OBJECTIVE:To characterise the prevalence and distribution of biopsy cores found to be higher grade on systematic biopsy compared to targeted biopsy in patients with prostate magnetic resonance imaging (MRI) lesions. PATIENTS AND METHODS:We retrospectively identified patients with a pre-biopsy MRI and a Prostate Imaging-Reporting and Data System score ≥3 lesion, who underwent combined systematic and targeted biopsy between 2021 and 2024. Transrectal and transperineal approaches with either software-based or cognitive fusion techniques were used. We compared the highest Gleason grade detected by systematic vs targeted biopsy for each patient. Clinically significant prostate cancer (csPCa) was defined as Gleason Grade Group ≥2. For those with higher-grade csPCa detected on systematic compared to targeted biopsy, we correlated the pathological location of the higher-grade systematic core to the corresponding MRI region(s) of interest (ROI). Multivariable logistic regression was used to determine factors associated with higher-grade csPCa found on systematic biopsy. RESULTS:Our final cohort comprised 481 patients. Detection of higher-grade csPCa on systematic biopsy outside of the MRI ROI occurred in 6.4% of all cases. Systematic biopsy detected higher-grade csPCa contralateral to the MRI ROI in only 1.5% of all cases. There were no identifiable factors on multivariable analysis associated with detection of higher-grade csPCa on systematic biopsy outside of the ROI. CONCLUSION:There exists a small percentage of patients with occult csPCa detected only on systematic biopsy outside of the MRI ROI, most of which is ipsilateral to the target. Systematic biopsy also increased detection of low-grade cancer overall. An approach of systematic biopsy ipsilateral to MRI lesions should increase csPCa detection while reducing overdiagnosis of low-grade disease.

ABSTRACT:Self-reported Black (B) individuals remain underrepresented in molecular studies of clear-cell renal cell carcinoma (ccRCC) relative to White (W) individuals. We performed whole-exome and transcriptome sequencing on paired tumor and normal samples from 59 matched B and W patients undergoing nephrectomy for localized ccRCC, comparing molecular differences by estimated genetic similarity to African (AFR) and European (EUR) 1000 Genomes groups. We validated our findings with a propensity-matched subset of The Cancer Genome Atlas, yielding a final cohort of 254 patients (79 AFR and 175 EUR) with similar baseline clinical variables. Significant differences emerged in VHL mutation frequency (AFR: 23.4%, EUR: 57.5%; FDR = 0.0029) and chromosome 3p deletions (AFR: 59.2%, EUR: 82.6%; FDR = 0.086). Transcriptomic analyses identified 34 genes associated with genetic similarity, and gene set enrichment revealed inflammatory (IFN-γ/IFN-α, allograft rejection), proliferative (E2F targets, G2–M checkpoint), and metabolic (bile acid, fatty acid, glycolysis, MTORC1, peroxisome) pathway enrichment in EUR. We also observed differences in ccRCC molecular subtype distribution, with “Proliferative” and “Angio/Stromal” subtypes being more common in AFR (P = 0.018). Importantly, differential subtype membership explained most group-level differences. These results link EUR and AFR genetic similarity to distinct ccRCC molecular subtypes, underscoring the importance of molecular classifiers in disease stratification and the need to include diverse populations in molecular studies to improve our understanding and treatment of ccRCC. SIGNIFICANCE:Our study shows that AFR genetic similarity correlates with distinct ccRCC molecular subtypes. Further research is needed to disentangle environmental and genetic influences. Identifying these differences underscores the critical importance of including racially and ethnically diverse populations in cancer research to ensure more equitable and sustainable outcomes worldwide for all patients.

