bluuebunny/crossref_metadata_2025 huggingface dataset:
Early detection of recurrent prostate cancer using 18F-DCFPyL PET/CT PET/CT in patients with minimal PSA levels.
Authors: Sonni Ida , Nickols Nicholas George , Niknam Katelyn , Berenji Gholam Reza , Schaffer Derace , Montagut Louis , Sjöstrand Karl , Anand Aseem , Rettig Matthew
Published: February 2025

344

Background:
PSMA PET imaging is a highly sensitive and specific imaging tool for detecting prostate cancer, especially in biochemical recurrence (BCR). This has led to growing interest in utilizing PSMA PET for patients with minimally detectable PSA levels following definitive treatment as conventional imaging rarely localizes recurrent disease in this range, potentially delaying diagnosis and appropriate management. However, there is limited literature on the detection rate of 18F-DCFPyL at very low PSA levels in the BCR setting.
Methods:
This is a pooled retrospective analysis of patients from investigator-initiated trials at West Los Angeles Veterans Affairs and the phase III CONDOR trial with minimal PSA levels. Patients included had 18F-DCFPyL PET/CT at minimal PSA values (0.05 to 0.5 ng/ml). BCR was defined as rising PSA and patients were included irrespective of prior conventional imaging findings. The PET/CT scan reads were assisted by the automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) platform. The results were verified by an experienced and independent nuclear medicine physician. Primary analysis focused on the detection rate defined as the number of patients with positive PSMA lesions relative to total number of patients with BCR.
Results:
In total 129 patients were identified, 36 with PSA levels ranging from 0.05 to 0.2 ng/ml, and 93 with PSA levels >0.2 to 0.5 ng/ml. The site of positive findings, the intensity and volume of uptake in the 18F-DCFPyL PET/CT scan are detailed in the table below.
Conclusions:
18F-DCFPyL PET/CT demonstrates high detection rate for recurrent prostate cancer even in patients with minimally detectable PSA levels, highlighting its potential as a valuable tool in early identification of metastatic disease. These findings suggest that current thresholds for initiating PSMA PET/CT imaging in BCR patients may need reconsideration to optimize early detection and subsequent clinical management. Further studies are necessary to refine guidelines and assess the cost-effectiveness of incorporating PSMA imaging at very low PSA levels.

0 – 0.2 (N=36)
0.2 – 0.5 (N=93)

Total Detection Rate
13 (36%)
47 (51%)

Prostate Bed

3 (8%)
4 (4%)

Lymph Node Only

5 (14%)
29 (31%)

Lymph Node and Bone

12 (33%)
39 (42%)

Bone Only

8 (22%)
14 (15%)

Visceral (Lung or Liver)

1 (3%)
10 (11%)

Total SUVmean
3.8
4.2

Total SUVmax
10.9
12.4

Total disease volume (mean)
4.9 ml
1.9 ml
GLP-1 analogues and prostate cancer incidence: A systematic review and meta-analysis.
Authors: Gong Selena , Yu Eric , Chakkal Tanvir , Shamsheri Tahmina , Abumustafa Yousef , Lavoie Declan CT , Leong Darryl , Cirne Filipe , Baro Vila Rocio Consuelo , Dallegrave Cavalli Germano , Aldarraji Ahmed
Published: February 2025

374

Background:
Preliminary evidence from preclinical and observational data suggests that GLP-1 receptor agonists (GLP-1RAs) may reduce prostate cancer (PCa) incidence. We aimed to assess the effects of GLP-1RAs on PCa risk.
Methods:
Embase, Medline, Web of Science, and Cochrane databases were searched from inception to identify phase III randomized controlled trials (RCTs) comparing a GLP-1 RA with placebo/non-GLP-1 RA regimens. The primary outcome was incidence of PCa. A Mantel-Haenszel random-effect meta-analysis was carried out to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for the occurrence of PCa among male participants.
Results:
Of the 27,103 abstracts identified, 56 trials including 59,334 male participants were included. Eligibility included type 2 diabetes mellitus in 48 studies, obesity in 7 studies, and heart failure in 1 study. The GLP-1 RA’s studied included liraglutide (18), semaglutide (13), dulaglutide (6), albiglutide (6), lixisenatide (5), exenatide (4), and others (5). One study included both liraglutide and semaglutide as interventions. Follow-up durations ranged from 12 weeks to 260 weeks (5 years), with a mean of 72.5 weeks (standard deviation = 50.85). The pooled incidence of PCa was 0.55% (150 of 27,126) for the control group and 0.46% (148 of 32,208) for the GLP-1 intervention group. The pooled RR of PCa incidence with all GLP-1 RAs compared to controls was 0.86 (95% CI: 0.69-1.06, p=0.16).
Conclusions:
There were proportionally fewer incident PCa cases among GLP-1 RA recipients as compared with control. However, this did not achieve statistical significance. Trials were limited in duration and by the lack of pre-specification of this outcome. Further research is needed to evaluate whether GLP-1 RAs have activity against established PCa.
The impact of the Area Deprivation Index on immunotherapy outcomes in metastatic renal cell carcinoma (mRCC).
Authors: Feinaj Ardit , Rhinehart Dena , Zahurak Marianna , Linville Laura Meili , Singla Nirmish , Lansey Dina , Markowski Mark Christopher , Carducci Michael A , Elias Roy , Ged Yasser
Published: February 2025

