tbuckley/cabot-search huggingface dataset:
Final study analysis of PRINT: Prostate cancer intensive, non–cross-reactive therapy for CRPC.
Authors: Bobby Chi-Hung Liaw, Himanshu Joshi, Tianxiang Sheng, Che-Kai Tsao, Matt D. Galsky, Richard Lorne Bakst, Robert Stewart, Richard Stock, William K. Oh
Journal: Journal of Clinical Oncology (2024)

147 Background: The long-standing approach to mCRPC management has been to treat sequentially with one agent until resistance is met. PRINT explores the efficacy of treating mCRPC with a rapidly-cycling, non–cross-reactive regimen as a way to more effectively treat an intrinsic heterogeneous disease, delay or prevent drug resistance, and minimize treatment toxicity. Methods: All patients receive treatment with 3 consecutive treatment modules, each lasting 12 weeks: 1. abiraterone acetate 1000 mg PO daily + prednisone 5 mg PO BID; 2. cabazitaxel 20 mg/m2 IV + carboplatin AUC 4 IV q3 weeks; 3. enzalutamide 160 mg PO daily + radium-223 55 kBq/kg IV q4 weeks. Upon completion of regimen, patients are followed on ADT alone. Primary endpoint for the study is time to progression (TTP), either by PSA or imaging. Secondary endpoints are PSA response rate with each module, changes to alkaline phosphatase levels, and safety. Results: From 3/2017 to 11/2020, 40 men with mCRPC were enrolled, with 33 completing the 9-month study regimen and evaluable for endpoint analysis. With median follow up of 139 weeks, median TTP after regimen completion was 15.9 weeks (95% CI 10.6-25.0 weeks), which did not meet prespecified TTP of 20 weeks to be considered a significant improvement over standard management. PSA response rates showed successive improvement with each sequential treatment module (Table). 77.8% of patients with elevated baseline alkaline phosphatase levels had normalization post-treatment. Previously reported, the treatment regimen was well-tolerated, with few grade 3/4 AE’s attributable by the investigator to the study regimen. Five patients (15.2%) were able to remain on post-study surveillance with ADT alone without the addition of a mCRPC agent for over a year, with one patient subsequently discontinuing ADT with PSA remaining undetectable in setting of recovering testosterone levels. Conclusions: Treatment of mCRPC with a rapidly cycling non–cross-reactive regimen did not significantly improve time to disease progression as compared to standard management. However, it is associated with significant antitumor response, with potential for long-term suppression of disease. Additional analysis into clinicopathologic and genomic factors that may predict for prolonged disease control is ongoing. Clinical trial information: NCT02903160 . [Table: see text]
Phase II study of axitinib intensification compared to nivolumab alone after induction with ipilimumab plus nivolumab in patients with mRCC without previous complete response (AxIn study).
Authors: Chiara Ciccarese, Elena Verzoni, Davide Bimbatti, Sebastiano Buti, Fabio Calabrò, Luca Galli, Sarah Scagliarini, Giuseppe Fornarini, Cinzia Baldessari, Domenico Bilancia, Gaetano Facchini, Carlo Cattrini, Cristina Masini, Maria Olga Giganti, Giuseppa Scandurra, Franco Nole, Alfredo Berruti, Michele Milella, Lorenzo Antonuzzo, Roberto Iacovelli
Journal: Journal of Clinical Oncology (2024)

TPS494 Background: The combination of nivolumab plus ipilimumab (N+I) is able to increase the overall survival (OS), progression free survival (PFS) and overall response rate (ORR) compared to sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC) at intermediate or poor prognosis. However, the rate of pts with partial response to N+I (32%) is lower of that reported with the combination of axitinib plus pembrolizumab (51%). Moreover, analysis of outcome based on the depth of response strongly suggests a connection between response and survival. This study aims at investigating the efficacy of an intensified strategy with axitinib added to nivolumab in mRCC pts without complete response at the end of N+I induction. Methods: AxIn study (NCT05817903) is a randomized, open-label, multicenter, phase 2 trial evaluating in mRCC pts who completed induction with N+I without complete response or progressive disease, whether the intensification of therapy by adding axitinib to the standard nivolumab can increase the response rate and improve the survival compared to nivolumab alone. Eligible pts with partial response or stable disease after completion of N+I induction as first-line therapy, without any toxicity ≥ G2, and candidates to maintenance nivolumab as per standard clinical practice will be randomized 1:1 to intensification of therapy with axitinib in addition to nivolumab (Arm A) or nivolumab alone (Arm B). The primary endpoint is to assess the ORR of pts treated with the intensification of axitinib plus nivolumab compared to the standard of care of nivolumab monotherapy. Secondary endpoints include PFS, OS, depth of response, duration of response, quality of life, and safety. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05817903 .
Germline pathogenic variants in universal screening of genitourinary malignancies: A multisite single institution prospective study.
Authors: Mouneeb Choudry, Adri Durant, Victoria Edmonds, Christoper Warren, Katie Kunze, Michael A. Golafshar, Sarah M. Nielsen, Brandie Heald, Jack R. Andrews, N. Jewel Samadder, Mark Tyson
Journal: Journal of Clinical Oncology (2024)