ObjectiveTo evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS).Materials and MethodsWe queried the prospective, multi‐institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.5 cm/year was defined as a GR event. We used multivariable recurrent events and time‐to‐event Cox regression modelling to evaluate the association between tumour size and GR events (primary outcome) and tumour size and delayed intervention (DI; secondary outcome). We tested tumour size as a continuous variable and dichotomised tumour size by predefined (2‐cm) and calculated (2.9‐cm) cutoffs. We calculated the cutoff using maximally selected rank statistics and time to progression, defined according to the DISSRM registry.ResultsThe median (interquartile range) follow‐up of patients on AS was 40.1 (26.4–71.2) months, during which 128 patients (28%) had ≥1 GR event, and 80 (18%) underwent DI. Larger tumour size was an independent predictor for GR events and DI when tested as a continuous and a dichotomous variable in multivariable analyses (all P < 0.05). The association was strongest when accounting for the change in tumour size over time and when applying the 2.9‐cm cutoff. The study is limited by the mixed tumour pathology inert to SRMs.ConclusionLarger tumour size was independently associated with GR events and DI for patients with SRMs on AS. A 2.9‐cm cutoff may provide valuable information for patient counselling.

PURPOSE:Active surveillance (AS) is an alternative to primary intervention (PI) in the management of small renal masses (SRMs; clinical stage T1a). However, AS remains underutilized due to a lack of strong, prospective data. We herein report mature outcomes after a 12-year experience with the Delayed Intervention and Surveillance for Small Renal Masses Registry. MATERIALS AND METHODS:This was a multi-institutional prospective comparative study from 2009 to 2022 of patients with SRM who chose to undergo AS or PI. Primary outcomes were cancer-specific survival (CSS) and overall survival (OS). RESULTS:A total of 958 patients were enrolled; 581 chose AS, and 377 chose PI. Ultimately, 88 of 581 AS patients crossed over to delayed intervention. The median follow-up time for the registry was 4.15 years (IQR: 2.11-7.31) among patients who were still alive, with 406 patients followed for ≥ 5 years. Competing-risk CSS cumulative incidence function accounting for other causes of mortality for AS at 4 years and beyond is 0.19% (95% CI: 0.3%-1.4%), and for PI at 4 years and beyond is 0.68% (95% CI: 0.17%-2.7%). Gray's test for statistical differences between CSS CI curves of PI vs AS showed no statistical difference (P = .4). However, Kaplan-Meier analysis of OS showed it to be higher in patients undergoing PI compared with AS at 4 years (95% vs 88%), 6 years (92% vs 81%), 8 years (90% vs 66%), and 10 years (85% vs 64%); this difference was statistically significant; log-rank P < .001. CONCLUSIONS:In our study cohort, AS is not inferior to PI in patients with SRM suspicious for renal cell carcinoma. The difference in OS between AS and PI is most likely attributable to the increased risk of death from competing causes among AS patients. A priori definitions of progression, including growth rate, should be reconsidered.

Introduction The Delayed Intervention and Surveillance for Small Renal Masses Registry (DISSRM) is the world's largest ongoing prospective clinical trial comparing Active Surveillance(AS) versus Primary Intervention(PI) for Small Renal Masses (SRM). While previous results have shown that AS is safe with equivalent cancer-specific mortality to PI, overall survival(OS) remains significantly inferior for AS compared to PI. This difference is most likely due to the lack of randomization, with more elderly patients with comorbidities choosing AS over PI. Therefore, we conducted a propensity score matching analysis to mitigate the lack of randomization and investigate OS between evenly balanced study arms. Methods Using data from this multi-institutional prospective study comparing Active Surveillance (AS) and Primary Intervention(PI) for Small Renal Masses(SRM) from 2009 to 2022, we performed a Kaplan-Meier overall survival(OS) analysis. This analysis was conducted after a 1-to-1 exact propensity score matching, accounting for age, gender, and