Human papillomavirus (HPV) is a well-established oncogenic virus implicated in the development of several epithelial cancers, most notably cervical, anogenital, and oropharyngeal carcinomas. In contrast, neuroendocrine neoplasms (NENs)—a heterogeneous group of malignancies arising from neuroendocrine cells across various organ systems—have not traditionally been linked to HPV infection. In this study, we performed extensive genomic and transcriptomic profiling to compare HPV-positive NENs to HPV-positive non-NENs across anatomical sites, aiming to uncover biologically and clinically actionable differences. HPV16- and HPV18-positive tumors were identified from 101,343 solid tumors profiled at Caris Life Sciences (Phoenix, AZ) with DNA and RNA sequencing. Prevalence of pathogenic mutations and copy number amplifications were calculated. Fisher’s exact/χ2 tests were applied appropriately with p-values adjusted for multiple comparisons (p < 0.05). HPV positivity was most frequent in cervical carcinomas (70

Copper 61 ( 61 Cu)–1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) prostate-specific membrane antigen (PSMA) imaging and therapy PET is safe and effective for the PSMA-targeted imaging of prostate cancer, opening new opportunities for constructing novel 61 Cu PET radiotracers for multiple malignancies.

Efforts to improve equity for women in oncology drug development have thus far focused on representation in clinical trials. However, it is now time to take the next step: ensuring trials capture outcomes that matter for women. Incorporating sex-specific analyses and biological variables can reveal differences in efficacy and toxicity and advance equitable care.

872 Background: There were 255 cancer drug approvals by the US Food and Drug Administration (FDA) between January 2020 and October 2024. Although genitourinary (GU) cancers (prostate, urothelial, renal and testicular) compromise some of the most prevalent malignancies, it is unclear how many of these drug approvals were intended for treatment of genitourinary cancers. Methods: Using the list of FDA cancer drug approvals, we identified approvals for GU cancer indications between January 2020 and October 2024. We collected data on tumor type, line of treatment, control arm, primary endpoint(s) as studied in the corresponding clinical trial, and phase of clinical trial. Results: We identified a total of total of 26 drug approvals for GU cancer indications (10.2%) among the total 255 drug approvals for all cancer types. Among these approvals, 12 were for urothelial, 9 for prostate, and 5 for renal. There was variation in the line of setting for each approval’s intended use as shown in the table. No cancer drug approvals were for testicular, penile or adrenal cancer. Most trials were phase III (n = 20), followed by phase II (n = 4) and then one each for phase IB/II and II/III. Overall survival was the most common endpoint (n = 10), followed by response rate and duration of response (n = 7), radiographic progression-free survival (n = 5), disease-free survival (n = 2), and one each for castration rate and metastasis-free survival. Conclusions: Drug approvals for GU cancers compromised approximately 10% of drug approvals by the FDA over the past five years. While OS continues to be the most commonly used endpoint in clinical trials, response rate and duration of response are commonly employed in BCG-refractory non-muscle invasive bladder cancer trials and radiographic progression-free survival in prostate cancer trials. Given the high incidence and mortality from GU cancers, continued drug development is warranted. Intended setting of use for genitourinary cancer drug approvals by tumor type, 2020-2024. Tumor Type Number Indication Urothelial 12 First line (n = 3), adjuvant (n = 1), maintenance (n = 1), BCG-refractory/UTUC (n = 4), second- or later-line (n = 3) Prostate 9 Hormone-sensitive (n = 2), hormone-resistant (n = 1), biochemical recurrence (n = 1), BRCA/HRD mutated (n =5) Renal 5 First-line (n = 2), adjuvant (n = 1), second- or later-line (n = 2) Testicular 0 No applicable Penile 0 Not applicable Adrenal 0 Not applicable 26

TPS4622 Background: Pts with muscle-invasive UC of the bladder or upper genitourinary tract who undergo radical cystectomy or nephroureterectomy are at high risk for cancer recurrence if residual pathologic advanced disease is identified at the time of surgery. Emerging data demonstrates that pts with minimal residual disease following curative-intent surgery, as detected by circulating tumor DNA (ctDNA), may be at a particularly high risk of UC recurrence. Adjuvant N has been approved post curative-intent surgery, with or without prior neoadjuvant chemotherapy (NAC), in pts with muscle-invasive UC at high risk of recurrence based on results of the CheckMate 274 study, which demonstrated a disease free survival (DFS) at 6 months of 74.9% with N versus 60.3% with placebo. SG is an antibody-drug conjugate with activity in UC. Evaluating intensification of adjuvant therapy in order to reduce the chance of metastasis development is of great interest. Methods: This is an IRB-approved, prospective, multi-center, single-arm phase 2 study of combination therapy with SG plus N. To be eligible, pts must have documented muscle-invasive UC, with variant and mixed histology allowed, except small cell. Pts must have undergone curative-intent surgery within 180 days prior to study therapy initiation and be radiographically free of metastasis. Pts who received prior NAC must have T2-T4 or node positive disease on surgical pathology, while those without NAC must have pathologic T3-T4 or node positive disease. Pts must also be ineligible or refuse platinum-based adjuvant chemotherapy. Additional selected eligibility criteria include creatinine clearance of at least 30 ml/min and adequate bone marrow function. If eligible for the study, pts will receive SG 7.5 mg/kg on day 1 and 8 combined with Nivolumab 360 mg on day 1 given every 21 days for 4 cycles, followed by single-agent Nivolumab 480 mg on day 1 given every 28 days for an additional 11 cycles. Use of growth factor support is allowed, as per institutional practice. Primary study endpoint is investigator-assessed DFS at 6 months. Secondary study endpoints include DFS, distant metastasis-free survival (MFS), overall survival (OS), incidence of grade 3 or higher adverse events, rate of ctDNA clearance in baseline ctDNA positive patients as well as exploratory biomarker analysis. The sample size calculation was based on a one-sided one sample test for exponential hazard rate when the probability of DFS at 6-months in the experimental group is 85% and in the historical control group is 75% in order to detect a hazard ratio of 0.565 with a power of 80% at a 0.05 significance level. Projected study accrual time is 24 months and per pt follow-up time is 36 months. Out of 23 anticipated pts, 3 have been enrolled to date since study activation in 11/2024. Clinical trial information: NCT06682728 .