376 Background: Germline genetic testing (GGT) is becoming increasingly important in the management of genitourinary (GU) malignancies as novel targeted drug therapies emerge. Selection for genetic studies and testing has historically been highly selective and based on pathologic characteristics, family history, and age of diagnosis. The aim of our study was to investigate the prevalence of pathogenic variants (PGVs) in inherited cancer susceptibility genes utilizing a universal testing approach and to characterize the rate of PGVs that would have been missed based on current NCCN guidelines. Methods: A multisite single-institutional prospective study (INTERCEPT) offered GGT to all patients with new or active diagnoses of GU malignancies (bladder, prostate, and renal cancers) from April 1, 2018 to March 31, 2020 at Mayo Clinic Arizona, Mayo Clinic Florida and Mayo Clinic Rochester. Participants were offered GGT with a panel of &gt;80 genes through Invitae Corp. Demographic, tumor characteristics and genetic results were evaluated. PGVs were classified as high-, intermediate-, or low- penetrance variants based on published literature. Respective NCCN GU GGT guidelines were used to determine if the PGVs discovered using our universal testing approach would have been missed with guideline-directed GGT. Results: A total of 3095 pan-cancer patients were enrolled in the study; 601 of which had a GU malignancy including: prostate cancer (358 patients), renal cancer (137), and bladder cancer (106). The mean age of enrollment was 66.8 years (SD 9.1), 89% were male, and 85.9% of patients were Non-Hispanic white. PGVs were identified in 82 of all GU patients (13.6%) and variants of undetermined significance (VUS) in 289 (48.1%) patients. PGV prevalence breakdown by cancer type was: 13.7% of prostate, 13.1% renal, and 14.2% bladder cancer patients. The proportion of high penetrance PGVs varied by malignancy type. Of all patients, 326 (54.2%) had advanced (stage III/IV) disease and 377 (64.4%) of these were metastatic upon initial evaluation. The majority of all PGVs identified were incremental, defined as PGVs that would not have been identified based on guideline-concordant GGT: 100% (15/15 patients) with bladder, 77.8% (14/18) with renal, and 57.1% (28/49) with prostate cancer. Conclusions: Universal GGT for prostate, renal and bladder cancer revealed that over 1 in 10 patients harbored potentially actionable PGVs, most of which would not have been identified with guidelines-based GGT. Utilization of GGT can impact our understanding of GU cancer pathogenesis, aid in familial cascade testing, and influence treatment decisions.
Venous tumor thrombus destinations in patients with renal cell carcinoma.
Authors: Reza Nabavizadeh, Rodrigo Pessoa, John Cheville, Christine M. Lohse, Brian Addis Costello, Fabrice Lucien, Houston R. Thompson, Stephen A. Boorjian, Bradley C. Leibovich, Vidit Sharma
Journal: Journal of Clinical Oncology (2024)

381 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&lt;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&lt;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&lt;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&lt;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.
Rezvilutamide in combination with androgen-deprivation therapy, with or without salvage radiotherapy, for patients experiencing biochemical recurrence following radical prostatectomy: A multi-center, open-label, two-cohort study.
Authors: Shun Zhang, Linfeng Xu, Xuefeng Qiu, Junlong Zhuang, Qing Zou, Junqi Wang, Hongqian Guo
Journal: Journal of Clinical Oncology (2024)