the Charlson Comorbidity Index (CCI). Subsequently, using the entire DISSRM cohort we conducted a competing-risks analysis to account for other causes of mortality, calculating the cumulative incidence function (CIF) of cancer-specific mortality, intervention, progression, and recurrence using the Fine and Gray method. Results We found 958 Patients enrolled in DISSRM with a median follow up time(MFT) of 4.1 years (IQR2.13–7.18), compromising of 377PI and 581AS patients. After the 1-to-1 exact propensity score matching a pseudo cohort of 754 patients (377PI and 377AS) was created. OS for PI compared to AS at 2-years (98.51%vs97.59%), 5-years(94.15%vs90.52%),7-years(91.84% vs 80.09%)log-rank(P=0.13), with Mortality hazard ratio for AS[HR=1.49(95%CI;0.89-2.49),P=0.13]. Competing-risk CSS CIF accounting for other causes of mortality for AS at 4-years and beyond is 0.19%(95%CI;0.3%–1.4%), and for PI at 4-years and beyond is 0.68%(95%CI;0.17%–2.7%). Gray's test(P=0.4). Progression CIF accounting for competing-risk of non-RCC mortality at 2-years=14.87%(95%CI:12.84%-17.20%), and 5-years=22.96%(95%CI:20.21%-26.03%) until it reaches 33.04%(95%CI:28.31%-38.32%) at 8-years and beyond. Recurrence CIF accounting for competing-risk of non-RCC death for PI at 4-years=1.3%(95%CI:0.47%-3.3%), 6-years=1.7%(95%CI:0.7%-4.0%), and 8-years=2.2%(95%CI:1.0%-4.8%). Meanwhile, the recurrence CIF for AS who received delayed intervention(DI) at 4-years and beyond is 4.4%(95% CI:1.1%-17.0%).Gray's test (P=0.511)[Figure1] Conclusions AS is safe and not inferior to Primary Intervention PI. In our study, we demonstrated that, after matching for age, gender, and CCI, there was no statistically significant difference in OS between AS and PI. This finding had not been demonstrated previously, primarily due to the insufficient sample size required for such an analysis. However, with 15-years of data from the ongoing trial, we were able to accumulate a sufficiently large dataset to perform this analysis, leading to this significant finding.

ccRCC driver mutations by AFR and EUR groups, race, and RCC clinical risk factors. A, OncoPrint of ccRCC driver mutations split by AFR and EUR groups. B, Frequency of VHL mutations in patients by HTN history, eGFR group, and self-reported race. Group-wise P values were calculated using Fisher’s exact test. Mut, mutant; SNV, single nucleotide variant; Wt, wild-type.

Active surveillance (AS) is an alternative to primary intervention (PI) in the management of small renal masses (SRMs; clinical stage T1a). However, AS remains underutilized due to a lack of strong, prospective data. We herein report mature outcomes after a twelve-year experience with the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry. Multi-institutional prospective comparative study from 2009 to 2022 of patients with SRM who chose to undergo AS or PI. Primary outcomes were cancer-specific survival (CSS) and overall survival (OS). A total of 958 patients were enrolled; 581 chose AS, and 377 chose PI. Ultimately, 88 of 581 AS patients crossed over to delayed intervention (DI). The median follow-up time for the registry was 4.15 years (IQR 2.11-7.31) among patients who were still alive, with 406 patients followed for ≥5 years. Competing-risk CSS cumulative incidence function (CIF) accounting for other causes of mortality for AS at 4 years and beyond is 0.19% (95% CI; 0.3% - 1.4%), and for PI at 4 years and beyond is 0.68% (95% CI; 0.17% - 2.7%). Gray's test for statistical differences between CSS CI curves of PI vs AS showed no statistical difference (P=0.4). However, Kaplan-Meier analysis of OS showed to be higher in patients undergoing PI compared to AS at 4 years (95% vs 88%), 6 years (92% vs 81%), 8 years (90% vs 66%), and 10 years (85% vs 64%), this difference was statistically significant; log-rank P<0.001. In our study cohort, AS is not inferior to PI in patients with SRM suspicious for renal cell carcinoma. Difference in OS between AS and PI is most likely attributable to the increased risk of death from competing causes among AS patients. A priori definitions of progression, including growth rate, should be re-considered.

This randomized clinical trial compares the effect of transperineal vs transrectal prostate biopsy on infection rates after biopsy.

