tbuckley/cabot-search huggingface dataset:
Time to next systemic therapy after stereotactic body radiation therapy for oligoprogressive metastatic castrate-resistant prostate cancer.
Authors: Corbin J. Eule, Nellowe Candelario, Tyler P. Robin
Journal: Journal of Clinical Oncology (2024)

62 Background: Patients with castrate-resistant prostate cancer (CRPC) with progressive disease are generally require a change/escalation in systemic therapy. For patients with limited ( ≤3) sites of progressive disease (oligoprogression), metastasis-directed therapy with stereotactic body radiation therapy (SBRT) may allow a longer interval before next line systemic therapy, but there is limited data describing this approach. Methods: This is a retrospective study of patients with oligoprogressive metastatic CRPC (omCRPC) treated with SBRT at a single center between 2011-2022. The primary endpoint was time to next systemic therapy (TTNST) after SBRT. Secondary endpoints included overall survival (OS) after SBRT and TTNST stratified by presence of untreated non-progressing metastases. Results: Thirty-two patients with omCRPC received SBRT to 38 metastases. Patients had a median age of 72.5 years (range 50.6-84.3) and median PSA 6.85 ng/mL (range 0.39-922.0) at time of SBRT. The majority had an ECOG of 1-2 (29 patients, 90.6%) and metastases detected on conventional CT and/or bone scans (26 patients, 81.3%). The most commonly utilized SBRT regimen was 3000 cGy in 5 fractions (18 metastases, 47.4%) (Table). Sixteen patients were treated to all known sites of disease, whereas 16 patients received SBRT to oligoprogressive metastases but had at least one untreated non-progressing metastasis at the time of SBRT. Of 32 patients, 23 (65.7%) received SBRT to bone only, 3 (9.4%) to lymph node (LN) only, and 6 (18.8%) to other sites (pelvic tumor, n=2; pelvic tumor + LN, n =1; LN + bone, n=1; dura + bone, n=1; liver, n=1). Patients had received a median of 1.0 prior line of androgen receptor signaling inhibitors and were predominantly (26 patients, 81.3%) chemotherapy naïve. Following SBRT, the median TTNST was 10.1 months and median OS was 41.3 months. For patients with 0 versus ≥1 untreated non-progressing metastasis, TTNST was 11.3 versus 8.7 months, respectively (HR 0.67, 95% CI 0.33-1.36, logrank p=0.24). There were no grade ≥3 toxicities due to SBRT. Conclusions: In this cohort, patients with omCRPC treated with SBRT delayed the next line of systemic therapy for a median of 10.1 months. SBRT in patients with omCRPC may delay initiation of next line systemic therapy in well selected patients, including those with ≥1 untreated non-progressing metastases. [Table: see text]
PSMA PET imaging for evaluation of recurrent or persistent prostate cancer after primary prostate radiation.
