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Yale Urology Research [Q1: January-March 2024]

April 24, 2024

Primary Faculty / Residents / Research Associates

Sterling J, Simhan J, Flynn BJ, Rusilko P, França WA, Ramirez EA, Angulo JC, Martins FE, Patel HV, Higgins M, Swerdloff D, Nikolavsky D. Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis. J Urol. 2024 Apr;211(4):596-604. doi: 10.1097/JU.0000000000003848. Epub 2024 Jan 26. PMID: 38275201.

D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

Honig SC. Editorial: Ex-vivo Onco-Testis Microdissection. Fertil Steril. 2024 Mar 28:S0015-0282(24)00198-5. doi: 10.1016/j.fertnstert.2024.03.023. Epub ahead of print. PMID: 38554764.

Watching this video will help the surgeon plan an ex vivo microdissection. This will include extraction of seminiferous tubules and examination intraoperatively for the presence of sperm.

Gross M, Haider SP, Ze'evi T, Huber S, Arora S, Kucukkaya AS, Iseke S, Gebauer B, Fleckenstein F, Dewey M, Jaffe A, Strazzabosco M, Chapiro J, Onofrey JA. Automated graded prognostic assessment for patients with hepatocellular carcinoma using machine learning. Eur Radiol. 2024 Mar 27. doi: 10.1007/s00330-024-10624-8. Epub ahead of print. PMID: 38536464.

Machine learning reliably, rapidly, and reproducibly predicts mortality risk in patients with hepatocellular carcinoma from data routinely acquired in clinical practice.

Monaghan TF, Fang A, Ksido LR, Hachicho C, Muneeb M, Rahman SN, Bou Kheir G, Lazar JM, Everaert K, Wein AJ, Weiss JP. Prevalence of Sleep CALM nocturia factors in a male veteran population. Neurourol Urodyn. 2024 Mar 21. doi: 10.1002/nau.25410. Epub ahead of print. PMID: 38511613.

The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

Lokeshwar S; [Choksi A; Brito J; Renzulli J; Sprenkle P]. A0305 pathologic gleason upgrading following high-resolution micro-ultrasound, conventional ultrasound and MRI fusion biopsy techniques: A comparative study. European urology. 03/2024;85:S1101. doi: 10.1016/S0302-2838(24)00884-4.

Conclusions: Both micro ultrasound and MRI-ultrasound fusion were associated with improved Gleason grade group concordance between biopsy and RP pathology compared with systematic biopsy. We did not identify significant differences between micro ultrasound and MRIfusion approaches which may suggest similar benefits in terms of disease sampling.

Sundaresan V; [Jalfon M; Kim IY]. INTER-RATER RELIABILITY AND DIAGNOSTIC ACCURACY OF PI-RADS SCORING BETWEEN ACADEMIC AND COMMUNITY CARE NETWORKS: HOW WIDE IS THE GAP. Urologic oncology. 03/2024;42:S101. doi: 10.1016/j.urolonc.2024.01.281.

The PI-RADS scoring system is widely employed for the detection and evaluation of PCa using mpMRI. Our results suggest that diagnostic accuracy of mpMRI for detecting csPCa is not significantly different between academic and community practices. However, significantly poor reliability of mpMRI was observed between cohorts, suggesting the risk of introducing practice variation for prostate cancer management in the community.

Sundaresan VM; [Webb L; Rabil M; Sprenkle P; Kim IY; Leapman M]. RISKS OF GRADE RECLASSIFICATION AMONG PATIENTS WITH GLEASON GRADE GROUP 1 PROSTATE CANCER AND PI-RADS 5 FINDINGS ON PROSTATE MRI. Urologic oncology. 03/2024;42:S79. doi: 10.1016/j.urolonc.2024.01.222.

The majority of patients diagnosed with GG1 prostate cancer in the setting of a PI-RADS 5 lesion will be found to have GG2 or higher disease in the short term during active surveillance or during treatment, suggesting substantial initial misclassification. These findings reinforce the need for confirmatory testing in these patients due to risks of disease under-sampling.