You have accessJournal of UrologyJU Forum3 May 2024Advances in Molecular Imaging for Renal Tumors Zhuo Tony Su, Nirmish Singla, and Mohammad E. Allaf Zhuo Tony SuZhuo Tony Su Corresponding Author: Zhuo Tony Su, MD, Department of Urology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Marburg 134, Baltimore, MD 21287 ([email protected]) , Nirmish SinglaNirmish Singla , and Mohammad E. AllafMohammad E. Allaf View All Author Informationhttps://doi.org/10.1097/JU.0000000000003904AboutPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Contemporary evaluation of renal tumors remains reliant on conventional imaging modalities including CT, ultrasound, and MRI. CT and MRI provide high-resolution structural information of renal tumors, but these imaging modalities cannot characterize tumor biological processes and have a poor ability to differentiate among benign, indolent, and aggressive renal masses. This poor differentiation can lead to unnecessary treatment for benign masses and overtreatment for indolent tumors, while failure to timely intervene on aggressive renal cell carcinoma (RCC) risks metastatic progression. Furthermore, conventional CT does not offer sufficient sensitivity for detecting small foci of recurrent or metastatic RCC.1,2 CT and MRI also have limited utility for assessing RCC response to treatment, as these modalities can only characterize late treatment responses such as changes in tumor size and perfusion.1 Therefore, there is a clear need for improved diagnostic, staging, and surveillance imaging for patients with renal tumors. Recently, advances have been made in molecular imaging to address these limitations. Positron emission tomography (PET) and single-photon emission CT (SPECT) utilize radionuclide-labeled molecular tracers to target specific biological processes of renal tumors. When coadministered with conventional imaging, PET/CT, PET/MRI, and SPECT/CT combine the sensitivity and specificity of radiotracers with the high resolution of structural imaging.1 Because several common genetic mutations in RCCs are involved in various metabolic pathways and cause upregulation of tumor-specific cellular membrane proteins,1 radiotracers have been employed to target metabolites that preferentially accumulate in renal tumor cells and receptors that are selectively expressed on RCC cells (Table).1 Here we review several of these radiotracers as illustrative examples and highlight opportunities for further development. Table. Representative Radiotracers Targeting Membranous Receptors and Metabolic Pathways of Renal Tumors Radiotracer Receptor/metabolic pathway targeted Indications1,9 Tracers targeting membranous biomarkers cG250 (girentuximab) mAb ligand for CA-IX Diagnosis of primary RCC, detection of metastatic RCC, and assessment of response to TKI VM4-037 Small-molecule ligand for CA-IX Preclinical data suggest utility for detection of metastatic RCC XYIMSR-06 Small-molecule ligand for CA-IX Improved pharmacokinetics than other radiotracers targeting CA-IX; preclinical data suggest utility for diagnosis of primary RCC and detection of metastatic RCC; compatible with SPECT/CT 68Ga-PSMA-11 Small-molecule ligand for PSMA Detection of metastatic RCC 18F-PSMA-1007 Small-molecule ligand for PSMA Potential utility for diagnosis of primary RCC, detection of metastatic RCC, and assessment of response to TKI and ICI 18F-DCFPyL Small-molecule ligand for PSMA Detection of metastatic RCC 89Zr-bevacizumab mAb ligand for VEGFA Assessment of response to antiangiogenic treatment 89Zr-atezolizumab mAb ligand for PD-L1 Assessment of response to ICI Tracers targeting metabolic pathways 18F-FDG Glucose uptake and phosphorylation Surveillance for recurrent and metastatic RCC, and assessment of response to TKI and ICI 99mTc-sestamibi Uptake in cells with high mitochondrial content and low MDR pump expression Differentiation of renal oncocytomas and HOCTs from other renal masses 11C-acetate Lipid synthesis Diagnosis of primary RCC 11C-choline Cellular membrane synthesis Diagnosis of primary RCC 11C-methionine Amino acid metabolism RCC staging and prognosis prediction 18F-(2S,4R)-4-fluoroglutamine Amino acid metabolism Detection of glutamine-dependent RCC Abbreviations: CA-IX, carbonic anhydrase IX; FDG: fluoro-2-deoxy-d-glucose; HOCT, hybrid oncocytic/chromophobe tumor; ICI, immune checkpoint inhibitor; mAb, monoclonal antibody; MDR, multidrug resistance; PD-L1, programmed cell death ligand-1; PSMA, prostate-specific membrane antigen; RCC, renal cell carcinoma; SPECT/CT, single-photon emission CT/CT; TKI, tyrosine kinase inhibitor; VEGFA, vascular endothelial-derived growth factor A. METABOLIC RADIOTRACERS Among radiotracers targeting renal tumor metabolic pathways, 18F-fluorodeoxy-glucose (FDG) has been the most extensively studied. 