Authors: Richard Bennett, Eric Li, Austin Y. Ho, Jonathan Aguiar, Ashorne Krithiesh Mahenthiran, Sai Kumar, Chalairat Suk-ouichai, Clayton Neill, Hiten Dilip Patel, Edward M. Schaeffer, Hatice Savas, Ashley Ross
Journal: Journal of Clinical Oncology (2024)

35 Background: PSMA PET is increasingly utilized for the evaluation of disease stage at biochemical recurrence. Here we evaluate the association of clinico-pathologic features with PSMA findings in biochemically recurrent patients after primary prostate radiation therapy (RT). Methods: We queried the Northwestern Medical System Electronic Data Warehouse between July 2021 and March 2023 to identify 122 men treated with primary RT for presumptive localized prostate cancer who subsequently underwent Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT for staging. Patient characteristics, including demographic, clinical, pathological, and imaging variables were obtained. PSMA positivity for suspicious nodal or metastatic disease was determined based on radiology interpretation, with equivocal or likely benign lesions considered as negative findings. Patients with incomplete clinical history (n=3) were excluded. Clinical variables were compared using a Wilcoxon rank-sum and Fisher’s exact tests. Regression analysis was performed to determine variables associated with PSMA positivity in biochemically recurrent patients. Statistical significance was determined if the p-value was less than 0.05. Results: Among the 119 men staged with PET PSMA after RT, median PSA was 3.18 (IQR 1.35, 5.55 ng/mL). 78% (93/119) were found to have suspicious PSMA positive disease. 39% had PSMA positivity in the prostate only (46/119), 6.7% had pelvic nodal disease (8/119), and 33% had extrapelvic disease (39/119). On univariable regression analysis, PSA at the time of PSMA was the only factor associated with PSMA positivity (OR 1.32 per 1 point increase, 95% CI 1.10, 1.67, p=0.01; Table). Higher PSAs at the time of scan were additionally associated with distant recurrence (73.3% of men with distant recurrence if scanned at PSA &gt;10ng/mL versus 31.9% if scanned at PSA &lt;4ng/mL p=0.029). 20% (9/46) of men with PSMA positivity within the prostate were biopsied identifying 78% (7/9) positivity, of which 67% (4/6) receiving treatment selected management with salvage treatments. Conclusions: Patients with prostate cancer initially treated with RT showed significant rates of PSMA positive disease even when scanned at low PSAs (including many below the nadir+2ng/mL definition). Evaluation at low PSAs favors the identification of localized disease only which can be cured by salvage therapy if confirmed by biopsy (i.e. prostatectomy, cryoablation, HIFU). [Table: see text]
Overall survival with darolutamide vs placebo in combination with androgen-deprivation therapy (ADT) and docetaxel: A sensitivity analysis from ARASENS accounting for subsequent therapy.
Authors: Neal D. Shore, Bertrand F. Tombal, Maha H. A. Hussain, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Todd Fralich, Rui Li, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2024)

166 Background: Darolutamide (DARO) + ADT + docetaxel (DOC) is approved for metastatic hormone-sensitive prostate cancer (mHSPC) based on the phase 3 ARASENS study (NCT02799602). To address the impact of informative intercurrent events (eg, use of subsequent therapy) in censored patients (pts), as defined by the European Medicines Agency, we performed a post hoc sensitivity analysis of OS. Methods: Pts with mHSPC were randomized 1:1 to oral DARO 600 mg twice daily or placebo (PBO) + ADT + DOC. The primary endpoint was OS using a log-rank test, with HR (95% CI) calculated by Cox model, stratified by extent of disease (EoD; nonregional lymph node vs bone ± lymph node vs visceral ± lymph node/bone metastases) and alkaline phosphatase (&lt; vs ≥ upper limit of normal). Pts with no documented death were censored at last known alive or data cut-off date, whichever was earlier. The post hoc sensitivity analysis counted initiation of subsequent systemic antineoplastic therapy as an event in censored pts still alive at end of follow-up. In addition planned sensitivity analyses used an unstratified log-rank test/Cox model, a log-rank test/Cox model with stratification factors from electronic case report forms, and a log-rank test/Cox model with EoD stratification factors from central imaging review. Results: In the primary analysis DARO + ADT + DOC significantly improved OS ( P&lt;0.0001; Table), despite a high percentage of pts who entered follow-up in the PBO group receiving subsequent life-prolonging systemic therapies (374/495, 76%). Time to first subsequent systemic antineoplastic therapy (a key secondary endpoint) was significantly longer with DARO + ADT + DOC vs PBO + ADT + DOC (HR 0.39, 95% CI 0.33–0.46, P&lt;0.001). Findings from the post hoc sensitivity analysis counting initiation of subsequent systemic antineoplastic therapy as an event in censored pts (pts with events: DARO 300/651, 46.1%; PBO 476/654, 72.8%) and the planned sensitivity analyses were consistent and supported the primary OS analysis (Table). Treatment-emergent adverse events (TEAEs) were similar between groups. TEAEs led to DARO/PBO discontinuation in 13.5%/10.6% of pts. Conclusions: The results of the post hoc and planned sensitivity analyses were consistent with and supportive of the ARASENS primary OS analysis. These data reinforce DARO + ADT + DOC as an effective and well tolerated new standard of care for early treatment intensification in pts with mHSPC. Clinical trial information: NCT02799602 . [Table: see text]
Remote delivery of cancer genetic testing in veterans with metastatic prostate cancer: A Million Veteran Program study.