445

Background:
The treatment landscape of mRCC has evolved in recent years with the advent of immune-checkpoint inhibitors (ICIs). The Area Deprivation Index (ADI) measures social determinants of health geographically, ranking neighborhoods by socioeconomic disadvantage. However, there are limited data on ICIs outcomes in relation to ADI. We investigated the association between ADI and clinical outcomes of ICI in mRCC.
Methods:
We conducted a retrospective analysis of 560 mRCC patients (pts) treated at our institution from 2013 to 2024. Eligibility included metastatic disease and ICI treatment at any line. Baseline characteristics and treatment outcomes were obtained from chart review. The ADI scores were calculated by entering the pts addresses at the time of starting ICI into the Neighborhood Atlas. The results were categorized into four quartiles (1st:1-25, 2nd: 26-50, 3rd: 51-75, 4th: 76-100), with higher scores indicating greater deprivation. Overall survival (OS) and progression-free survival (PFS) were calculated from the start of ICI by the Kaplan-Meier method. Immune-related toxicity was assessed across ADI groups. Univariate and multivariate analyses were performed to assess the impact of ADI on survival outcomes, controlling for confounding variables.
Results:
Our analysis included 287 eligible mRCC pts. Most pts were male (n=208, 72%) with a median age at ICI start of 63 years. Primary histology was clear cell in 238 pts (83%). Pts were 79% White, 13% Black, and 7% other races. Most pts received ICI in the first line (65%) and in combinations (71%). Based on ADI quartiles, 46.3% were in the 1st, 32.4% in the 2nd, 15.3% in the 3rd, and 6% in the 4th quartile. Survival analyses revealed that pts in the highest ADI quartile (4th) had significantly shorter OS (p=0.01) and PFS (p=0.03) compared to those from areas with lower ADI scores. Multivariate analysis confirmed shorter OS in the highest ADI quartile (HR 2.39 [1.32, 4.31], p=0.004). No significant differences in immune-related toxicity rates were observed. Univariate analysis of the continuous ADI values revealed a correlation of higher scores with shorter OS (HR 1.24 [95% CI: 1.06-1.46] p=0.008) and PFS (HR 1.17 [95% CI: 1.02-1.35] p=0.03).
Conclusions:
Despite landmark improvements in survival outcomes with ICIs in mRCC, pts in deprived areas continue to experience poorer outcomes, highlighting the need for targeted interventions to enhance access to care and to better understand how neighborhood deprivation impacts overall health both prior to diagnosis and over the course of care. Further pan-cancer studies are essential to validate these findings.
State of the genitourinary medical oncology workforce in the United States, 2024.
Authors: Benjamin David Joseph , Rezazadeh Arash
Published: February 2025

446

Background:
There are approximately 13,400 oncologists engaged in patient care in the US as of 2022. As the field of medical oncology becomes subspecialized in not only academic but in community settings, it remains unclear unknown how many practicing oncologists identify as genitourinary medical oncologists.
Methods:
Using lists for the top fifty hospitals per state as ranked by US News & World Report, we identified practicing medical oncologists. We then identified those with a primary (100%) or predominant (50% or greater) areas of clinical focus in genitourinary oncology. We collected data on gender, race/ethnicity, and medical education.
Results:
We identified a total of total of 451 genitourinary medical oncologists in the United States. Of these, 399 (88.5%) practice in academic settings while 52 (11.5%) practice in community-based hospitals. 327 (72.5%) genitourinary medical oncologists are male, while 124 (27.5%) are female. 17 GU oncologists (3.8%) are from underrepresented minority groups in medicine. 321 oncologists (71.2%) were trained at US medical schools. 76 (16.9%) identified a particular organ (prostate, bladder, kidney, or testicle) as a clinical or research area of focus. The Northeast US had the most GU oncologists (n=150), followed by the South (n=129), West (n=97), and Midwest (n=75). Seven US states have no genitourinary medical oncologist.
Conclusions:
Medical oncologists with a primary or predominant focus in genitourinary cancers make up 3.4% of the medical oncology workforce in the US. Seven (14%) of US states do not have a self-identified genitourinary medical oncology expert. Gender and racial/ethnic disparities are present among the genitourinary medical oncology workforce.

State of the workforce among genitourinary medical oncologists in the US.

Number
Male
Female
Underrepresented Minorities
Focus

Academic
399
285
114
15
Prostate (39), bladder (14), renal (18), testicular (2)

Community
52
42
10
2
Renal (1), Prostate (2)

Total
451
327
124
17
Effects of integrating palliative care on the uptake of advance care planning among elderly patients with advanced genitourinary cancers.
Authors: Chansriwong Phichai , Tiyanont Tanin , Semsarn Siriporn , Thokanit Nintita Sripaibookij
Published: February 2025

49

Background:
Integrating palliative care (PC) into oncology has been demonstrated to significantly enhance the quality of life for these patients and facilitating patient decision-making, particularly concerning advance care planning (ACP). ACP is a structured process that ensures patients' values and preferences regarding the end-of-life care are respected, and frequently results in the completion of advance directives (AD). This study aims to evaluate the impact of PC on the uptake of ACP among patients with advanced GU cancers.
Methods:
A retrospective analysis was conducted using a claims database from Ramathibodi Hospital, encompassing elderly cancer patients who had a medical claim for death between Jan1, 2016, and Dec31, 2021 included 1,013 patients, with 532 males, and a mean age of 72.37 years (60.5-99). Among these, 215 patients (21.2%) received integrated palliative care (PC). 102 patients with GU malignancies, including 44 with TCC, 36 with prostate cancer, 22 with RCC. Of these, 22 patients (21.6%) were treated with PC. The primary outcomes measured were the completion rates of ACP and AD. Secondary outcomes included the utilization of treatments in the 6 months preceding death. Comparative analyzes were performed between the PC and UC groups to assess the impact of PC on these outcomes.
Results:
Regarding ACP, 78.9% of patients in the UC group engaged in ACP, with a median time of 4.5 days (range: 0-324 days) before death. In contrast, 100% of patients in the PC group engaged in ACP, with a median time of 259.7 days (range: 0-2,077 days) before death. 46.5% of patients in the PC group completed AD, whereas no patients in the UC group completed AD. Patients receiving palliative chemotherapy within 30 days before death were significantly lower in the PC group, with an odds ratio of 3.30 (P < 0.001). In the 6 months preceding death, the PC group exhibited significantly lower ER visits (P = 0.011), inpatient admissions (P < 0.001), and total hospital visits (P = 0.002) compared to the UC group.
Conclusions:
Integrating palliative care into the oncology treatment framework significantly improves the uptake of ACP among patients with advanced GU cancers. This comprehensive approach not only reduces the utilization of aggressive treatments near the end of life, but also enhances the alignment of medical care with patients' values and preferences. Clinical trial information:
COA. MURA2023/258
.
Bone metastases and use of bone protective agents (BPA) for metastatic renal cell carcinoma (mRCC): A contemporary national real-world analysis.
Authors: Millan Braden , Ghosh Sunita , Basappa Naveen S. , Wood Lori , Bhindi Bimal , Pouliot Frederic , Breau Rodney H. , Finelli Antonio , Bansal Rahul K. , Graham Jeffrey , Bjarnason Georg A. , Bosse Dominick , Castonguay Vincent , Winquist Eric , Heng Daniel Yick Chin , Kollmannsberger Christian K. , Lalani Aly-Khan A.
Published: February 2025