18F-FDG is structurally similar to glucose and can be used to measure glucose uptake by tumor cells. 18F-FDG has limited utility for diagnosing primary RCC due to high renal uptake of the radiotracer. Instead, 18F-FDG may be suitable for detecting recurrent and metastatic RCC. In a retrospective study, 18F-FDG PET/CT demonstrated a sensitivity of 96% and specificity of 100% for RCC local recurrence after surgical resection, vs 100% and 98.6% for CT, and a sensitivity of 92.5% and specificity of 99.6% for distant metastases, compared to 93.3% and 94.0% for CT. While CT detected pulmonary metastases better, 18F-FDG PET/CT was more sensitive for nodal, bone, and soft tissue metastases.3 Moreover, 18F-FDG may be used to monitor RCC response to tyrosine kinase inhibitors and immune checkpoint inhibitors. For example, in a small prospective study of patients treated with nivolumab for metastatic RCC, elevated maximum standardized uptake value assessed by 18F-FDG PET/CT 1 month after treatment was an independent predictor of disease response.4 Larger, prospective, multi-institutional studies are needed to validate the clinical value of 18F-FDG PET/CT and other metabolic radiotracers before they can be adopted for routine use. MEMBRANE RECEPTOR LIGANDS An active area of research focuses on identifying and validating radiotracers targeting RCC-specific membranous receptors, with monoclonal antibody (mAb) ligands for carbonic anhydrase IX (CA-IX) among the most promising. CA-IX is a transmembrane protein that has very limited expression under normal physiological conditions but is highly expressed in over 95% of clear cell (cc) RCCs.1 The phase III multicenter REDECT trial demonstrated the utility of 124I-labeled chimeric G250 (cG250; girentuximab), a mAb targeting CA-IX, for diagnosing primary ccRCC. The study compared 124I-cG250 PET/CT and CT for detecting ccRCC in 195 patients undergoing surgery for resectable renal masses. 124I-cG250 PET/CT exhibited a sensitivity of 86.2% and specificity of 85.9% for detecting primary ccRCC lesions, superior to 75.5% and 46.8% for CT.5 Since 124I-labeled radiotracers tend to accumulate in the thyroid, 89Zr-labeled cG250 has been developed. Recently, a prospective, multicenter, phase 3 study (ZIRCON) evaluated the utility of 89Zr-cG250 for diagnosing primary ccRCC. In 284 patients, 89Zr-cG250 achieved a sensitivity of 85.5% and specificity of 87.0% for identifying primary ccRCC lesions, exceeding the study's predetermined sensitivity and specificity targets.6 Furthermore, 89Zr-cG250 has shown utility for detecting metastatic RCC. In a prospective study of 42 patients with metastatic ccRCC, 89Zr-cG250 PET/CT combined with CT detected 91% of metastatic lesions, significantly higher than 56% by CT alone and 84% by combined 18F-FDG PET/CT and CT.2 Currently, efforts are underway to develop and validate radiotracers of lower molecular weights than mAb ligands, in order to achieve better penetration to solid tumors, shorter circulation time, and therefore more rapid attainment of a high tumor-to-blood ratio convenient for real-world use. VM4-037 and XYIMSR-06 are 2 such small-molecule ligands for CA-IX. In a phase II study evaluating 18F-VM4-037 PET/CT in 11 patients, 18F-VM4-037 reached a tumor mean standardized uptake value of 2.55 at 1 hour after injection. However, high uptake of the tracer in the renal parenchyma limited visualization of primary renal lesions. In contrast, the tracer led to excellent visualization of CA-IX‒positive metastatic lesions, suggesting its potential utility for detecting metastatic RCC.764Cu-XYIMSR-06, a dual-motif small-molecule ligand for CA-IX, is particularly promising. In RCC xenograft models, 64Cu-XYIMSR-06 PET/CT demonstrated