Goal of the Review The objective of this review is to conduct a thorough examination of the current evidence regarding the correlation between dietary sugar intake and cancer risk. This will encompass the biological mechanisms, the diverse effects of various sugar types, and the potential implications for cancer treatment and dietary recommendations. Introduction Nutritional and epidemiological studies now focus much on the relationship between sugar intake and cancer. The data is still conflicting even if some studies imply that excessive sugar intake can help cancer develop by means of insulin resistance and chronic inflammation. Discussion Through processes such as insulin resistance, inflammation, and angiogenesis, dietary sugars can impact carcinogenesis. Fructose increases angiogenesis by VEGF overexpression while glucose stimulates cancer cell growth by the Warburg effect. Contradicting data on the contribution of sugar to cancer emphasizes the need of consistent research techniques to simplify these dynamics. Reducing added sugar consumption in cancer prevention and management is especially crucial given that sugar affects immune function and treatment resistance, which could lead to new therapeutic targets. Conclusion High sugar intake is linked to mechanisms such as the Warburg effect, insulin resistance, and chronic inflammation, which may contribute to cancer risk under specific conditions. However, the evidence is not universally conclusive, and additional large-scale, long-term research are required to better understand these processes. To help in cancer prevention and management, public health guidelines should emphasize reducing added sugar consumption and promoting a balanced diet rich in natural foods.

The recent withdrawal of sacituzumab govitecan for advanced urothelial carcinoma has revealed several implications, including concerns over a lack of remaining effective treatment options, reimbursement, supportive care measures (such as granulocyte-colony stimulating factor), dose reductions, and inconsistencies with related historical regulatory decisions.

Background: Combination therapy using an immune checkpoint inhibitor (ICI) and a tyrosine kinase inhibitor (TKI) is the standard first-line treatment for metastatic renal cell carcinoma (RCC). Oral TKIs enhance patient autonomy but require strict adherence and persistence. Methods: We analyzed adults with metastatic RCC at Chao Comprehensive Cancer Center, receiving at least 2 TKI prescriptions between April 29, 2019, and August 29, 2022, assessing adherence via Medication Possession Ratio (MPR) and Proportion of Days Covered (PDC). Results: A total of 66 individuals and 849 prescriptions were identified. The mean duration of TKI treatment was 237 days, with a median of 201 days. The mean persistence was 303 days, whereas the median was 233 days. Over 180 days, the median MPR was 83%, whereas the median PDC was 72%. The median variable PDC was 86%, while the median variable MPR was 105%. Asian patients experienced the longest average TKI therapy duration at 319 days, while Hispanic patients had the shortest at 223 days. Conclusions: We observed a significantly longer median duration of oral TKI therapy (201 days) than the reported national average (< 100 days). This analysis of real-world data reveals that lengthier treatment durations for TKI + ICI combinations are feasible.

The REnal cancer consortium for Focused Investigation of Novel biomarkers and Expression (REFINE) consortium represents an important initiative in integrating clinical data with molecular sequencing in patients with advanced renal cell carcinoma (RCC) treated with immunotherapy-based approaches. By leveraging real-world evidence and genomic analysis, this consortium aims to explore putative predictive biomarkers with the potential to inform personalized treatment strategies. Findings from the REFINE database may further contribute to our understanding of disease courses of immunotherapy-based approaches for various molecular subtypes of RCC, associations of race and ethnicity with RCC treatment and outcomes with representation of patient populations underrepresented in clinical trials, and optimizing treatment sequencing.