Zeevi T, Leapman MS, Sprenkle PC, Venkataraman R, Staib LH, Onofrey JA. Reliable Prostate Cancer Risk Mapping From MRI Using Targeted and Systematic Core Needle Biopsy Histopathology. IEEE Trans Biomed Eng. 2024 Mar;71(3):1084-1091. doi: 10.1109/TBME.2023.3326799. Epub 2024 Feb 26. PMID: 37874731; PMCID: PMC10901528.

This study proposes a personalized whole-gland prostate cancer risk mapping post-biopsy to allow clinicians to better stage and personalize focal therapy treatment plans.

Boroda JU, De Leon B, Khosla L, Chobufo MD, Rahman SN, Lazar JM, Weiss JP, Monaghan TF. Application of the Sleep C.A.L.M. Tool for Assessing Nocturia in a Large Nationally Representative Cohort. Int Neurourol J. 2024 Feb;28(Suppl 1):55-61. doi: 10.5213/inj.2346258.129. Epub 2024 Feb 29. PMID: 38461857; PMCID: PMC10932577.

Sleep C.A.L.M. burden is associated with increased odds of nocturia in a dose-dependent fashion, and potentially a relevant means by which to organize the underlying etiologies for nocturia among community-dwelling adults.

Reddy S; [Honig S; Rotker K]. (376) high capability of ChatGPT to answer common patient questions on vasectomy reviewed by sexual medicine specialists. Journal of sexual medicine. 02/2024;21(supplement_1). doi: 10.1093/jsxmed/qdae001.361.

Our results demonstrate the capability of using ChatGPT as a potentially reliable source of information for patients desiring vasectomy counseling. Given the high clinical volume faced by many vasectomy providers, ChatGPT could possibly improve patient satisfaction and reduce provider burden.

Reddy S; [Honig S; Rotker K]. (121) utilizing ChatGPT for urology trainee simulation of Peyronie’s disease counseling. Journal of sexual medicine. 02/2024;21(supplement_1). doi: 10.1093/jsxmed/qdae001.115.

Our findings demonstrate that ChatGPT has potential to be a successful tool for urology resident and medical student education on Peyronie’s disease counseling. However, there was disagreement in trainee ratings between ChatGPT and the sexual medicine specialist.

Heckscher D; [Honig S; Rotker K]. (013) how do sexual medicine specialists handle patient counseling and penile rehabilitation in patients undergoing robotic assisted radical prostatectomy (ralp): Trends in pre op and post operative management. Journal of sexual medicine. 02/2024;21(supplement_1). doi: 10.1093/jsxmed/qdae001.011.

Despite new guidelines for evaluation and treatment of patients undergoing RALP, there appears to be diverse counseling, recommendations and treatment both preoperatively and postoperatively. Evidence based and expert opinion guidelines may alter pre operative counseling and treatment in the future.

Leapman M; [Rabil M; Sprenkle P; Kim IY]. Temporal and regional patterns of prostate cancer positron emission tomography imaging among commercial insurance beneficiaries in the united states. Journal of clinical oncology. 02/2024;42(4_suppl):34-34. doi: 10.1200/JCO.2024.42.4_suppl.34.

In this study from a large commercial US health insurer, PSMA-PET was rapidly incorporated into clinical practice and is now the dominant prostate cancer radiotracer. However, the initial uptake of PSMA-PET may be accompanied by disparity, as our data suggests less use in areas with lower income and education measures.

Kim IE; [Sprenkle PC; Leapman MS; Brito JM; Renzulli J; Kim IY]. Association between pelvic lymph node dissection and survival among patients with prostate cancer treated with radical prostatectomy. Prostate international. 02/2024. doi: 10.1016/j.prnil.2024.01.002.

Although the clinical benefits of pelvic lymph node dissection (PLND) at the time of radical prostatectomy for prostate cancer remain uncertain, major guidelines recommend PLND based on risk profile. Thus, the objective of this study was to examine the association between PLND and survival among patients undergoing RP stratified by Gleason grade group (GG) with the aim of allowing patients and physicians to make more informed care decisions about the potential risks and benefits of PLND.