Authors: Robert Bruce Montgomery, Julie Ann Lynch, Jessica Brown, Kara Noelle Maxwell, Nismeta Kabilovic, Katie Stoll, Julie Simon, Maria Kogan, Stacey Whitbourne, J. Michael Gaziano, Heather H. Cheng, Ruth Douglas Etzioni, Colin C. Pritchard
Journal: Journal of Clinical Oncology (2024)

60 Background: Germline pathogenic alterations are found in approximately 10% of men with metastatic prostate cancer (mPC) and can inform precision therapy, surveillance, and cancer prevention for family. National guidelines recommend germline genetic testing be offered to all men with mPC, yet uptake of testing in the community has been documented to be 6-12% with many barriers to testing. We conducted a study to determine uptake of testing using remote consenting and testing for veterans with mPC who had participated in the Veteran’s Administration Million Veteran Program (MVP). We wanted to know if remote testing could overcome limited point-of-care counseling and ordering to increase uptake of germline testing. Methods: This prospective study enrolled veterans who participated in MVP study with a diagnosis of mPC. Veterans were contacted by mail with an option to opt-out of further contact. Those who did not opt-out were mailed information regarding the study and received a follow-up phone call to establish interest in germline testing with a CLIA-level germline test (BROCA). Those expressing interest provided verbal informed consent and were mailed a saliva collection kit for a multigene cancer predisposition gene panel test (University of Washington). Results were disclosed by phone and mailed to the patient with genetic counseling support and was also sent to the oncology provider by email, phone or both. Two research coordinators and two part-time genetic counselors provided review of consenting, counseling and return of results. Results: As of September 17, 2023, 1952 veterans who were alive with an incident diagnosis of mPC were identified through MVP and did not opt out of further contact. Informational letters were sent to the home address of all eligible participants. 681 (22%) of veterans were reached and completed informed consent. All participants were then sent a saliva kit and 432 (63%) completed testing, with 23 tests currently pending. Among the participants, 70% were White, 21% were Black, 0.5% Asian and 8% unknown. Thirteen percent (53/409) were found to have a germline pathogenic variant. Conclusions: We evaluated uptake of germline testing using a remote, VA system-wide approach to identify and offer genetic testing for veterans with mPC with access and cost issues removed. We completed germline testing at rates significantly higher than those reported in the community with modest personnel requirements, while also reaching a more diverse population of patients. Remote genetic testing can improve uptake of testing in large integrated health care systems.
Temporal and regional patterns of prostate cancer positron emission tomography imaging among commercial insurance beneficiaries in the United States.
Authors: Michael Leapman, Jessica B. Long, Sarah J. Westvold, Maximilian Rabil, Preston Sprenkle, Isaac Yi Kim, Lawrence Saperstein, Jaleh Fallah, Daniel L. Suzman, Catherine Lerro, Jianjin Xu, Paul Gustav Kluetz, R. Jeffrey Karnes, Natalia Kunst, Shi-Yi Wang, Xiaomei Ma, Cary Philip Gross
Journal: Journal of Clinical Oncology (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&lt;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&lt;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&lt;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&lt;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.
Low- and high-volume disease in mHSPC, from CHAARTED to PSMA-PET: An international multicenter retrospective study.