superior pharmacokinetics compared to existing radiotracers targeting CA-IX and most notably achieved an average tumor-to-kidney ratio of 7.1 at 24 hours post injection.8 Therefore, 64Cu-XYIMSR-06 may be the first small-molecule ligand for CA-IX appropriate for diagnosing primary RCC. Clinical evaluation of 64Cu-XYIMSR-06 is ongoing. SPECT/CT RADIOTRACERS All radiotracers discussed thus far have been applied in PET/CT imaging. Another opportunity in molecular imaging of renal tumors is to develop radiotracers for use with SPECT/CT. Currently, PET/CT remains expensive and not widely available, whereas SPECT/CT requires low costs and can be performed in most hospitals. A successful example of a SPECT/CT radiotracer employed for renal tumor imaging is 99Tc-sestamibi, a widely used radiotracer approved for imaging of multiple organs. Because of preferential 99Tc-sestamibi uptake in cells with high mitochondrial content and low multidrug resistance pump expression, characteristic of renal oncocytomas and hybrid oncocytic/chromophobe tumors, 99Tc-sestamibi SPECT/CT has been utilized to distinguish these 2 types of renal masses from malignant tumors. 99Tc-sestamibi SPECT/CT demonstrated a sensitivity of 87.5% and specificity of 95.2% for identifying renal oncocytomas and hybrid oncocytic/chromophobe tumors from other renal masses in prospective evaluation9 and has been adopted by centers across North America and Europe. Moreover, in health economic assessment, incorporation of 99Tc-sestamibi SPECT/CT to characterize indeterminate renal masses was noted to be cost-effective due to its low expense and avoidance of unnecessary treatment for benign renal masses.10 CONCLUSIONS Growing evidence suggests that molecular imaging can provide more sensitive and specific diagnosis of primary RCC, surveillance for recurrence, and detection of metastases than conventional imaging. Moreover, molecular imaging may be used to monitor RCC response to specific treatment and predict disease prognosis, thereby informing personalized treatment decisions for individual patients targeting their specific tumor biology. Small-molecule ligands for CA-IX, such as 64Cu-XYIMSR-06, which has exhibited improved pharmacokinetics than mAb radiotracers, have the potential to further enhance the diagnostic performance of molecular imaging. Additionally, development of radiotracers for use with SPECT/CT can reduce barriers to adoption of molecular imaging, thanks to the low cost and wide availability of SPECT/CT scans. Lastly, cost-effectiveness evaluations are needed to demonstrate the health economic value that molecular imaging may offer by improving clinical decision-making and treatment outcomes for patients with renal tumors. REFERENCES 1. . Molecular imaging of renal cell carcinoma in precision medicine. Mol Pharm.2022; 19(10):3457-3470. Crossref, Medline, Google Scholar 2. . Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2019; 46(9):1931-1939. Crossref, Medline, Google Scholar 3. . Diagnostic value of F-18 FDG PET/CT for local and distant disease relapse surveillance in surgically treated RCC patients: can it aid in establishing consensus follow up strategy?. Nucl Med Rev Cent East Eur. 2018; 21(2):85-91. Crossref, Medline, Google Scholar 4. . Early assessment with 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab. BMC Cancer. 2019; 19(1):298. Crossref, Medline, Google Scholar 5. . Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. J Clin Oncol.2013; 31(2):187-194. Crossref, Medline, Google Scholar 6. . Results from phase 3 study of 89Zr-DFO-girentuximab for PET/CT imaging of clear cell renal cell carcinoma (ZIRCON). J Clin Oncol.2023; 41(6 suppl l):LBA602. Crossref, Google Scholar 7. . PET/CT imaging of renal cell carcinoma with 18F-VM4-037: a phase II pilot study. Abdom Radiol.2016; 41(1):109-118. Crossref, Medline, Google Scholar 8. . [64Cu]XYIMSR-06: a dual-motif CAIX ligand for PET imaging of clear cell renal cell carcinoma. Oncotarget. 2016; 7(35):56471-56479. Crossref, Medline, Google Scholar 9. . Prospective evaluation of 99mTc-sestamibi SPECT/CT for the diagnosis of renal oncocytomas and hybrid oncocytic/chromophobe tumors. Eur Urol.2016; 69(3):413-416. Crossref, Medline, Google Scholar 10. . Cost-effectiveness analysis of 99mTc-sestamibi SPECT/CT to guide management of small renal masses. Eur Urol Focus. 