Gross M, Huber S, Arora S, Ze'evi T, Haider SP, Kucukkaya AS, Iseke S, Kuhn TN, Gebauer B, Michallek F, Dewey M, Vilgrain V, Sartoris R, Ronot M, Jaffe A, Strazzabosco M, Chapiro J, Onofrey JA. Automated MRI liver segmentation for anatomical segmentation, liver volumetry, and the extraction of radiomics. Eur Radiol. 2024 Jan 13. doi: 10.1007/s00330-023-10495-5. Epub ahead of print. PMID: 38217704.

Liver volumetry, anatomic localization, and extraction of quantitative imaging biomarkers require accurate segmentation, but manual segmentation is time-consuming. A deep convolutional neural network demonstrates fast and accurate segmentation performance on T1-weighted portal venous MRI.

Chua KJ, Kronstedt S, Kaldany A, Srivastava A, Doppalapudi SK, Liu H, Tarhini AA, Gatti-Mays M, Gaughan E, Hu-Lieskovan S, Aljumaily R, Nepple K, Schneider B, Sterling J, Singer EA. Comparing the rate of immunotherapy treatment change due to toxicity by sex. Cancer Rep (Hoboken). 2024 Feb;7(2):e1932. doi: 10.1002/cnr2.1932. Epub 2024 Jan 8. PMID: 38189893; PMCID: PMC10849926.

Females received a shorter course of IO than males. However, there was no significant difference in the treatment discontinuation rate due to toxicity between males and females receiving IO. Toxicity-related treatment change was associated with COPD.

Panja S, Truica MI, Yu CY, Saggurthi V, Craige MW, Whitehead K, Tuiche MV, Al-Saadi A, Vyas R, Ganesan S, Gohel S, Coffman F, Parrott JS, Quan S, Jha S, Kim I, Schaeffer E, Kothari V, Abdulkadir SA, Mitrofanova A. Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC. Nat Commun. 2024 Jan 8;15(1):352. doi: 10.1038/s41467-024-44686-5. PMID: 38191557; PMCID: PMC10774320.

Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs.

Pak DH, Liu M, Kim T, Liang L, Caballero A, Onofrey J, Ahn SS, Xu Y, McKay R, Sun W, Gleason R, Duncan JS. Patient-Specific Heart Geometry Modeling for Solid Biomechanics Using Deep Learning. IEEE Trans Med Imaging. 2024 Jan;43(1):203-215. doi: 10.1109/TMI.2023.3294128. Epub 2024 Jan 2. PMID: 37432807; PMCID: PMC10764002.

The main novelty in our method is the use of minimally sufficient surface mesh labels for precise spatial accuracy and the simultaneous optimization of isotropic and anisotropic deformation energies for volumetric mesh quality.

Justice AC, Tate JP, Howland F, Gaziano JM, Kelley MJ, McMahon B, Haiman C, Wadia R, Madduri R, Danciu I, Leppert JT, Leapman MS, Thurtle D, Gnanapragasam VJ. Adaption and National Validation of a Tool for Predicting Mortality from Other Causes Among Men with Nonmetastatic Prostate Cancer. Eur Urol Oncol. 2024 Jan 2:S2588-9311(23)00289-4. doi: 10.1016/j.euo.2023.11.023. Epub ahead of print. PMID: 38171965.

Veterans Aging Cohort Study Charlson Comorbidity Index is ready for application within the Veterans Health Administration. Electronic health record-assisted calculation is feasible, improves accuracy over age and Charlson Comorbidity Index alone, and might help mitigate inaccuracy and bias in provider estimation of the risk of non-prostate cancer mortality.

Allam O, Dinis J, Almeida MN, Junn A, Mozaffari MA, Shah R, Chong L, Olawoyin O, Mehta S, Park KE, Avraham T, Alperovich M. Smooth versus Textured Tissue Expanders: Comparison of Outcomes and Complications in 536 Implants. Arch Plast Surg. 2024 Feb 7;51(1):42-51. doi: 10.1055/s-0043-1775592. PMID: 38425846; PMCID: PMC10901592.

As many surgeons have transitioned away from textured implants, our study shows that smooth TEs have similar outcomes to the textured alternatives.