490

Background:
Bone Metastases (BM) occur in approximately 30% of mRCC patients (pts) with evidence suggesting that they portend a worse prognosis. Systemic therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICI) are felt to be active in these pts, with radiation therapy (RT) often employed for BM-directed treatment. The evidence for and use of BPAs, such as bisphosphonates and denosumab, is limited in the current ICI era. We investigated the outcomes of mRCC pts with BM and use of BPA in a contemporary real-world cohort.
Methods:
We analyzed data collected from the prospectively maintained, multi-institutional Canadian Kidney Cancer Information System (CKCis). Patients with clear cell mRCC treated between January 2011-June 2023 were included. Outcomes were compared between BM+ and BM- pts using Cox proportional hazards models. Kaplan-Meier estimates were used to assess time to treatment failure (TTF) and overall survival (OS) adjusted by IMDC criteria.
Results:
Of 2,307 patients with clear cell mRCC, 893 (39%) had BM+, of whom 691 (77%) underwent RT, and 139 (16%) received a BPA. Median follow-up was longer for BM- patients (34.6 vs 29.1 mos). Significant differences were noted in Karnofsky performance status (> 80%: 84% vs 78%), IMDC risk group (intermediate/poor: 76% versus 82%) use of RT (35% vs 78%), and use of BPAs (2% vs 16%) between BM- vs BM+ pts (all p < 0.05). In our cohort, first-line treatment in BM+ pts was monotherapy TKI (67%), doublet ICI (20%), and combination TKI+ICI (13%). Median TTF was similar in BM- vs BM+ pts: 9.6 vs 8.6 mos (HR 0.92; 95% CI 0.91-1.02). However, median OS was higher in BM- vs BM+ pts: 57.6 vs 35.8 mos (HR 0.67; 0.58-0.76; p<0.0001); this was consistent irrespective of type of systemic therapy. In BM+ pts, those who did not receive BPAs had a lower TTF (7.9 vs 13.4 mos) and OS (34.0 vs 46.0 mos); however, these were not statistically different when adjusted by IMDC criteria (TTF HR 1.2; 0.95-1.51 and OS HR 1.12; 0.85-1.46). There was no significant difference in TTF (HR 0.89; 0.72-1.10) or OS (HR 0.94; 0.73-1.22) in BM+ pts selected to receive RT.
Conclusions:
BM remain a poor prognostic factor in mRCC in this contemporary cohort of patients. While BPA use was limited, we observed no improvement in TTF or OS in BM+ pts with their use. These data warrant further investigation of BPA in mRCC including assessment of SREs and potential complications.
Comparative survival outcomes of non-clear cell and clear cell renal cell carcinomas with indications for adjuvant pembrolizumab.
Authors: Musso Giacomo , Meagher Margaret F. , Yuen Kit L. , Ahdoot Aaron , Puri Dhruv , Dabbas Mai , Guer Melis , Birouty Natalie , Patil Dattatraya H. , Tanaka Hajime , Kobayashi Masaki , Fukuda Shohei , Montorsi Francesco , Briganti Alberto , Salonia Andrea , Capitanio Umberto , Larcher Alessandro , Fujii Yasuhisa , Master Viraj A. , Derweesh Ithaar H.
Published: February 2025