INTRODUCTION:Treatment of metastatic renal cell carcinoma (mRCC) has expanded with development of combination therapies containing tyrosine kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICI) agents or dual ICI agents. However, patient preferences may not necessarily be incorporated into management decisions. We aimed to understand patient preferences in the management of mRCC and compare it with oncologists' perspectives. METHODS:A single-arm, prospective study surveyed patients with mRCC utilizing a questionnaire containing descriptions of 5 treatment options in simple language. Patients rated their preference for each option on a scale from 1 (least preferred) to 10 (most preferred). The same questionnaire plus basic de-identified patients' characteristics were provided to 2 academic oncologists and 1 community oncologist. RESULTS:A total of 54 patients were surveyed. The most preferred patient treatment option was TKI with mean score of 7.9 while the least popular was early phase clinical trials (CTs) with a mean score of 5.9 (p < 0.01). Patient's employment status, speaking language, and denovo metastatic disease were the variables found to be associated with likelihood of picking a particular treatment option. Among oncologists, the most selected treatment options were enrollment in early and late phase CTs with mean scores of 7.61 and 7.52 respectively and single-agent TKI was least preferred with a mean score of 5.69 (p < 0.01). Age and performance status influenced oncologist therapy choices based on the multivariable analysis. CONCLUSIONS:This study unveils differences between patients and oncologists' treatment preferences for mRCC and underscores the importance of individualized discussion with each patient to evaluate his or her therapeutic objectives.

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

Ayurveda is commonly utilized in the treatment of medical ailments but has yet to gain traction in incorporation into allopathic medicine. Prostate cancer is the most common cancer among men and presents a significant public health burden across the globe. Despite advancements in the management of advanced prostate cancer including androgen deprivation therapy and novel hormonal therapies, men may eventually develop resistance to hormonal therapy. As such, there is an urgent need for novel therapeutic options in treating this malignancy. This review examines the pre-clinical evidence for Ayurveda medicinal plants such as Withania somnifera , Glycyrrhiza spp, Momordica spp, Boswellia , and Bacopa monnieri and their potential application in managing prostate cancer. Several in-vitro and pre-clinical studies suggest potentials for these plants or their derivatives in preventing or treating prostate cancers. Despite strong evidence of efficacy of these plants to potentially improve the outcome of prostate cancer, clinical trials are required to evaluate which plants may be most efficacious and to determine effective dosing strategies, as well as the use of ayurvedic plants as standalone therapies or in combination with conventional prostate cancer treatments.

BACKGROUND:Enfortumab vedotin combined with pembrolizumab (EV-P) has become the new standard first-line therapy for patients with advanced urothelial carcinoma (aUC), based on its superior efficacy over platinum-based chemotherapy. As this regimen is increasingly adopted in routine care, treatment decisions may often occur in sites without dedicated genitourinary oncology expertise. This global survey aimed to explore how physicians perceive clinical factors that may influence the safe and effective use of EV-P in daily practice. MATERIAL AND METHODS:A panel of international physicians with experience in treating patients with genitourinary cancers developed a 17-question survey addressing practice settings, experience in managing aUC, and clinical considerations relevant to the use of EV-P. The participants were recruited through a network-based convenience sampling method. The responses were descriptively analyzed. RESULTS:A total of 201 genitourinary physicians from 32 countries completed the questionnaire. The most frequently cited potential absolute contraindications were sensory or motor neuropathy grade ≥2 (64.2%), ECOG-PS ≥3 (59.2%), and non-urothelial component >50% of the tissue sample (59.2%). Other notable concerns included severe corneal/retinal abnormalities, HbA1c >11%, severe skin comorbidities, liver impairment grade ≥2, and dialysis dependence. CONCLUSIONS AND RELEVANCE:This survey provides practical insights into real-world physician perspectives on patient selection for EV-P. The findings highlight the need for guidance to support personalized risk assessment, facilitate early identification of patients who may require enhanced monitoring, and optimize safe integration of EV-P into clinical practice.

Urachal cancer, a rare malignancy, generally presents in the clinical setting with advanced stages of disease. Systemic treatment with chemotherapy is generally utilized in this setting. However, there remains a paucity of data on the effectiveness of immune checkpoint inhibitors or targeted therapies for urachal cancer. We analyzed the genomic profile of urachal cancer in order to identify potentially targetable mutations and evaluate the tumor microenvironment. 42 urachal samples were retrospectively analyzed. Our results showed that TP53, GNAS and KRAS mutations were common in urachal cancer with increased prevalence of TP53 mutation in urachal cohorts without MAPK-alterations. The tumor microenvironment demonstrated increased NK cells in MAPK-altered urachal cancer. Finally, we show that urachal cancer shares genomic and transcriptomic similarity with colorectal cancer compared to bladder cancer. This study provides new insights into the molecular profiles of urachal tumor samples and possibility of association with colorectal cancer that might guide future clinical trial design.

Penile cancer is a rare genitourinary malignancy which can be treated with surgery or radiation for localized disease, but often requires systemic treatment with chemotherapy for recurrent or metastatic disease. With the emergence of immune checkpoint inhibitors and targeted therapies for specific genomic aberrations in the treatment of over a dozen other cancers, recent studies have sought to identify therapies other than chemotherapy in treating this uncommon cancer. Several ongoing trials involving immune checkpoint inhibitors, tyrosine kinase inhibitors, and antibody drug conjugates are attempting to identify additional therapies.

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