tbuckley/cabot-search huggingface dataset:
Prostate cancer risk groups by PSMA-PET PROMISE (PPP): Results from an international multi-center registry study.
Authors: Wolfgang Peter Fendler, Madeleine J. Karpinski, Sebastian Hoberück, Isabel Rauscher, Lena Unterrainer, Sazan Rasul, Anders Bjartell, Francesco Lanfranchi, Andrea Di Giorgio, Christian Helmut Pfob, Timo Soeterik, Karolien Goffin, Felix Kind, Jonathan Miksch, Jeremie Calais, Michael S. Hofman, Thomas A. Hope, Ken Herrmann, Boris A. Hadaschik, Kambiz Rahbar
Journal: Journal of Clinical Oncology (2025)

266 Background: We previously established prognostic nomograms of PSMA-PET standardized by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria in a large single-center cohort. Now, we reassess the PSMA-PET PROMISE (PPP) prognostic nomograms in a large international multi-center registry study with overall survival follow-up. Methods: We included patients with histologically proven prostate cancer who underwent PSMA-PET at 20 hospitals in Germany, Italy, Sweden, Netherlands, Belgium, Slovakia, Austria, United States and Australia between 2014 and 2021. PSMA-PET was standardized by molecular imaging TNM (miTNM). Total tumor volume in L, PSMA expression score and overall survival follow-up were obtained. The cohort was randomly split 2:1 into development and validation cohorts. In the development cohort we assessed PPP predictors and created visual and quantitative PPP nomograms based on Cox regression models with least absolute shrinkage and selection operator penalty for overall survival. Performance of both nomograms was measured in the validation cohort using Harrell´s C-index and calibration plots. Head-to-head comparison to the NCCN risk score was examined by ROC-curves. Results: We analyzed 6128 male patients (4075 development and 2053 validation) across all disease stages with 1915 (31.2%) reported deaths and median follow-up of 4.77 years [IQR 3.38-6.44]. Predictors in the visual PPP nomogram were distant metastases (extrapelvic nodal metastases [M1a], bone metastases [M1b; oligometastatic disease, disseminated or diffuse marrow involvement], and organ metastases [M1c]), PSMA expression score and total tumor lesion count. Predictors in the reassessed quantitative PPP nomogram were distant metastases (M1a, M1b, and M1c), tumor volume and PSMA expression score. C-indices (95% CI) in the validation cohort were 0.812 (0.794; 0.830) for the visual and 0.821 (0.805; 0.837) for the quantitative nomogram, respectively. For three-tier stratification (high, intermediate, low risk), accuracy of both PPP nomograms was superior when compared to the NCCN risk score (n=3638, visual: AUC 0.828 vs. 0.756; p&lt;0.0001 and quantitative: AUC 0.837 vs. 0.756; p&lt;0.0001). Conclusions: PSMA-PET PROMISE nomograms in an international multi-center study accurately stratify high vs. intermediate vs. low-risk groups for overall survival across all stages of prostate cancer and yield superior accuracy compared to the NCCN risk score. Follow-up continues in the PROMISE Registry (NCT06320223, promise-pet.org).
The prognostic impact of prostate-specific antigen at 6 months after post-prostatectomy radiotherapy: An individual patient data analysis of two NRG oncology randomized trials.
Authors: Osama Mohamad, David Michael Swanson, Alan Pollack, Himanshu Lukka, Alan Dal Pra, Ian S. Dayes, Andre-Guy Martin, Michael Greenberg, Alexander G. Balogh, Jeff M. Michalski, Peter Vavassis, Adam D. Currey, Robert Timothy Dess, Jason A. Efstathiou, Nirav S. Kapadia, Samir Patel, Belal Ahmad, Howard M. Sandler, Stephanie L. Pugh, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2025)

254 Background: We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) within 6 months of completion of salvage radiotherapy (RT) in patients treated with RT with or without hormone therapy (HT). Methods: Individual patient data were obtained from 2 randomized trials (NRG’s RTOG 0534 and RTOG 9601) evaluating salvage RT with or without HT. HT was either androgen deprivation therapy (ADT) for 4-6 months or bicalutamide for 2 years. The lowest PSA recorded within 6 months after RT completion was identified and categorized as ≤ or &gt;0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox proportional hazards regression was used to estimate hazard ratio (HR) with 95% confidence intervals to characterize the association of PSA within 6 months post-RT completion with OS and MFS while adjusting for age, Gleason score, trial, and HT use. Five-year MFS and 10-year OS rates were estimated using the Kaplan-Meier method. Results: Among a total of 2,373 patients, 1833 (77%) patients achieved a nadir PSA ≤0.1 and 540 (23%) did not. Among patients who did not get HT, 50% did not reach the milestone compared to only 6% of patients who got HT. PSA ≤0.1 ng/mL was associated with better OS (HR 0.27 [95% CI 0.12-0.6], p=0.001) and better MFS (HR 0.25 [95% CI 0.13-0.47], p&lt;0.0001). The interaction test showed that the improved OS/MFS in patients who achieved the nadir was more prominent in those who did not receive HT compared to those who received HT. Five-year MFS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 94% vs 81%, 92% vs 87%, and 91% vs 93%, respectively, based on PSA ≤ vs &gt;0.1. Ten-year OS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 87% vs 76%, 84% vs 84%, and 82% vs 83%, respectively, based on PSA ≤ vs &gt;0.1. Conclusions: PSA &gt;0.1 ng/mL within 6 months was prognostic for OS and MFS in patients treated with salvage RT in the post-prostatectomy setting. This finding allows better patient counseling and can guide clinical trial design for treatment intensification or de-intensification in patients receiving salvage RT.