515

Background:
While immunotherapy has become first-line treatment for metastatic renal cell carcinoma in both clear cell (ccRCC) and non-clear cell (nccRCC) histologies, there has been limited investigation into adjuvant therapies for nccRCC in the context of high-risk localized RCC. As adjuvant Pembrolizumab is being more commonly employed for high-risk non-metastatic ccRCC, its application in nccRCC remains less understood. This study aims to compare survival outcomes between patients with high-risk localized ccRCC and nccRCC, focusing on cancer-specific survival (CSS) and overall survival (OS).
Methods:
Prospectively collected data from a multicenter database, including University of California San Diego Health (USA), IRCCS San Raffaele Hospital (Italy), Emory University Hospital (USA) and Tokyo Medical and Dental University (Japan), were retrospectively analyzed. Non-metastatic patients treated with surgery were included. The cohort was divided between nccRCC and ccRCC groups for descriptive and survival analyses, with the aim of comparing survival of the two groups according to subgrouping factors, specifically high-grade disease (G3-G4 or sarcomatoid features) at final pathology (HG) and locally advanced disease (pathological stage T3). Kaplan-Meier analyses (KMA) and Cox regression multivariable analyses (COX) were conducted to evaluate for cancer-specific survival (CSS) and overall survival (OS) and predictors of cancer-specific (CSM) and all-cause mortality (ACM).
Results:
With median follow-up of 58 months, a total of 5968 patients were analyzed. 4724 (79%) patients had a ccRCC while 1244 (21%) had a nccRCC. The nccRCC cohort comprised 923 (74%) papillary, 240 (19%) chromophobe and 81 (7%) variant histology patients. KMA comparing nccRCC high-grade (G3-G4; HG) tumors and ccRCC high-grade (HG) tumors showed no difference in 5-year CSS rates (nccRCC-HG 91% vs ccRCC-HG 88%, p=0.08) and 5-year OS (nccRCC-HG 79% vs ccRCC-HG, p=0.1). Comparing T3 stage tumors between nccRCC and ccRCC, KMA also showed similar 5-year CSS (nccRCC-T3 83% vs. ccRCC-T3 84%, p=0.05) and 5-year OS (nccRCC-T3 73% vs ccRCC-T3 73%, p=0.2). Cox regression for predictors of mortality showed that histology was not an independent predictor of CSM (p=0.17) and ACM (p=0.11).
Conclusions:
Although focus of most RCC adjuvant therapy clinical trials has been on ccRCC, aggressive features in nccRCC patients yield similar 5-year cancer-specific and overall survival rates. This study highlights the need for further clinical trials to evaluate efficacy of adjuvant systemic therapy in the setting of unfavorable groups of non-clear cell RCC.
Cadonilimab (anti-PD-1 and CTLA-4 bispecific antibody) combined with axitinib for the first-line treatment of advanced or metastatic non-clear renal cell carcinoma: A prospective, single-arm, phase Ib/II study.
Authors: Hu Xu , Zhao Fengnian , Chen Yuntian , Zhao Junjie , Shi Yifu , Tang Yanfeng , Wang Yongquan , Zhang Xingming , Liang Jiayu , Zhao Jinge , Chen Junru , Wei Qiang , Li Xiang , Liu Jiyan , Chen Ni , Shen Pengfei , Yao Jin , Sun Guangxi , Liu Zhenhua , Zeng Hao
Published: February 2025

544

Background:
Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of all renal cell carcinoma (RCC) and lacks standards of care. More recent data suggests the efficacy of anti-PD-(L)1 plus anti-CTLA-4 and immune checkpoint inhibitors combined with tyrosine-kinase inhibitors in the RCC. Cadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. Here we explore the efficacy and safety of cadonilimab in combination with axitinib in patients with advanced or metastatic nccRCC.
Methods:
Eligible patients had histologically confirmed advanced or metastatic nccRCC who had not previously received systemic therapy. Patients received cadonilimab (10 or 15 mg/kg q3w in phase Ib, and 10mg/kg q3w in phase II) in combination with axitinib (5mg bid) as first-line treatment until disease progression or intolerant to treatment. The primary endpoints were safety and objective response rate (ORR; RECIST v1.1). This study is registered with ClinicalTrials.gov, NCT05808608.
Results:
As of October 1, 2024, 26 patients were enrolled, median follow-up was 5.1 months (0.6-10.7 months). Twenty patients were available for efficacy assessment. Confirmed ORR was 55% (11/20), and disease control rate (DCR) was 95% (19/20). The median progression-free survival (PFS) was not reached. All patients experienced treatment-related adverse events (TRAEs), grade≥3 TRAEs occurred in 12 (46.2%) patients.
Conclusions:
Cadonilimab combined with axitinib demonstrated promising antitumoral efficacy and manageable toxicities in patients with advanced or metastatic nccRCC. The trial is an ongoing study, and complete results are awaited after completion of the enrollment and longer follow-up. Clinical trial information:
NCT05808608
.
Cabozantinib as subsequent therapy to an immune checkpoint-based therapy in renal cell carcinoma, phase 2 interventional study (AT ASIA, KCSG GU21-02).
Authors: Lee Jae Lyun , Shin Sang Joon , Park Inkeun , Bae Woo Kyun , Yoon Shinkyo , Kim In-Ho , Chon Hong Jae , Shim Byoung Young , Kim Jin Young , Kim Jung Hoon , Park Joo-Hwan , Kim Il Hwan , Kim Miso , Park Kwonoh , Lee Hyo Jin
Published: February 2025

547

Background:
Immune checkpoint inhibitors (ICIs) have significantly advanced the treatment of advanced renal cell carcinoma (aRCC). However, many patients develop disease progression, underscoring the need for effective second-line therapies. The optimal sequencing after ICI-based treatment remains under investigation. This phase II study evaluates the efficacy and safety of cabozantinib in patients with aRCC who progressed on first-line ICI combination therapies.
Methods:
This multicenter, prospective, phase II trial enrolled patients with advanced RCC who had progressed after receiving either nivolumab plus ipilimumab (Cohort 1) or a PD-1/PD-L1 inhibitor in combination with a VEGFR-TKI (e.g., pembrolizumab plus axitinib or pembrolizumab plus lenvatinib; Cohort 2). Non-clear cell histology was allowed in Cohort 2. Eligible patients were treated with cabozantinib at standard dosing. The primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Results:
From September 2021 to August 2024, 88 patients (Cohort 1, n=49; Cohort 2, n=39) were enrolled across 13 institutions. The baseline International Metastatic RCC Database Consortium (IMDC) risk categories were as follows: favorable (15.9%), intermediate (71.6%), and poor (12.5%). Prior nephrectomy was reported in 42.0% of patients, and non-clear cell histology accounted for 20.5% of Cohort 2. After a median follow-up of 18.3 months (95% CI, 11.3–25.3), the ORR was 47.7%. Partial responses were observed in 51.0% (95% CI, 40.1–61.5) of patients in Cohort 1 (ICI-ICI) and 43.6% (95% CI, 30.5–56.8) in Cohort 2 (ICI-VEGFR-TKI). Stable disease was achieved in 43.2% of patients overall. The median PFS was 7.9 months, with a PFS of 9.2 months (95% CI, 6.6–11.8) in Cohort 1 and 7.1 months (95% CI, 6.7–7.6) in Cohort 2. No significant difference in OS was observed between the cohorts, with a 12-month OS rate of 65.2%. Safety analysis revealed no novel adverse events beyond the known cabozantinib toxicity profile, with grade 3/4 hypertension, hand-foot syndrome, and fatigue being the most commonly reported events.
Conclusions:
Cabozantinib demonstrated substantial efficacy as a second-line treatment for advanced RCC following progression on ICI-based therapies, with a tolerable safety profile. These findings reinforce cabozantinib as an important treatment option for patients progressing after ICI regimens. Clinical trial information:
NCT04714697
.
Survival outcomes among metastatic castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitor and docetaxel.
Authors: Hwang Yunji , Wheeling Travis , Hatfield Mark , Kim Christopher
Published: February 2025