TPS355 Background: Rezvilutamide, a novel androgen-receptor inhibitor exhibiting minimal blood-brain barrier penetration, has demonstrated robust antitumor efficacy in metastatic castration-resistant prostate cancer and high-volume, metastatic, hormone-sensitive prostate cancer, which received approval from the Chinese National Medical Products Administration in 2022. The standard management for biochemical recurrence (BCR) post-prostatectomy typically involves androgen-deprivation therapy (ADT) alone or in combination with salvage radiotherapy (SRT). This study aims to evaluate the efficacy and safety of rezvilutamide plus ADT, with or without SRT for patients with BCR post-prostatectomy. Methods: In this multi-center, open-label, two-cohort study, patients with postoperative pathology-confirmed pN0 or pNx prostate adenocarcinoma who manifested BCR subsequent to radical prostatectomy (evidenced by two successive elevated serum prostate-specific antigen [PSA] measurements between 0.2-2 ng/ml, without identifiable local or metastatic recurrence on computed tomography and bone scans) would be enrolled. Cohort 1 participants will undergo 6 months of ADT, 6 cycles of rezvilutamide (240 mg/day, spanning 28 days per cycle), and SRT. Those in Cohort 2, either declining or ineligible for SRT, will receive 12 months of ADT combined with 12 cycles of rezvilutamide. The choice of ADT regimens rests with the investigators. The primary endpoints are the 2-year biochemical progression-free survival (bPFS) rate for Cohort 1 and the 3-year bPFS rate for Cohort 2. Secondary endpoints encompass bPFS, radiographic PFS, metastasis-free survival, and rates of undetectable PSA (with PSA levels &lt; 0.1 ng/ml). Additionally, safety profiles, overall quality of life, testosterone recovery rates post-treatment initiation, and the time to testosterone recovery post-treatment discontinuation will be appraised. The study acquired ethical approval on November 24th, 2022, and subsequently commenced recruitment. As of now, 22 out of the planned 96 patients have been enrolled. Clinical trial information: NCT05753566 .
Characteristics and outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177–PSMA-617 (PSMA-RLT) in a real-world setting.
Authors: David Kersting, Moon-Sung Kim, Lukas Puellen, Kathi Seidl-Rathkopf, Nicole Schinwald, Philani Mpofu, Ivy Altomare, Arun Sujenthiran, Trevor Joseph Royce, Christoph Buhl, Viktor Grünwald, Ken Herrmann, Jens Kleesiek, Boris A. Hadaschik
Journal: Journal of Clinical Oncology (2024)

143 Background: The VISION trial demonstrated a survival benefit of PSMA-RLT treatment (tx) for pts with PSMA-positive mCRPC. However, outcomes in a real-world setting are unknown. PSMA-RLT has been used at Essen University Hospital (UKE) in Germany since 2017. This retrospective cohort study describes characteristics and real-world overall survival (rwOS) of pts with mCRPC treated with PSMA-RLT. We contextualize these findings with results from a US-based mCRPC cohort that did not receive this novel tx. Methods: The UKE cohort included mCRPC pts treated with ≥ 1 cycle of PSMA-RLT from 11/2017 to 10/2022. Data comprised structured and unstructured data from UKE’s electronic health record (EHR). The US cohort was selected from the nationwide EHR-derived Flatiron Health database. It included pts with mCRPC diagnosis (dx) from 01/2014 to 09/2021 who received tx (=index tx) following ≥ 1 taxane and ≥ 1 androgen receptor pathway inhibitor (ARPI). Results: In the UKE cohort (N = 219, median (med) age: 73, interquartile range (IQR): 67, 78) med time from initial dx and mCRPC dx to the initiation of PSMA-RLT was 69 mos (IQR: 42, 128) and 23 mos (IQR: 13, 40), respectively. Pts were heavily pre-treated (1 taxane: 55.5%, ≥ 2 taxanes: 27.8%; 1 ARPI: 37.3 %, ≥ 2 ARPIs: 58.9%). Disease burden at the time of tx start was extensive, as indicated by sites of metastases (for tumor patterns see table). Median OS (mOS) from the start of PSMA-RLT was 9.8 mos (95% CI: 8.6, 11.3). In the US cohort (N = 857, med age = 71, IQR: 65, 78) med time from initial dx and mCRPC dx to index tx was 49 mos (IQR: 27, 99) and 16 mos (IQR: 10, 25), respectively. 88.9% of pts received prior tx with 1 taxane and 11.1% with ≥2 taxanes, 65% with 1 ARPI and 35% with ≥ 2 ARPIs. Med OS for US patients was 8.5 mos (95% CI:7.6, 9.1). Conclusions: This study provided the unique opportunity to describe real-world outcomes for late stage mCRPC patients treated with PSMA-RLT. The study design did not allow for a direct comparison between the two cohorts. Qualitatively, UKE patients were heavily pre-treated with extensive disease burden at the start of PSMA-RLT. Nevertheless, the study demonstrated promising rw outcomes for patients with mCRPC under PSMA-RLT. Future work, including the direct comparison of PSMA-RLT versus other tx in a similar disease setting, will help further characterize the benefit of this novel tx in practice. [Table: see text]
Subgroup analyses of efficacy outcomes by baseline tumor size in the phase 3, open-label CLEAR trial.
Authors: Viktor Grünwald, Robert J. Motzer, John B. A. G. Haanen, Manuela Schmidinger, Michael D. Staehler, Jeffrey C. Goh, Eric Voog, Miguel Ángel Climent, Saby George, Joseph E. Burgents, Ran Xie, Jodi McKenzie, Camillo Porta
Journal: Journal of Clinical Oncology (2024)

