cohorts created by the use of International Classification of Disease 10 (ICD-10) codes and Current Procedural Terminology (CPT) codes. Both cohorts consisted of men over age 50 with a diagnosis of prostate cancer (C61) and PSA levels below 10 ng/mL. One cohort was treated with surgical prostatectomy (1014183 or 55866), while the other underwent Intensity Modulated Radiation Treatment (77385 or 77386). The cohorts were balanced for age, race, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm, resulting in 14,985 patients in each arm. The cohorts were then evaluated for the development of bone metastases (C79.51) and mortality at five years. Results: Patients treated with prostatectomy were less likely to develop bone metastases within five years (3.4% vs 7.6%, RR 0.45, 95% CI (0.41,0.50), P value &lt;0.0001). Prostatectomy was also associated with lower five-year mortality (4.2% vs 7.9%, RR 0.53, 95% CI (0.48,0.58), P value &lt;0.0001). Conclusions: These results indicate that in early-stage prostate cancer, radical prostatectomy is associated with decreased rates of mortality and bone metastases within a 5-year period compared to XRT. Additional studies are needed to determine which prostate cancer variants are at increased risk of radiation treatment failure. Shared decision making regarding both outcomes and side effects is crucial when choosing a modality of definitive treatment in early-stage prostate cancer.
Intensification of ADT with enzalutamide in high-risk patients with biochemical relapse following radical prostatectomy undergoing salvage radiation: Initial results from RTOG 3506 (STEEL).
Authors: Edwin Melencio Posadas, Hiram Alberto Gay, Joseph P Rodgers, Todd Matthew Morgan, Ying Xiao, James Yu, Jeff M. Michalski, Myriam Bouchard, Neil B Desai, Ryan Funk, Thomas Pence Boike, Donald James Jurgens, Anthony C. Wong, Xinglei Shen, Lloyd T Miyawaki, Christopher S Bland, John Hairston, Howard M. Sandler, Stephanie L Pugh, Felix Y Feng
Journal: Journal of Clinical Oncology (2024)

5101 Background: Patients with high-risk features who experience biochemical relapse (BCR) after radical prostatectomy (RP) benefit from the addition of androgen deprivation therapy (ADT) to salvage radiotherapy (SRT). We hypothesized that intensification of androgen receptor (AR) blockade with enzalutamide would improve SRT outcomes for high-risk patients. Methods: Post prostatectomy prostate cancer patients who have had BCR (PSA ≥ 0.2 ng/mL) with at least 1 high-risk feature (Gleason 8-10, seminal vesicle invasion, pN1, persistent PSA &gt;0.1 ng/mL after RP, and PSA ≥ 0.7 ng/mL) were eligible. Patients were randomized 1:1 to 24 months of ADT with an LHRH analog (LHRHa) or intensified ADT comprised of LHRHa + enzalutamide. The primary endpoint was progression free survival (PFS) with progression defined as PSA ≥ 0.05 ng/mL or initiation of new therapy following SRT. The target accrual of 170 patients provided 80% power to detect a HR=0.65 using a one-sided logrank test with a type I error of 0.10. Results: Between April 2019 and August 2022, 188 patients were enrolled. The patient characteristics were well balanced between the two arms. Median age was 64 years. Nodal involvement (pN1), pT3a-b, and Gleason 9 were noted in 22%, 77%, and 52% of patients, respectively. Over 70% had &gt; 1 aggressive feature. Median follow-up time at the time of this report was 15.8 months. Prostatic fossa and pelvic SRT were mandatory. Para-aortic radiotherapy (RT), and lymph node and prostatic fossa lesion RT boosts were left at the discretion of the radiation oncologist. PFS favored the enzalutamide-intensified arm (HR=0.72, 80% confidence interval [CI]:0.56-0.94, one-sided p=0.14). Grade 3 adverse events (AEs) related to treatment in the standard versus enzalutamide arms were 11 vs. 23%, while Grade 4 AEs were 4% vs. 1%, respectively. The most common AEs (all grades, &gt;15%) included hot flashes, fatigue, diarrhea, and decreased lymphocytes. The grade 3+ AEs (&gt;3%) included decreased lymphocytes and hypertension. The largest differences (&gt;7%) in AEs included insomnia, decreased lymphocytes. Diarrhea was less frequent with enzalutamide (40% vs 54%). Conclusions: The addition of enzalutamide to standard ADT did not meaningfully increase toxicity. While there was a trend toward PFS benefit from intensification, it has not yet met statistical significance. Updates on PFS and other clinical endpoints including quality of life will be reported with longer follow-up. Clinical trial information: NCT03809000 .
PROact: A prospective phase II study to evaluate olaparib plus abiraterone and prednisone combination therapy in patients with metastatic hormone sensitive prostate cancer with HRR gene mutation.
Authors: Junlong Zhuang, Shun Zhang, Xuyu Zhang, Xuefeng Qiu, Hongqian Guo
Journal: Journal of Clinical Oncology (2024)