Association between radiation therapy to the recurrence sites and oncological outcomes in patients who experienced local recurrence and/or pelvic lymph node metastases after radical cystectomy: A multicenter retrospective study.
Authors: Naoki Fujita, Shogo Hosogoe, Toshikazu Tanaka, Noritaka Ishii, Masaki Momota, Hiroyuki Ito, Takahiro Yoneyama, Chikara Ohyama, Shingo Hatakeyama
Journal: Journal of Clinical Oncology (2025)

788 Background: Local recurrence and/or pelvic lymph node metastases after radical cystectomy (RC) are often observed in patients with muscle-invasive bladder cancer (MIBC). Although chemotherapy and immune checkpoint inhibitors are the main treatment strategies in such patients, radiation therapy (RT) to the recurrence sites might be one of the treatment options. However, its effects on oncological outcomes remain unclear. Methods: This multi-institutional retrospective study included 106 patients who experienced local recurrence and/or pelvic lymph node metastases without distant metastases after RC. Patients were divided into two groups: patients who were treated with RT to the recurrence sites (RT group) and without (non-RT group). Multivariable Cox-proportional hazards regression analyses were performed to evaluate the effects of RT on cancer-specific survival (CSS) and overall survival (OS) after recurrence. Results: The median age at recurrence was 72 years, and the median follow-up period after recurrence was 13 months. Of the 106 patients, 65 (61%) received neoadjuvant chemotherapy (NAC) and 30 (28%) were treated with RT after recurrence. CSS and OS were not significantly different between the two groups ( P = 0.569 and P = 0.456, respectively). In univariable analyses, NAC, pure urothelial carcinoma, tumor grade, and lymphovascular invasion were significantly associated with CSS. Similarly, NAC, pure urothelial carcinoma, tumor grade, lymphovascular invasion, and pathological lymph node involvement were significantly associated with OS. After adjustment for these confounding variables, RT to recurrence sites was not significantly associated with prolonged CSS and OS (Table). Conclusions: RT to recurrence sites might have no effects on oncological outcomes in patients who experienced local recurrence and/or pelvic lymph node metastases after RC. Multivariable analyses for CSS and OS. CSS Factor P value HR 95% CI NAC Received 0.080 0.649 0.400–1.053 Pure urothelial carcinoma Positive 0.059 0.577 0.326–1.022 Tumor grade Grade 3 0.644 1.167 0.606–2.247 LVI Positive 0.003 2.407 1.353–4.283 Radiation therapy Positive 0.244 0.735 0.438–1.234 OS Factor P value HR 95% CI NAC Received 0.030 0.552 0.323–0.944 Pure urothelial carcinoma Positive 0.113 0.574 0.289–1.141 Tumor grade Grade 3 0.694 0.868 0.428–1.759 LVI Positive 0.005 2.438 1.305–4.556 Pathological N stage ≥ pN1 0.328 1.372 0.728–2.584 Radiation therapy Positive 0.161 0.652 0.359–1.186
Differences in incidence and clinicopathologic features of secondary bladder cancer after long-term follow-up of brachytherapy and radical prostatectomy for localized prostate cancer.