364 Background: In the primary analysis of the phase 3 open-label CLEAR trial, lenvatinib + pembrolizumab (L+P) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared with sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC) (Motzer NEJM 2021). Outcomes were further corroborated by results of the final prespecified analysis of CLEAR (Motzer ASCO 2023). We report efficacy outcomes per baseline tumor size in the L+P arm of CLEAR. Methods: 1069 treatment-naïve pts with aRCC and a clear-cell component were randomized (1:1:1) to: L 20 mg PO QD + P 200 mg IV Q3W; or L 18 mg + everolimus 5 mg PO QD; or S 50 mg PO QD (4 wks on/2 wks off). Stratification factors included geographic region and MSKCC prognostic risk group. IMDC risk groups (derived programmatically) are presented in this analysis. Efficacy outcomes were evaluated by quartiles of baseline sums of diameters of target lesions. Tumor assessments were performed by independent imaging review per RECIST v1.1. Results: Pts were grouped into 4 categories: ≤Q1 (34.72 mm), &gt;Q1 - ≤Q2 (60.06 mm), &gt;Q2 - ≤Q3 (108.56 mm) and &gt;Q3 per baseline tumor sizes (Table). For pts with ≤Q1 baseline tumor sizes, 40.7% and 58.0% were in the favorable and intermediate + poor IMDC risk subgroups, respectively. For pts with &gt;Q3 baseline tumor sizes, 6.3% and 93.8% were in the favorable and intermediate + poor IMDC risk groups, respectively. Median OS, PFS, ORR, complete response (CR), partial response (PR), and near-CR (PR with maximum tumor shrinkage ≥75%) by baseline tumor size categories are in the Table. Conclusions: In CLEAR, clinically meaningful efficacy with L+P was observed across pts with aRCC irrespective of their baseline tumor sizes. These results support the use of L+P for the 1L treatment of aRCC across pts with both low and high baseline tumor size. Clinical trial information: NCT02811861 . [Table: see text]
Prostate-specific membrane antigen expression in endothelial cells of renal tumor-associated neovasculature and risk of recurrence for renal cell carcinoma.
Authors: Tadahiko Kikugawa, Keito Kagimoto, Ryuta Watanabe, Noriyoshi Miura, Takashi Saika
Journal: Journal of Clinical Oncology (2024)

377 Background: PSMA is highly expressed in prostate epithelial cancer cells and used not only for diagnostic but also for therapeutic purposes. Despite its name, PSMA is not specific in prostate cells and is also expressed endothelial cells within the neovasculature of other tumors including renal cell carcinoma. PSMA is particularly the correlation of increased PSMA expression with prostate cancer aggressiveness, but is unknown in renal cell carcinoma patients. Here we estimate whether PSMA expression in endothelial cells of renal tumor-associated neovasculature is associated with pathological venous invasion and prognosis for patients after renal tumor surgery. Methods: A total of 45 patients who underwent radical or partial nephrectomies performed at our institution were included in this study. We investigated pathological venous invasion and PSMA expression in tumor-associated vessels around renal cell carcinoma by immunostaining using removed tumor tissue. The PSMA immunostain was evaluated in tumor-associated vessels according to the staining intensity and divided into three groups: weak, moderate, and strong, respectively. Results: Higher PSMA expression group is increased the percentage of patients with histologically observed venous invasion. The level of PSMA immnostain were detected in 18 cases at weak, 11 at moderate, 16 at strong. Ten patients after surgery had recurrence during the observation period, and the prognosis was worse in the group with strong PSMA expression in tumor-associated vessels around renal cell carcinoma. Conclusions: PSMA expression in endothelial cells of renal tumor-associated neovasculature may be a novel prognostic factor for renal cell carcinoma.
Diversity among editorial boards of genitourinary oncology journals.
Authors: Zhaohui Arter, Nataliya Mar, Arash Rezazadeh, David Joseph Benjamin
Journal: Journal of Clinical Oncology (2024)