57

Background:
Real-world evidence on treatment patterns and real-world overall survival (rwOS) are limited in metastatic castration-resistant prostate cancer (mCRPC) patients treated with prior androgen receptor pathway inhibitor (ARPI) and docetaxel treatment. The objective of the study was to describe distribution of ARPI switch or cabazitaxel and their rwOS in patients with mCRPC settings after ARPI and docetaxel treatment.
Methods:
The study analyzedConcertAI Patient 360 data with a prostate cancer diagnosis in US, derived from electronic health records and claims data between 1990 and 2023. Among the eligible adult mCRPC patients, the study population included patients who subsequently received ARPI switch or cabazitaxel in mCRPC setting. The patient number and distribution (%) by treatments and subgroups were summarized. The study used the Kaplan-Meier method to calculate rwOS (median, months; interquartile range, IQR) and rwOS rate (%) at 12, 24 and 36 months from the start date of ARPI switch or cabazitaxel (Index Date).
Results:
Among 945 mCRPC patients with prior ARPI and docetaxel treatment (median age: 72 years; white: 79%; baseline PSA ≥ 100 ng/mL: 41%), cabazitaxel was more commonly used (59%) compared to ARPI switch (abiraterone: 22%; enzalutamide: 19%). The rwOS was 13 months, and rwOS rates of the overall patients were 53%, 29% and 21% for at 12, 24 and 36 months, respectively. Patients with liver metastasis had 9 months of median rwOS, while patients without liver metastasis had 14 months.
Conclusions:
The relatively short OS demonstrated the unmet medical need in mCRPC patients who received multiple treatments including ARPI and taxane-based chemotherapy, warranting the development of more effective and innovative treatments extending patient survival.

Overall survival in metastatic castration-resistant prostate cancer patients treated with androgen receptor pathway inhibitor and docetaxel.

Total (N=945)
Months (IQR)

Median OS in total patients (Death, n=770; 81%)
13 (6 - 29)

Median OS in subgroup patients by liver metastasis

No
14 (6 - 30)

Yes
9 (5 - 20)

OS Rate

%

12 months
53

24 months
29

36 months
21

IQR= interquartile range; OS=overall survival.
Association between clonal hematopoiesis and survival after nephrectomy in patients with renal cell carcinoma.
Authors: Khandwala Yash , Ruthen Neil , Kotecha Ritesh R , Russo Paul , Coleman Jonathan , Reznik Eduard , Hakimi A. Ari
Published: February 2025

589

Background:
Clonal hematopoiesis of indeterminate potential (CH) is an age-related phenomenon marked by the clonal expansion of hematopoietic stem cells harboring somatic mutations in the absence of hematologic transformation. These mutations have been linked to worse all-cause mortality from both oncologic and cardiovascular-related risk. Recent pan-cancer studies have also found that CH is common in patients treated for solid tumors and may be associated with survival. We thus sought to characterize CH mutations and their associated clinical impact in patients with localized renal cell carcinoma (RCC) at our institution.
Methods:
Utilizing a single institutional database of patients who underwent targeted, next-generation sequencing of paired tumor and blood samples (MSK-IMPACT), we identified 311 patients who were diagnosed with localized RCC and underwent nephrectomy. CH mutations were called using a two-tiered filtering schema, requiring a variant allele fraction (VAF) in blood greater than twice that of tumor. Chi-square and Wilcoxon rank-sum tests were used to compare clinical characteristics by CH status. Cox-proportional hazards modeling was used to test the association between CH and survival time following nephrectomy, adjusting for age and presence of diabetes, coronary artery disease (CAD), chronic kidney disease, hypertension, and smoking. We performed separate analyses for patients older and younger than the median age of 56.8 years as these groups had distinct CH, survival, and comorbidity profiles.
Results:
We assessed variants in 341 genes within the MSK-IMPACT CH database for 311 patients (CH: 79 [25.4%], no CH: 232 [74.6%]) who had localized RCC and underwent a nephrectomy (partial: 114 [36.7%], radical: 197 [63.3%]). DNMT3A (26), PPM1D (7), and TET2 (4) were the most common CH mutations. Patients with CH were older (median age of 64.1 years [IQR: 54.6 to 72.3] vs. 54.8 years [46.1 to 63.5]; p < 0.001) and had higher incidence of CAD (8/48 [16.7%] vs. 12/263 [4.7%], p = 0.004). There was no difference in rates of diabetes, hypertension, or CKD. For patients older than the median age of 57 years, those with CH had a shorter median survival of 86 months [72 to 119] compared to 125 months [96 to NR] (p = 0.02). For patients younger than the median age, age and hypertension were significantly associated with survival time but not CH (p = 0.29).
Conclusions:
Our study reveals that CH is common in localized RCC patients and may be associated with worse survival especially in older patients. Given the possibility of confounding from other comorbidities, future efforts will focus on identifying the true attributable effect of CH on survival. However, CH clones have been shown to interact with tumor cells and may influence immune surveillance, potentially providing a molecular basis for these findings.
Association between PD-1 expression on tumor-infiltrating regulatory T cells and resistance to first-line nivolumab in advanced clear cell renal cell carcinoma: Insights from the HCRN GU16-260 clinical trial.
Authors: Mohanna Razan , Simsek Berkay , El Ahmar Nourhan , Jegede Opeyemi , Matar Sayed , Paul Morgan , Nabil Laimon Yasmin , Roberti De Oliveira Gabriel , Delcea Andrew , Choueiri Toni K. , Braun David A. , Haas Naomi Balzer , Hammers Hans J. , Bilen Mehmet Asim , Stein Mark N. , Sosman Jeffrey A. , Wu Catherine J. , McDermott David F. , Atkins Michael B. , Signoretti Sabina
Published: February 2025