Authors: Kotaro Obayashi, Go Kimura, Hiroya Hasegawa, Hikaru Mikami, Jun Akatsuka, Hayato Takeda, Yuki Endo, Yuka Toyama, Hiroyuki Muramatsu, Katsuya Maebayashi, Shinichiro Kumita, Yukihiro Kondo
Journal: Journal of Clinical Oncology (2025)

381 Background: Although there studies have been reported that brachytherapy (BT) for prostate cancer is associated with an increased incidence of metachronous urinary bladder cancer (MBC), few studies have clarified differences in the clinicopathological features (CPF) of MBC between BT and prostatectomy (RP). We studied the risk and clinicopathological CPF of MBC between RP and BT groups in our hospital after long-term follow-up. Methods: Five hundred four patients treated with BT and 471 referred patients treated with RP between 2006 and 2017 in our hospital were reviewed. We compared the incidence of MBC and the CPF including the tumor number, location within the bladder, histology, and time from BT or RP to the MBC occurrence between BT and RP. The differences between the two groups were analyzed. Furthermore, in the BT group, the radiation dose distribution within bladder was estimated. Results: A total of 11 cases of MBC occurred in the BT group (2.2%) and 7 in the RP group (1.5%) after a median follow-up time of 107 months (13-209). The median time from initial treatments to the occurrences of MBC was 65 months (12-121) in BT and 100 months (4-126) in RP (p=0.469). Average tumor number was not significantly different between the groups (BT:1.4, RP:1.9, p=0.589). The tumor locations of MBC within the bladder for BT vs. RP were 9 vs. 1 in the lateral wall, 0 vs. 4 in the posterior wall, 0 vs. 3 in the dome, and 1 vs. 0 in the trigone. The incidence in the lateral wall was significantly higher in BT than in RP (p=0.001). Their median radiation dose of right wall (15.7±7.74Gy) and left wall (13.0±5.85Gy) showed no significant difference compared to the BT patients without MBC. There were 3 muscle-invasive cases in BT and 1 in RP (p=0.60). High-grade urothelial carcinoma occurred significantly more in BT (10 cases) than in RP (1 case) (p=0.001). According to the criteria, six MBC were judged as radiation-induced secondary bladder cancer. Conclusions: Long-term follow-up showed that the risk of MBC after BT was similar to that after RP. MBC after BT occurred significantly more frequently in the lateral wall and had a higher grade compared to those after RP.
Impact of COVID-19 pandemic on the treatment of prostate cancer in Brazilian public health system, comparing pre and post pandemic data.
Authors: Gustavo Franco Carvalhal, Guilherme Augusto Zulli, Igor Alexandre Protzner Morbeck, Daniel Herchenhorn, Andre Deeke Sasse, Rana R. McKay, Brent S Rose, Fernando Cotait Maluf, Fernando Sabino Marques Monteiro, Vinicius Carrera Souza, Andrey Soares, Denis L. Jardim, Diogo Assed Bastos, Dr. Paulo Sergio Lages, Elcio Firminiano, Douglas Andreas Valverde, Nicholas David James
Journal: Journal of Clinical Oncology (2025)

373 Background: During the COVID-19 pandemic resources from the Brazilian Public Health System (BPHS) were directed to the treatment of COVID-19. The impact of the pandemic on the treatment of prostate cancer in Brazil has not yet been rigorously evaluated. Methods: We compared the number of radical prostatectomies (RP), radiotherapy (RT), and hormonal (HT) and chemotherapy (CT) treatments from March 1st, 2020 to February 29th, 2022, with that of the two pre-pandemic years (March 1st, 2018, to February 28th, 2020). Additionally, we evaluated the post-pandemic period from March 1st, 2022 to February 28th, 2024. A large proprietary healthcare data science platform offered by TECHTRIALS was surveyed. Results: In the pandemic, 15,364RPs were performed in the BPHS, (U$14,271,297); there was a 23.3% reduction in the number of surgeries compared with the pre-pandemic years: 19,778RPs, (U$18,056,470). In the post-pandemic years 18,716 RPs were performed (U$ 18,373,781.92), an increase of 21.8% in those treated by surgery. In the pandemic, 34,922 men received RT (U$39,616,736), a 18.7% reduction in the number of patients as compared with the two pre-pandemic years, when 42,614 men were treated (U$44,148,190). In the post-pandemic years, 43,142 men received RT, an increase of 19% compared to the pandemic years (U$48,870,739.03). Regarding HT, 116,490 men were treated during the pandemic (U$74,834,615); in the pre-pandemic, 115,949 patients received HT (U$75,179,674). In the post-pandemic years, 127,602 men were treated with HT (U$80,078,824), an increment of 6.5% in cost and 10% in the number of patients treated compared to the pandemic years. As to CT for hormone-resistant disease, in the pandemic period 14,946 men were treated (U$23,402,947) compared with 12,695 men treated in the two pre-pandemic years (U$19,239,099). In the post-pandemic years 18,850 men were treated (U$33.571.073,40) an increment of 48.4% in number of patients treated and with an increase of 74% in costs compared to the pandemic period. Conclusions: During the pandemic years, there was a significant reduction of potentially curative treatments for prostate cancer in the BPHS. The number of systemic therapies increased, probably reflecting the policy of maintaining systemic therapies active during the pandemic. In the post-pandemic years, there was an increase in the number of systemic treatments, while RT and RP returned to a state very close to their pre-pandemic numbers. The impact of the COVID-19 pandemic on prostate cancer mortality in Brazil remains speculative.