481 Background: Several studies have evaluated the ethnic and gender diversity among editorial boards of academic journals in science and medicine, and revealed disparities among representation of historically underrepresented groups. However, the diversity among editorial boards in the field of genitourinary oncology remains unclear. Methods: Using the master journal list from Clarivate, we identified academic journals with a dedicated or primary focus in genitourinary cancers. We then identified the list of editorial board members on each journal’s website. We evaluated economic diversity based off each editor’s country of origin, and classified countries as high income based off World Bank listing for the 2024 fiscal year. We confirmed gender from each editor’s self-reported gender on his or her academic profile. Results: We identified 7 journals with a focus in genitourinary cancers. Among these journals, a total of 485 editor positions were identified, with 397 men (81.86%) and 80 women (16.49%). The gender of 8 individuals (1.65%) could not be confirmed. 28 editors (5.77%) were from countries not identified as high-income countries per World Bank criteria. Conclusions: There are disparities in country of origin among editors of genitourinary oncology journals, with a small proportion of editors originating from countries classified as middle- or low-income. [Table: see text]
Long-term outcomes for patients with radiorecurrent prostate cancer treated with salvage combination IMRT and brachytherapy.
Authors: Michael J. Dattoli, Arvind B. Soni, Lauren Yanthis, Jone Fay, Gregory Lawrence
Journal: Journal of Clinical Oncology (2024)

125 Background: Effective salvage of locally recurrent prostate cancer after definitive radiation is typically disappointing and may be associated with significant complications. Methods: 133 consecutive prostate cancer patients (ages 46-78) with biopsy proven local failures were treated between 2001 and 2021 and followed, prospectively with respect to clinical and/or biochemical failure and toxicity. Pre-recurrence treatment had consisted of external beam radiation (Photons: 102 patients, Protons: 16 patients) or iodine 125 brachytherapy (15 patients). Prior to salvage treatment, an extensive workup ruled out gross extracapsular extension or distant disease spread. Salvage treatment consisted of an attenuated dose of IMRT to the prostate (1200 cGy/8 fxs) followed by an attenuated Pd-103 brachytherapy boost (median 9000 cGy) within 24-72 hours. The Pd-103 isotope was used given its steep radial dose fall off, thereby reducing dosage to previously irradiated surrounding tissues. All patients were treated with a median 6 months of androgen deprivation. Mean pretreatment PSA was 5.9 ng/mL (range 1.9 - 22.3, median 3.9) with 64 patients having a Gleason score of greater than or equal to 8, 61 patients having a Gleason score of 7, and 8 patients having a Gleason score of 6. Follow-up from date of implant ranged from 3 years to 20 years (median 14 years). Biochemical failure was defined using PSA greater than or equal to 0.2 and nadir +2 at last follow up. All biochemically failing patients underwent transperineal prostate biopsies (median 18 cores). Results: Overall, 72% (96/133 patients) have maintained a PSA less than or equal to 0.2 ng/mL at median 14 years. Biochemical freedom at 5 years was 91%. PSA prior to re-treatment was highly predictive of distant progression with no patient having a PSA greater than 15 being successfully salvaged. Prostate biopsies of failing patients revealed only 3 local failures. 4 patients required post-implant TURP and 2 TURP patients developed low volume stress incontinence, 2 patients developed urethral strictures which were successfully treated to resolution. No patient has developed rectal ulceration, prostatic-vesicorectal fistula, or chronic cystoproctitis. Conclusions: This study helps strengthen the rationale for the use of Brachytherapy-based regimens in the treatment of radiorecurrent prostate cancer. In view of its even steeper radial dose falloff, we are currently exploring the advantages of Cs-131 in these patients.