590

Background:
Inhibition of PD-1 signaling in regulatory T cells (Tregs) has been shown to enhance their immunosuppressive function. We previously demonstrated that high levels of PD-1 expression on tumor-infiltrating Tregs are associated with resistance to nivolumab (nivo) monotherapy in pretreated patients with advanced clear cell renal cell carcinoma (ccRCC) from the CheckMate-025 trial (Denize et al, 2024). Here, we aim to validate these findings in the first-line setting.
Methods:
Primary tumor tissues from patients with ccRCC (n=70) treated with first-line nivo in the HCRN GU16-260 clinical trial were analyzed using multiparametric immunofluorescence (IF). The percentage of tumor-infiltrating PD-1+ Tregs was quantified by image analysis. Associations with objective response rate (ORR) and progression-free survival (PFS) were evaluated using logistic and Cox regression models, along with Fisher’s exact test and log-rank test for statistical inference, as appropriate. The alpha level was set at 5% (one-sided).
Results:
In line with our previous findings, the percentage of PD-1+ Tregs, measured as a continuous variable, did not have a statistically significant association with PFS [HR = 2.62; p = 0.169] or ORR [OR = 0.72; p = 0.42]. Using an optimized cut-off based on the minimal p-value for ORR, patients with a high percentage (≥36%) of PD-1+ Tregs (8/70) experienced shorter median PFS (3.4 vs. 10.9 months; p = 0.001) and a trend toward lower ORR (12.5% vs. 43.6%; p = 0.093) compared to those with a low percentage (62/70).
Conclusions:
PD-1 expression on tumor-infiltrating Tregs is associated with worse outcomes to first-line nivo therapy in patients with advanced ccRCC, confirming our previous findings. These results highlight the therapeutic potential of targeting Tregs to overcome resistance and improve the efficacy of PD-1 blockade, which is currently being evaluated in a clinical trial (HCRN GU22-587).
Concordance of circulating tumor DNA and imaging surveillance in patients with urothelial carcinoma and renal cell carcinoma post-immunotherapy.
Authors: Meng Lingbin , Collier Katharine A. , Hasanov Elshad , Mortazavi Amir , Clinton Steven K. , Wang Peng , Zimmerman Danielle Elise , Bicer Fuat Bicer , Gauntner Timothy D. , Folefac Edmund , Monk Paul , Yang Yuanquan
Published: February 2025

597

Background:
Early detection of recurrence in urothelial carcinoma (UC) and renal cell carcinoma (RCC) may improve patient outcomes. Conventional imaging techniques may not identify early molecular relapses that precede clinical relapse. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for the early detection of disease relapse. This study aims to evaluate the concordance of molecular relapses by ctDNA and radiographic progression in patients with UC and RCC who are off immunotherapy due to intolerance of side effects or completion of treatment.
Methods:
We conducted a retrospective study of locally advanced/advanced UC and RCC patients who were treated at The Ohio State University James Cancer Hospital from November 2021 to September 2024. Patients who completed planned immunotherapy followed by imaging and ctDNA surveillance were included. ctDNA levels were measured using the Signatera tissue informed assay at intervals of 4 to 12 weeks. Imaging surveillance schedules were at the treating physician discretion. Patient demographics, clinical characteristics, and ctDNA levels were recorded and analyzed.
Results:
A total of 36 patients were included: muscle-invasive bladder cancer (MIBC, n = 10), metastatic urothelial carcinoma (mUC, n = 10), locally advanced RCC (n = 4), and metastatic RCC (mRCC, n = 12). The median follow-up was 39.5 weeks (range: 1–138 weeks), with a median age of 67.5 years (range: 41–83 years), and 72.2% were male. At the time of immunotherapy discontinuation, ctDNA was negative in all patients except one mRCC patient (ctDNA 0.95 MTM/mL). During surveillance, 9 patients (25%) - 5 mUC and 4 mRCC - became ctDNA-positive, of which, eight showed radiographic progression, while one mRCC patient (ctDNA 0.15 MTM/mL) did not. None of the 27 patients (75%) that continued to have negative ctDNA had radiographic progression. For the 8 patients with progression, the median time from stopping immunotherapy to ctDNA relapse was 17.5 weeks (range: 11–42 weeks). The median time from ctDNA relapse to imaging-confirmed progression was 22 weeks (range: 13–43 weeks). At progression, ctDNA levels ranged from 0.08 to 136.49 MTM/mL (median: 2.33 MTM/mL). Six of the 20 metastatic patients (30%) relapsed despite negative ctDNA at immunotherapy discontinuation.
Conclusions:
ctDNA positivity occurs much earlier and is highly concordant with radiographic progression in patients with locally advanced/advanced UC and RCC under post-immunotherapy surveillance. These findings suggest that ctDNA is a promising tool for early disease relapse detection in these patients. Further studies are warranted to validate these results and establish standardized ctDNA surveillance protocols.
Reduction of systemic chemotherapy by primary retroperitoneal lymph node dissection in low volume metastatic seminoma.
Authors: Pfister David , Paffenholz Pia , Rieger Constantin , Heidenreich Axel
Published: February 2025