Development of an ex-vivo platform to model immunotherapy in kidney cancer.
Authors: Shuchi Gulati, Wen-Hsin Chang, Aedric K Lim, Mamta Parikh, Nicholas Mitsiades, Marc Dall'era, Thenappan Chandrasekar, Philip Hsiao, Primo N Lara, Ching-Hsien Chen
Journal: Journal of Clinical Oncology (2025)

592 Background: The treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC) has evolved, with immune checkpoint inhibitor (ICIs) combinations contributing to improved survival. However, many patients remain unresponsive, highlighting the need for alternative strategies. While preclinical models have been instrumental in drug development, their translation to human applications often encounters challenges related to reproducibility. This emphasizes the urgent requirement for accurate, immunocompetent models of ccRCC that reflect human disease, identify effective immunotherapy regimens, and support reliable drug development. This study presents the development and characterization of a precision cut tissue slices (PCTS) model for primary ccRCC, capturing patient-specific heterogeneity. Methods: Twelve patients undergoing nephrectomy for primary ccRCC were consented. PCTS were obtained and co-cultured with autologous peripheral blood mononuclear cells (PBMCs) (5x10^5 co-cultured with one PCTS) and treated for six days. Treatment groups included: i) cabozantinib (cabo) alone, ii) cabo with cemiplimab (cemi, a PD-1 inhibitor), iii) cemi with fianlimab (fin, a LAG-3 inhibitor), and iv) the triplet regimen of cabo, cemi, and fin. The co-cultured PCTS were analyzed using H&amp;E staining and a Live-Dead stain to assess cell viability. Following co-culture, PBMCs were imaged and cytospun for histological analysis and characterized using multiplex immunofluorescence (MxIF). Results: Viability assessment of co-cultured PCTS indicated a significantly higher proportion of dead cells in the triplet-treated group (cabo+cemi+fin) compared with either doublet strategy. Additionally, the number of viable PBMCs, assessed six days post-co-culture, was also highest in the triplet group. Ongoing MxIF analysis aims to characterize the PBMCs further. Conclusions: This study characterizes an organotypic, patient-derived model based on the culture of tumor slices from primary renal cancers, where we have optimized for extended viability of PCTS in ex vivo culture. The drug treatment experiments conducted on the slices demonstrate the potential of PCTS as a preclinical tool for screening effective therapies for primary ccRCC, including immunotherapeutic approaches, which has been challenging in previous animal models. Our findings suggest that the triplet regimen (cabo+cemi+fin) may offer greater efficacy compared to the cabo+cemi or cemi+fin. Based on these results, an early-phase clinical trial to investigate the triplet in ccRCC patients is under development.
Assessing the impact of PTEN loss on outcomes in high-/very high-risk, advanced hormone-sensitive prostate cancer patients: Institutional retrospective study.