Cunningham SD, Lindberg S, Joinson C, Shoham D, Chu H, Newman D, Epperson N, Brubaker L, Low LK, Camenga DR, LaCoursiere DY, Meister M, Kenton K, Sutcliffe S, Markland AD, Gahagan S, Coyne-Beasley T, Berry A; Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium*; [Rickey LM]. Association Between Maternal Depression and Lower Urinary Tract Symptoms in Their Primary School-Age Daughters: A Birth Cohort Study. J Wound Ostomy Continence Nurs. 2024 Jan-Feb 01;51(1):53-60. doi: 10.1097/WON.0000000000001039. PMID: 38215298; PMCID: PMC10794027.

Exposure to maternal depression in the prenatal and postpartum periods was associated with an increased likelihood of LUTS in daughters. This association may be an important opportunity for childhood LUTS prevention. Prevention strategies should reflect an understanding of potential biological and environmental mechanisms through which maternal depression may influence childhood LUTS.

Secondary Faculty

Meli K.; [Braun DA] Abstract 5673: Transposable element expression patterns in epigenetic mutational subtypes of clear cell renal cell carcinoma. Cancer research (Chicago, Ill.). 03/2024;84(6_supplement):5673-5673. doi: 10.1158/1538-7445.AM2024-5673.

Clear cell renal cell carcinoma (ccRCC) is characterized by mutations in epigenetic modulators and by aberrant transposable element (TE) expression, each of which have been separately associated with immunotherapy (IO) benefit in specific clinical contexts. However, the relationship between mutations in epigenetic regulators and TE expression, and the potential effect of both somatic mutations and TE expression on clinical outcomes, has not been fully investigated.

Grant MJ; [Petrylak DP]. Efficacy of antibody drug conjugates alone and in combination with other agents in metastatic urothelial carcinoma: A scoping review. Bladder Cancer. 03/2024;10(1):9-23. doi: 10.3233/BLC-230070.

In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement.

Han S, Camp SY, Chu H, Collins R, Gillani R, Park J, Bakouny Z, Ricker CA, Reardon B, Moore N, Kofman E, Labaki C, Braun D, Choueiri TK, AlDubayan SH, Van Allen EM. Integrative Analysis of Germline Rare Variants in Clear and Non-Clear Cell Renal Cell Carcinoma. medRxiv [Preprint]. 2023 Jan 19:2023.01.18.23284664. doi: 10.1101/2023.01.18.23284664. Update in: Eur Urol Open Sci. 2024 Mar 08;62:107-122. PMID: 36712083; PMCID: PMC9882438.

RCC encompasses a set of histologically distinct cancers with a high estimated genetic heritability, of which only a portion is currently explained. Previous rare germline variant studies in RCC have usually pooled clear and non-clear cell RCCs and have not adequately accounted for population stratification that may significantly impact the interpretation and discovery of certain candidate risk genes.

Saad E; [Braun D]. Multi-omic characterization of acquired resistance to immune checkpoint inhibitors in patients with metastatic renal cell carcinoma. Journal of clinical oncology. 02/2024;42(4_suppl):459-459. doi: 10.1200/JCO.2024.42.4_suppl.459.

While immune checkpoint inhibitors (ICI) have improved outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC), acquired resistance (ARX) is commonly encountered. We aimed to characterize the genomic and transcriptomic correlates underlying ARX in ICI-treated mRCC patients.

Saliby RM; [Braun D]. Evaluating intermediate endpoints (IE) for overall survival (OS) in metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI): An IMDC study. Journal of clinical oncology. 02/2024;42(4_suppl):400-400. doi: 10.1200/JCO.2024.42.4_suppl.400.

In Ph3 trials, assessment for primary endpoint of OS necessitates extended follow-up (f/u) periods, larger pool of events, and higher associated costs. We sought to determine if shorter IEs like Time to Treatment Failure (TTF) and Time to Next Therapy (TTNT) are associated with OS in patients (pts) receiving ICI-based trt.

Serzan MT; [Braun DA]. Advanced renal cell cancer combination immunotherapy clinical trial (ARCITECT; HCRN GU 22-587). Journal of clinical oncology. 02/2024;42(4_suppl):TPS492-TPS492. doi: 10.1200/JCO.2024.42.4_suppl.TPS492.