Authors: Lena Unterrainer, Thomas A. Hope, Wolfgang P. Fendler, Honest Ndlovu, Francesco Barbato, Mike Sathekge, Ken Herrmann, Johannes Czernin, Jeremie Calais
Journal: Journal of Clinical Oncology (2024)

44 Background: High-volume disease (HVD) and low-volume disease (LVD) definitions are based on conventional imaging (CI = CT + bone scan (BS)) according to CHAARTED. Volume of disease is associated with overall survival and used for treatment decisions in mHSPC patients. It remains unknown how these definitions transfer to PSMA-PET. Methods: mHSPC patients from 4 international sites who underwent PSMA-PET+BS within a maximum time interval of 100 days and without any new treatment in between were retrospectively included. CHAARTED stratification into HVD/LVD was applied to BS, CT, MRI and PSMA-PET. HVD was defined by the presence of visceral metastases and/or ≥ 4 bone metastases (with ≥ 1 beyond spine / pelvis). EXINIbone 3.4 (EXINI Diagnostics) was used for the automated bone scan index (aBSI) and the number/localization of lesions on BS. The whole-body (WB) PSMA-PET positive tumor volume (PSMA-TV) was obtained using a semi-automatic thresholding method on Affinity 3.0.2 (Hermes Medical Solutions). Results: Fifty-sevenpairs of PSMA-PET/CT+BS were included (median PSA 226.0 (0.2–2840.0 ng/ml). Based on CI, 16/57 patients had CI-HVD (28.1%) and 41/57 CI-LVD (71.9%). Based on PSMA-PET, 25/57 patients had PSMA-HVD (43.9%) and 19/57 PSMA-LVD (33.3%), 13/57 (22.8%) patients had on PSMA-PET no PSMA-positive or only local / N1-disease. Upshift and downshift from CI to PSMA-PET occurred in 22/57 (38.6%): 9/57 (22.0%) patients were upstaged and 13/57 (22.8%) were downstaged by PSMA-PET. The downshifted patients had no PSMA-PET-positive lesion or only in the prostate fossa while CI was M1 disease. The mean WB-PSMA-TV and aBSI were for CI-HVD was 778.2 ml (0.3–3734.0) and 3.8% (0–11.7), for CI-LVD 51.6 ml (0–228.0) and 0.1% (0–0.6), for PSMA-HVD 573.7 ml (7.9–3734.0) and 2.6% (0–11.7) and for PSMA-LVD, 49.4 ml (1.6–228.0) and 0.1% (0–0.6), respectively. Conclusions: Stage migration between LVD and HVD from CI to PSMA-PET occurs both by up- and downstaging. HVD/LVD based on PSMA PET/CT should be redefined based on patients’ outcome.
Performance of the F-PSMA 1007 PET/CT for high-risk prostate cancer staging: Experience from a Latin American reference center.
Authors: Sebastian Peña Rodriguez, Cesar Alejandro Diaz Ritter, Juan Ignacio Caicedo, Natalia Ramirez, Julian Rojas, Andres Felipe Gutierrez, Maria Paula Mogollón, Camilo Medina
Journal: Journal of Clinical Oncology (2024)

286 Background: Diagnostic staging in high-risk prostate cancer patients seeks to define the local extent of the disease as well as determine the presence of lymph nodes and distant metastases. Molecular imaging, such as PET PSMA, provides higher sensitivity and specificity for the detection of nodal and distant metastases compared to conventional imaging. 18 F-PSMA-1007 is radiotracer that represents a cost-effective alternative to 68 Ga-PSMA-11, although evidence is limited. We aim to describe the performance of PSMA-1007 in the staging of patients with high risk for prostate cancer in a Latin America reference center. Methods: We performed a cross-sectional study that included prostate cancer patients who underwent 18 F-PSMA1007 PET/CT for initial staging in our center of reference between 2020-2023. Descriptive analysis was performed with frequencies for discrete variables, and central tendency and dispersion measures for continuous variables. High risk was defined using the NCCN prostate cancer guidelines. Contingency tables were designed to evaluate associations between groups. To compare categorical variables, we use Chi-square and ANOVA for continuous variables. This analysis was performed using Jamovi 2.3.21 statistical software. Results: Two hundred and seventeen patients were included. The median age was 67 years. The median PSA distribution was 12 ng/ml. The most frequent Gleason group was group 4 (42,7%), followed by group 3 (25,5%). The most prevalent results on the PET pattern are presented in Table. 