626

Background:
Still, standard treatment of low-volume metastatic semimoma is either systemic chemotherapy or radiotherapy. Both options are associated with significant acute and long-term toxicities including mortality due to secondary malignancies in long-term follow-up. We calculated the number of potentially unnecessary chemotherapy cycles per hundred patients undergoing primary RPLND or Chemotherapy.
Methods:
In long-term follow-up of the COTRIMS-trial, 34 (12%) patients developed outfield relapses after a median follow-up of 41 months. All relapsing patients were cured by salvage PEB-chemotherapy. The base of our calculation are 12 recurrences on 100 Pts compared to 100 patients receiving chemotherapy upfront. Short term side effects of chemotherapy are from a historic patient cohort.
Results:
12 relapsing patients received 36 cycles of PEB instead of 300 cycles of chemotherapy if given as first-line treatment. Significant PEB-associated acute toxicities mostly affect haematoxicity with neutropenia in 4 and 37 patients, resp., and febrile neutropenia in 1.7 and 14 patients, resp.. Based on our previous studies (Paffenholz P et al., World J Urol 2019; 37:1907), thrombembolic venous or arterial events are expected in 1.2 and 0.8 , resp. versus 10 and 7 patients, resp.. Therapy associated mortality would be expected in 0.2 and 2 patients, resp.. No data on long-term toxicities are available.
Conclusions:
All patients with relapses after primary RPLND can be cured by salvage chemotherapy. The number of chemotherapy cycles can be reduced by 88% without impairing oncological efficacy if surgery is performed in an experienced reference center. Thus overall acute toxicity rate affecting patients quality of life and even treatment associated deaths can be reduced dramatically. Although the reduction of long-term toxicities associated with cytotoxic therapy cannot be anticipated today, we strongly recommend to include primary nsRPLND in the therapeutic armentarium of clinical stage IIA/B seminomas.
Management of relapsed stage I seminomatous germ cell tumor with retroperitoneal or pelvic only relapse.
Authors: Khalid Ahmed Bilal , Althouse Sandra K. , Hassoun Rebecca , Salous Tareq , Cary Clint , Masterson Timothy A. , Einhorn Lawrence H. , Adra Nabil , King Jennifer
Published: February 2025

630

Background:
For patients (pts) with stage 1 seminomatous germ cell tumor (SGCT) on active surveillance (AS), front-line therapy depends on the location and extent of relapse. We describe the characteristics and management of pts on AS with stage I SGCT with relapse in the retroperitoneum (RP) or pelvis only.
Methods:
The prospectively maintained Indiana University testicular cancer database was queried for pts with stage 1 SGCT on AS w/ RP or pelvic only relapse between 1990-2024. Pts were categorized into a chemotherapy, surgery, or radiation (XRT) group based on treatment at relapse. Comparisons between groups were done using Chi-square tests for categorical variables or Kuskal-Wallis test for continuous variables. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) using the log rank test to compare groups.
Results:
We identified 71 pts with stage 1 SGCT on AS w/ relapse in the RP or pelvis only. The median age at diagnosis was 37.2 yrs (range, 19.5-74.5). IGCCCG risk was good in all pts. At time of relapse, 37 pts (52.1%) were treated with chemo, 20 with surgery (28.2%), and 14 (19.7%) with XRT. The median time to relapse on stage I AS for pts treated with chemo was 9.5 months (0.84-91.7) compared to 19.9 months (1.6-60.2) with surgery and 13.1 months (4.6-48.8) with XRT (p=0.13). Chemo regimens used were BEP X 3 (62.2%), EP X 4 (21.6%), BEP X 4 (2.7%) and other (13.5%). 68 pts (95.8%) relapsed in the RP; 3 (4.2%) relapsed in the pelvis only. All 9 pts with lymph node (LN) size >5 cm were treated with chemo. In the 32 pts with LN size <3 cm, 12 (37.5%) were treated with surgery, 12 (37.5%) with chemo, and 8 (25%) with XRT. 11 total pts (15.5%) relapsed after front-line therapy and thus required multimodality treatment. This included 8 (21.6%) in the chemo group who relapsed; 2 out of 8 required RPLND while 6 were treated with salvage or high dose chemotherapy. 1 patient (5%) in the surgery group relapsed and required chemotherapy. In the XRT group, 2 pts (14.3%) relapsed; 1 was treated with salvage chemo and 1 with surgery. With a median follow-up time of 3.03 yrs (0-14.8), the 2-yr PFS for pts treated with chemo was 73.8%, surgery was 95%, and XRT was 92.3% (p=0.14). 2-yr OS was 100% for all treatment groups (p=0.58).
Conclusions:
In pts on AS with stage I SGCT w/ RP or pelvic only relapse, there was no difference in survival outcomes based on front-line therapy received. In this cohort of pts carefully selected for RPLND, the majority were cured with single-modality therapy; most of these pts had RP lymph nodes <3cm with a longer median time to relapse while on AS.
Racial disparities in incidence-based mortality and survival outcomes in testicular cancer in adolescent and young adults.
Authors: Ogedegbe Oboseh John , Ntukidem Olanipekun Lanny , Bai Sakshi , Olafimihan Ayobami Gbenga , Cheema Asfand Yar
Published: February 2025