First-line treatment for patients with metastatic clear cell renal cell carcinoma (mccRCC) often includes an anti-PD1 inhibitor in combination with either an anti-CTLA inhibitor (IO/IO) or a VEGF receptor tyrosine kinase inhibitor (TKI) (IO/TKI). Although some patients treated with nivolumab/ipilimumab (Nivo/Ipi) (IO/IO) experience durable responses leading to treatment free intervals, over two-thirds experience disease progression.

El Ahmar N; [Braun DA]. Tumor-infiltrating CD163-positive macrophages and clinical outcomes to first-line nivolumab therapy in patients with advanced clear cell renal cell carcinoma (ccRCC) enrolled in the HCRN GU16-260 trial. Journal of clinical oncology. 02/2024;42(4_suppl):448-448. doi: 10.1200/JCO.2024.42.4_suppl.448.

Levels of tumor-infiltrating CD163-positive macrophages are associated with improved clinical outcomes to first-line nivolumab in pts with advanced ccRCC up to a density threshold, above which an association with poor outcomes is noted. Further investigations into the role of tumor-infiltrating myeloid cells in predicting outcomes to anti-PD-1-based therapies are ongoing. Clinical trial information: NCT05403541.

Aragon-Ching JB; [Petrylak DP]. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN bladder 100 trial in patients (pts) with high body mass index (BMI). Journal of clinical oncology. 02/2024;42(4_suppl):600-600. doi: 10.1200/JCO.2024.42.4_suppl.600.

This exploratory analysis shows the long-term efficacy and tolerability of avelumab 1L maintenance in pts with high BMI in JAVELIN Bladder 100, with no new safety concerns identified. These results further support the use of avelumab 1L maintenance as standard of care in pts with aUC who are progression free after 1L platinum-based chemotherapy, including pts with high BMI. Clinical trial information: NCT02603432.

Labaki C; [Braun D]. Cellular and molecular determinants of limited anti-tumor immunity in chromophobe renal carcinoma (ChRCC). Journal of clinical oncology. 02/2024;42(4_suppl):476-476. doi: 10.1200/JCO.2024.42.4_suppl.476.

ChRCC is a rare form of kidney cancer with a poor prognosis in the metastatic setting, in part due to very limited responses to immune checkpoint inhibitors (ICIs), as compared to clear cell RCC (ccRCC). The mechanisms underlying the poor response of ChRCC to ICIs remain largely uncharacterized. We therefore investigated at the single-cell resolution the cellular and molecular determinants of anti-tumor immunity in ChRCC.

Cheng HH; [Petrylak DP]. SWOG S2210: A phase II study of neoadjuvant carboplatin for localized, high-risk prostate cancer with germline BRCA1/2 mutations. Journal of clinical oncology. 02/2024;42(4_suppl):TPS354-TPS354. doi: 10.1200/JCO.2024.42.4_suppl.TPS354.

Carriers of germline pathogenic variants or mutations in BRCA2 and BRCA1 (referred to here as gBRCA1/2m) are enriched in metastatic prostate cancer (PrCa), and now have FDA-approved options for PARP inhibitors in late-stage disease. The NCCN guidelines recommends germline genetic testing for PrCa patients with metastatic, node positive and high risk localized prostate cancer. Prior studies have shown that gBRCA1/2m carriers with PrCa are more likely to have high-risk disease (6,7) and to develop lethal disease even after curative intent treatment (8,9). In other gBRCA1/2m-related cancers (breast, ovarian and pancreas), platinum-based regimens are part of neoadjuvant and front-line metastatic therapy options. Carboplatin is a well-tolerated, widely available and inexpensive DNA-damaging alkylating agent that is familiar to oncologists. The study hypothesis is that 4 cycles of neoadjuvant carboplatin, followed by radical prostatectomy for patients with localized high/very high risk PrCa and gBRCA1/2m will result in a meaningful pathologic complete response (pCR) rate.

Semaan K; [Braun D]. Detection of sarcomatoid renal cell carcinoma using plasma cell-free DNA methylation. Journal of clinical oncology. 02/2024;42(4_suppl):449-449. doi: 10.1200/JCO.2024.42.4_suppl.449.