32% of the patients presented positive lymph node findings. Before the F-PSMA 1007 PET/CT, 24% of the patients had lymph node involvement identified and 33.2% had negative lymph nodes with conventional imaging. These values changed to 39% and 56% respectively, with the F-PSMA 1007 PET/CT. Bone was the most frequent metastasis site (14,3%), followed by extrapelvic lymph node metastasis (12%). A favorable correlation between higher PSA levels and stratified risk assessment by PSMA pattern was evident (p&lt; 0.001). Conclusions: 18 F-PSMA-1007 is an innovative radiotracer that can be used to evaluate the extension of prostate cancer involvement. Future studies with prospective cohorts should be carried out to establish analyses between 18 F-PSMA-1007 use and its influence on the oncological management of these patients.[Table: see text]
Enfortumab vedotin (EV) in combination with pembrolizumab (P) versus chemotherapy in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC): Subgroup analyses results from EV-302, a phase 3 global study.
Authors: Michiel Simon Van Der Heijden, Thomas Powles, Shilpa Gupta, Jens Bedke, Eiji Kikuchi, Ronald De Wit, Matt D. Galsky, Ignacio Duran, Andrea Necchi, Margitta Retz, Evan Y. Yu, Jean H. Hoffman-Censits, Gopa Iyer, Se Hoon Park, Wen-Pin Su, Hema Parmar, Xuesong Guan, Seema Rao Gorla, Blanca Homet Moreno, Begoña Pérez Valderrama
Journal: Journal of Clinical Oncology (2024)

LBA530 Background: EV-302/KEYNOTE-A39 (NCT04223856) is a phase 3, open-label, randomized, global study comparing EV+P with platinum-based chemotherapy for first-line (1L) treatment of patients (pts) with la/mUC regardless of cisplatin eligibility or PD-L1 expression status. In EV-302, EV+P demonstrated a statistically significant and clinically meaningful benefit compared with platinum-based chemotherapy for the dual primary endpoints of progression-free survival (PFS) (hazard ratio [HR]: 0.45; P&lt;0.00001) and overall survival (OS) (HR: 0.47; P&lt;0.00001) in the overall pt population (Powles ESMO 2023). Here we present results not previously presented of prespecified subgroup analyses. Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg; Days 1 and 8; IV) and P (200 mg; Day 1; IV) or gemcitabine with cisplatin or carboplatin. Select secondary endpoints included confirmed objective response rate (cORR), duration of response, and safety. For PFS and OS, an HR between treatment arms was estimated using a stratified Cox proportional hazards regression model controlling for the stratification factors (cisplatin eligibility, PD-L1 status [high/low], liver metastases [yes/no]) for each predefined subgroup. Results: 886 pts (EV+P: 442, chemotherapy: 444) were randomized; baseline pt and disease characteristics were balanced between groups. PFS and OS were prolonged for EV+P among prespecified subgroups, including race, cisplatin eligibility, PD-L1 expression, metastatic site, liver involvement, and renal function. Select subgroup data not previously presented for OS are presented in the Table. Kaplan-Meier curves for PFS (liver metastases, cisplatin eligibility, and PD-L1 status) and OS (liver metastases) will also be presented. Conclusions: EV+P significantly improved outcomes in pts with previously untreated la/mUC compared with chemotherapy; OS benefit was consistently observed across select prespecified subgroups, including those historically associated with poor prognosis. The results of these subgroup analyses support the findings of the primary analysis, which indicate that EV+P is a potential new standard of care for 1L la/mUC. Clinical trial information: NCT04223856 . [Table: see text]