5082 Background: Approximately 10% - 15% of patients with metastatic hormone sensitive prostate cancer (mHSPC) harbor loss-of-function mutations in homologous recombination repair (HRR) genes. Although olaparib plus abiraterone and prednisone has significantly prolonged overall survival in metastatic castration resistant prostate cancer patients, there is a lack of evidence regarding the efficacy and safety of this combination therapy in patient with mHSPC. Here, we report the interim analysis results of PROact study, the first phase Ⅱ trial to evaluate the effects of olaparib plus abiraterone and prednisone in mHSPC patients with HRR gene mutation. Methods: This was a single center, single arm, phase Ⅱ trial ( NCT05167175 ) conducted in male patients with mHSPC who had at least one HRR gene mutation ( BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD 51C, RAD51Dand RAD54L) as determined by tissue-NGS. Patients were administered olaparib 300 mg BID plus abiraterone 1000 mg QD and prednisone 5 mg QD. Previous treatment with new hormonal agent (NHA) was not allowed. The primary endpoint was 1-year radiographic progression-free survival (rPFS) rate per PCWG3-modified RECIST 1.1 by investigator assessment. The secondary endpoint included prostate-specific antigen (PSA) response rate, objective response rate (ORR), and adverse events. Results: Between May 19, 2022 and Dec 8, 2023, a total of 30 patients were enrolled and administered combination therapy. All the patients had de novo mHSPC, and the median age was 68 (range 49-85), with a median PSA of 166 ng/mL at baseline. A total of 7 HRR mutations were identified, included BRCA2 (n=11), CDK12 (n=8), ATM(n=6), PALB2 (n=2), CHEK2 (n=2), RAD51B (n=2) and RAD51D (n=1). As of Jan 29, 2024, the median follow-up was 7.1 months. In the 30 patients who had PSA response evaluated, PSA50 response rate achieved 100% (30/30), and the PSA90 response rate was 96.7%(29/30). In the 12 patients who had RECIST assessment, the objective response rate was 91.7% (11/12). Two achieved complete response, nine obtained partial response, and one had stable disease. The treatment was well tolerated, with 7(23.3%) patients experienced ≥grade 3 treatment-related adverse events (TRAEs). Common TRAE was anemia. Conclusions: This was the first trial to show efficacy and an acceptable safety profile of olaparib plus abiraterone and prednisone in mHSPC patients with HRR mutation. Data of primary endpoint of 1-year rPFS will be reported in the due time. Clinical trial information: NCT05167175 .
ProstACT GLOBAL: A phase 3 study of best standard of care with and without 177Lu-DOTA-rosopatamab (TLX591) for patients with PSMA expressing metastatic castration-resistant prostate cancer progressing despite prior treatment with a novel androgen axis drug.
Authors: Oliver Sartor, Scott T. Tagawa, Nat Lenzo, David Cade, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2024)

TPS5115 Background: The treatment of advanced prostate cancer (PC) is challenging, with no curative therapy to date and undesirable side effects that may impact patient quality of life. Monoclonal antibodies enable high specificity with low rates of off-target organ exposure, prolonged retention in PSMA+ tumors, and a predictable safety profile. There is a strong rationale for further investigation of the 177 Lu-labeled, chelator-conjugated antibody, 177 Lu-DOTA-rosopatamab (hereafter, TLX591), with prior studies demonstrating a favorable safety profile and efficacy, particularly with a fractionated (dose-dense) regimen Phase 1 ProstACT SELECT preliminary results demonstrate consistent uptake between TLX591 and 68 Ga-PSMA-11 imaging and reinforces advantages of this first-in-class radio-antibody drug conjugate investigational therapy. Methods: In this multinational, multicenter, prospective, randomized, open label phase 3 study, patients (N=400) with PSMA-expressing metastatic castration-resistant PC (mCRPC) that have progressed despite prior treatment with an androgen-receptor pathway inhibitor (ARPI) will be enrolled in a 2:1 ratio to receive best protocol-defined standard of care (SoC) with or without 2 intravenous injections of 2.8 GBq of TLX591, given 14 days apart. SoC may be alternative ARPI or docetaxel. Eligible patients must have received 1 prior ARPI in the mCSPC, nmCRPC, or 1L mCRPC setting. Patients must have 150x10 9 /L platelets, and have PSMA-positive disease on 68 Ga-PSMA-11 PET/CT imaging. The primary endpoint is radiographic progression-free survival. Secondary endpoints include 5-year overall survival, tumor objective response rate, time to symptomatic skeletal event, health-related quality of life, and treatment-related adverse events count. An alpha control and 95% confidence intervals will be used; patients will be substratified between TLX591 + 2 nd ARPI or TLX591 + docetaxel. This study is currently enrolling. This study is funded by Telix Pharmaceuticals. Clinical trial information: NCT04876651 .