Sarcomatoid differentiation (SD) in renal cell carcinoma (RCC) is associated with poor survival and heightened response to immune checkpoint blockade. Detection of SD can be challenging due to spatial heterogeneity and sampling error. Herein, we introduce a novel tissue–informed epigenomic approach to noninvasively identify sarcomatoid differentiation in patients with RCC from cell-free DNA (cfDNA) using <1mL of plasma.

Grivas P, Pouessel D, Park CH, Barthelemy P, Bupathi M, Petrylak DP, Agarwal N, Gupta S, Fléchon A, Ramamurthy C, Davis NB, Recio-Boiles A, Sternberg CN, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa ST, Loriot Y. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3. J Clin Oncol. 2024 Apr 20;42(12):1415-1425. doi: 10.1200/JCO.22.02835. Epub 2024 Jan 23. PMID: 38261969.

SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.

Loriot Y, Petrylak DP, Rezazadeh Kalebasty A, Fléchon A, Jain RK, Gupta S, Bupathi M, Beuzeboc P, Palmbos P, Balar AV, Kyriakopoulos CE, Pouessel D, Sternberg CN, Tonelli J, Sierecki M, Zhou H, Grivas P, Barthélémy P, Tagawa ST. TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes. Ann Oncol. 2024 Apr;35(4):392-401. doi: 10.1016/j.annonc.2024.01.002. Epub 2024 Jan 18. PMID: 38244927.

Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear.

Wang Y, Cho JW, Kastrunes G, Buck A, Razimbaud C, Culhane AC, Sun J, Braun DA, Choueiri TK, Wu CJ, Jones K, Nguyen QD, Zhu Z, Wei K, Zhu Q, Signoretti S, Freeman GJ, Hemberg M, Marasco WA. Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model. iScience. 2024 Jan 15;27(2):108879. doi: 10.1016/j.isci.2024.108879. PMID: 38327771; PMCID: PMC10847687.

Analysis of the TME revealed that G36-PDL1 CAR-T cells restored active antitumor immunity by promoting tumor-killing cytotoxicity, reducing immunosuppressive cell components such as M2 macrophages and exhausted CD8+ T cells, and enhancing T follicular helper (Tfh)-B cell crosstalk.

Milowsky MI, O'Donnell PH, Hoimes CJ, Petrylak DP, Flaig TW, Moon HH, Friedlander TW, Mar N, McKay RR, Srinivas S, Gravis G, Ramamurthy C, Bupathi M, Bracarda S, Wright P, Hepp Z, Carret AS, Yu Y, Dillon R, Kataria R, Beaumont JL, Purnajo I, Rosenberg JE. Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab. J Clin Oncol. 2024 Apr 20;42(12):1403-1414. doi: 10.1200/JCO.23.01547. Epub 2024 Jan 12. PMID: 38215355.

Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K.

Denize T, Jegede OA, Matar S, El Ahmar N, West DJ, Walton E, Bagheri AS, Savla V, Nabil Laimon Y, Gupta S, Vemula SV, Braun DA, Burke KP, Catalano PJ, Freeman GJ, Motzer RJ, Atkins MB, McDermott DF, Sharpe AH, Choueiri TK, Signoretti S. PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti-PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients. Clin Cancer Res. 2024 Feb 16;30(4):803-813. doi: 10.1158/1078-0432.CCR-23-2274. PMID: 38060202; PMCID: PMC10922154.

PD-1 expression on Tregs is associated with resistance to PD-1 blockade in mccRCC, suggesting that targeting Tregs may synergize with PD-1 inhibition. A model that integrates PD-1 expression on Tregs and CD8+TIM-3-LAG-3- cells has higher predictive value.

Saliby RM, Saad E, Kashima S, Schoenfeld DA, Braun DA. Update on Biomarkers in Renal Cell Carcinoma. Am Soc Clin Oncol Educ Book. 2024 Jan;44(2):e430734. doi: 10.1200/EDBK_430734. PMID: 38207251.

Current research is exploring host factors through in-depth characterization of the immune system. Additionally, innovative technological approaches are being developed to overcome challenges presented by existing techniques, such as tumor heterogeneity. Promising avenues in biomarker discovery include the study of the microbiome, radiomics, and spatial transcriptomics.

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