Authors: Tamara Jamaspishvili, Palak Patel, Mackenzie Bennett, Jonathan Bearden, Amber Bixby, Devashish Desai, Michel R Nasr, Gennady Bratslavsky, Hanan Goldberg, Alina Basnet
Journal: Journal of Clinical Oncology (2025)

260 Background: Inactivation of tumor suppressor gene, PTEN (Phosphatase and tensin homolog) by deletion or mutation occurs in between 15-20% of localized prostate cancers and up to 50% of castration-resistant prostate cancers. The series of studies has shown a robust correlation between the genomic loss of PTEN and its protein as assessed by immunohistochemistry (IHC). Dysregulation of PI3K/AKT/mTOR signaling pathway has been linked with adverse pathological features and poor oncological outcomes such as the development of disease recurrence, metastasis, and castrate-resistant prostate cancer (CRPC). Here, we aim to study the prognostic and predictive role of PTEN in relation to treatment outcomes in a newly developed retrospective institutional research cohort. Methods: The cases with genomic PTEN loss (FoundationOne CDx, n=190) and protein loss by IHC (BenchMark Ultra, Roche Diagnostics, n=273) were pooled together. A total of 311 patients (PTEN loss=84, PTEN intact=227) that had available clinical and pathological information, including follow-up, were used for downstream statistical analysis. Kaplan-Meier analyses and univariate and multivariate Cox proportional hazard models were used to assess the benefit of RP over definitive RT with or without androgen deprivation therapy (ADT) for high-risk localized cohort as well as the benefit of primary ADT with or without intensification in the patients experiencing the loss of PTEN. Results: Patients with PTEN loss were more likely to present with advanced-stage disease (Stage IV: 33% vs. 19%) and more frequently received RT+ADT (43% vs. 34%) in high-risk patients. In contrast, those with intact PTEN were more likely to undergo radical prostatectomy (34% vs. 28%). Although overall survival (OS) did not differ significantly between all groups (log-rank p=0.51), mortality was higher in the PTEN loss group (32% vs. 22%). There was also a trend toward earlier development of castration-resistant prostate cancer (CRPC) in patients with PTEN loss (log-rank p=0.16). Conclusions: PTEN loss in prostate cancer is linked to more aggressive disease, higher mortality, and earlier CRPC development, consistent with existing literature. Our findings suggest that high-risk/very high patients with PTEN loss may benefit from definitive RT-based treatment over surgery. The study is limited by its retrospective, smaller sample size and single-institution design.
Burden of cancer in metastatic renal cell carcinoma (mRCC).
Authors: Dena Battle, Meghan Griffith, Pavlos Msaouel, Sarah P. Psutka, Ulka N. Vaishampayan, Tian Zhang, Michael D. Staehler
Journal: Journal of Clinical Oncology (2025)

467 Background: Combination regimens and sequencing of multiple agents have significantly improved clinical outcomes for patients (pts.) with mRCC. We sought to assess the burden of mRCC on patients and interference with daily life. Methods: The survey was developed by the Kidney Cancer Research Alliance (KCCure), and broadcast between 09/24 and 10/24 to pts. via website, mailing lists and social media platforms. Results: Of 1167 respondents, 492 pts. had received systemic therapy for mRCC. Median age was 58.7 years (range 17.2 - 87.0), 83% were from the United States. 42% were on first line treatment, 30% second line, 13% third line, and 15% in fourth or later line. 69% were on systemic on therapy with evidence of disease, 10% were receiving treatment with no evidence of disease, 13% had discontinued treatment with no evidence of disease; 8% had discontinued treatment with evidence of metastatic disease. 45% of pts. take ≥7 prescriptions per day, 11% take ≥10 prescription medications per day. One-third (33%) of pts. are concerned they are taking too many medications. In the last year, pts reported seeing 4.24 (range 1-17) different types of doctors for cancer related care. In the last 90 days: 36% have gone to the emergency room, 20% more than once. 96% had blood drawn at least once, 35% had ≥5 blood draws. 95% had at least one clinic visit, 22% ≥5 clinic visits. 30% had ≥5 pharmacy visits. 23% have been hospitalized, 12% for ≥5 days. In the last year, 45% were hospitalized at least once, 52% more than once, 11% ≥5 times. Hospitalizations and visits to the emergency room were significantly correlated with a lower quality of life and higher NCCN distress score (p&lt;.001). 89% of pts think about cancer every day; 44% spend a few to several hours per day thinking about cancer. When asked how confident they feel about making plans, 33% feel completely confident making plans 6 months from now, 21% one year and 10% two years from now. Pts. with no evidence of disease are significantly more likely to rank their QOL as excellent (19%) compared to pts. with evidence of disease (4%), independent of treatment. Pts. who have discontinued treatment and still have evidence of disease rank their QOL as poor (17%). Conclusions: Pts. living with mRCC are physically and mentally consumed with cancer and disease management. mRCC disrupts fundamental daily activities, including eating, sleeping, and socializing. Pts. must routinely engage with the healthcare system, extensively managing scheduled and unscheduled appointments with multiple providers. Nearly all contemplate their cancer daily. More research is needed to improve care and alleviate disease burden in mRCC. Disruption of daily and routine activities. Activities Impacted by Cancer Frequency - Always or Often Eating a meal 37% Sleeping 38% Engaging with Friends 31% Grocery Shopping 25% Attending an Event 31% Buying Clothes 18% Traveling 43%