650

Background:
Testicular cancer is the most common malignancy in males aged 15-35, with increasing incidence worldwide. Despite overall high survival rates, significant outcome disparities persist across race, socioeconomic status, and geographic location. Addressing these disparities is crucial to ensure equitable access to early diagnosis, treatment, and supportive care for all patients.
Methods:
Data from the Surveillance, Epidemiology, and End Results (SEER) 17 Research database program was utilized to obtain the annual percentage change (APC) in incidence of testicular cancer from 2000 - 2021 for patients aged 15 - 39 years (AYA group). Patient characteristics were expressed in proportions (%). The Kaplan Meier method was used to determine overall survival (OS) and cancer-specific survival (CSS). Cox regression was performed to determine predictors of survival. A p-value ≤0.05 was considered statistically significant.
Results:
A total of 19680 met our specified criteria and were included in our studies. We excluded cases with unknown race, and non testicular cancer cases. Our reference race was Hispanics. Compared to Hispanics. Non hispanic American Indian/Alaska Native had HR 1.696, (CI 1.290-2.229, p < 0.001, Non hispanic Asian/Pacific Islander had HR 0.880 (CI 0.712-1.087, p = 0.234), Non Hispanic Blacks had HR 1.608 (CI 1.267-2.039, p < 0.001), Non Hispanic Whites had HR 0.770 (CI 0.682-0.870, p < 0.001).
Conclusions:
Our study reveals significant racial disparities in testicular cancer survival outcomes with Non hispanic American Indian/Alaska Native and Non Hispanic Blacks having higher mortality risk. These findings highlight the need for targeted interventions to address survival disparities in testicular cancer across different racial and ethnic groups within the AYA demographic.
Utility of extended interval dosing of denosumab in patients with metastatic prostate cancer.
Authors: Schneck Stephanie , Hassoun Rebecca , Althouse Sandra K. , King Jennifer , Salous Tareq , Adra Nabil
Published: February 2025

68

Background:
Bone modifying agents, such as zoledronic acid and denosumab, are commonly used in patients (pts) with metastatic solid tumors to reduce the incidence of skeletal-related events (SREs). The FDA-approved administration schedule for both agents is every 4 weeks, however less frequent administration (i.e. every 12 weeks) is commonly observed in practice due to patient convenience. The efficacy and safety of these extended interval regimens is well-established for zoledronic acid, however there is little evidence available supporting this practice with denosumab.
Methods:
Pts with metastatic prostate cancer were evaluated for development of SREs during treatment with extended intervals of denosumab. 103 pts evaluated and treated at Indiana University Health between September 2019 and September 2024 were included in this analysis. A historical control group of pts receiving every 4-week dosing was used as comparison (1). SREs were defined as pathologic fracture, spinal cord compression, operation, or radiation to bone. Extended interval dosing is defined as an administration schedule >4 weeks apart on a consistent basis.
Results:
Median age at starting bone preserving agent was 70.6 years (range, 49.5-90). 24 pts (23.3%) had metastatic castration-sensitive prostate cancer and 79 pts (76.7%) had metastatic castration-resistant prostate cancer (mCRPC) at time of last follow-up. Incidence of SREs in all patients receiving extended interval denosumab was 23.3%. The incidence of SREs in patients with mCRPC receiving extended interval dosing was 26.6%. This compares favorably to historical data with incidence of SRE in the every 4 weeks dosing group at 35.9% (p=0.10). Median time to development of SRE was not estimable when all patients in the denosumab extended interval group were included in analysis. Median time to SRE in the mCRPC extended interval dosing group was 42.8 months and 20.7 months in the historical every 4-week dosing group (p<0.01). SREs identified for all patients receiving extended dosing interval denosumab were pathologic fracture (3, 2.9%), spinal cord compression (1, 1.0%), surgery (2, 1.9%), and radiation to bone (22, 21.4%).
Conclusions:
Our findings suggest that extended interval dosing of denosumab in patients with metastatic prostate cancer is not associated with an increased risk of development of SREs and may offer convenience for pts. Larger prospective studies are needed to validate these findings. 1. Fizazi K, Carducci M, Smith M, et al.
Lancet
2011; 377: 813–822.
Mental health monitoring in clinical trials for FDA-approved genitourinary cancer treatments: A decade review.
Authors: Jabbari Parnian , Teymouri Farzad , Yazdanpanah Omid , Mahadevan Aditya , Rezazadeh Arash , Benjamin David Joseph
Published: February 2025

696

Background:
The treatment landscape for genitourinary (GU) malignancies, including bladder, kidney, and prostate cancers, has evolved with several novel therapies approved in the past decade. The importance of mental health in patients with cancer is being more and more recognized in the past years. This study evaluates the monitoring of mental health and psychiatric symptoms in trials leading to FDA approvals for GU cancers.
Methods:
We comprehensively reviewed trial protocols and publications for FDA-approved GU cancer therapies from 2015-2024. For each approved therapy, we examined whether psychiatric side effects were monitored, the tools used, and the timing of assessments.
Results:
Of 42 trials for 31 approved treatments, 85% (36/42) monitored some psychiatric monitored psychiatric or mental health-related outcomes. EORTC QLQ-C30, EQ-5D-5L, and BPI-SF were the most common tools used for monitoring. However, 15% of trials did not assess mental health, and long-term follow-ups were inconsistent as described in the table. Depression and anxiety were the most evaluated symptoms. Nonetheless, the majority of the other psychiatric manifestations were not consistently assessed throughout trials.
Conclusions:
Psychiatric monitoring is present in many GU trials but remains inconsistent. Mental health assessments are typically part of broader quality-of-life evaluations rather than focused psychiatric tools. Future trials should adopt standardized psychiatric assessments to better manage patient well-being during treatment.

Psychiatric symptoms monitoring in FDA-approved GU cancer trials - 2015 to 2024.

Symptom
Assessed (%)
Baseline
Long-Term
Publications
Prostate
Kidney
Bladder

Depression
80%
Yes
Yes
No
Yes
Yes
Yes

Anxiety
80%
Yes
Yes
No
Yes
Yes
Yes

Insomnia
61%
Yes
Yes
Yes
Yes
Yes
Yes

Cognitive Impairment
38%
Yes
Yes
No
Yes
Yes
Yes

Irritability
38%
Yes
Yes
No
Yes
Yes
Yes

Emotional Lability
9%
Yes
Yes
No
Yes
No
Yes

Delirium
2%
No
No
No
No
Yes
No

Psychosis
2%
No
No
No
No
Yes
No