2021; 7(4):827-834. Crossref, Medline, Google Scholar Funding/Support: None. Conflict of Interest Disclosures: The Authors have no conflicts of interest to disclose. Ethics Statement: __. Author Contributions: Conception and design: Su, Singla, Allaf. Drafting the manuscript: Su, Singla. Critical revision of the manuscript for scientific and factual content: Su, Singla, Allaf. Supervision: Su, Singla, Allaf. © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Zhuo Tony Su Corresponding Author: Zhuo Tony Su, MD, Department of Urology, Johns Hopkins University School of Medicine, 600 N Wolfe St, Marburg 134, Baltimore, MD 21287 ([email protected]) More articles by this author Nirmish Singla More articles by this author Mohammad E. Allaf More articles by this author Expand All Funding/Support: None. Conflict of Interest Disclosures: The Authors have no conflicts of interest to disclose. Ethics Statement: __. Author Contributions: Conception and design: Su, Singla, Allaf. Drafting the manuscript: Su, Singla. Critical revision of the manuscript for scientific and factual content: Su, Singla, Allaf. Supervision: Su, Singla, Allaf. Advertisement Advertisement PDF downloadLoading ...

Background The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. Methods In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. Findings Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53–69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5–42·4) in the nivolumab group and 30·1 months (21·9–41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74–1·21]; one-sided p=0·32). The most common treatment-related grade 3–4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3–5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. Interpretation Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. Funding US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted F-18-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with F-18-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm(3) (interquartile ratio [IQR], 1.16-3.36 cm(3)), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging/Surveillance III (PD58)1 May 2024PD58-05 ACTIVE SURVEILLANCE VERSUS PRIMARY INTERVENTION FOR CLINICAL T1A KIDNEY TUMORS: HOW DOES RENAL BIOPSIES MODULATE MANAGEMENT PLAN? CONTEMPORARY RESULTS THE FIFTEEN-YEAR DISSRM PROSPECTIVE COMPARATIVE STUDY Khalid Y. Alkhatib, Ian Mitchell Harmatz, Tina Wlajnitz, Nirmish Singla, Peter Chang, Andrew A. Wagner, Christian P. Pavlovich, James M. McKiernan, Thomas Guzzo, Mohamad E. Allaf, and Phillip M. Pierorazio Khalid Y. AlkhatibKhalid Y. Alkhatib , Ian Mitchell HarmatzIan Mitchell Harmatz , Tina WlajnitzTina Wlajnitz , Nirmish SinglaNirmish Singla , Peter ChangPeter Chang , Andrew A. WagnerAndrew A. Wagner , Christian P. PavlovichChristian P. Pavlovich , James M. McKiernanJames M. McKiernan , Thomas GuzzoThomas Guzzo , Mohamad E. AllafMohamad E. Allaf , and Phillip M. PierorazioPhillip M. Pierorazio View All Author Informationhttps://doi.org/10.1097/01.JU.0001008868.74763.2c.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) for small renal masses (SRMs; clinical stage T1a) remains underutilized due to a lack of strong, prospective data. We herein report contemporary outcomes results in era of increase renal biopsies utilization from the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry. METHODS: Since January, 2009, the DISSRM enrolled patients with a clinically localized, solid, enhancing renal mass ≤4.0 cm in diameter (cT1a). Patients can undergo delayed intervention (DI) or withdraw at any time. Protocol available at ClinicalTrials.gov (Identifier:NCT02346435). RESULTS: A total of 958 were enrolled, 377(39.35%) underwent PI and 581(60.65%) AS. The overall median follow-up time was 4.73 years (IQR: 2.13-7.18). Ultimately, 88 of 581 AS patients (15.15%) crossed over to DI after. The proportion of patients undergoing biopsies has increased from approximately 5% in the first 5 years to approximately 20%, 36 patients underwent biopsies. Of those 36, only 26 had an RCC (18 clear cell, 6 Papillary, and 2 unclassified type). CSS at 12-years was similar between PI and AS (99.3% vs 99.8%, respectively, log-rank p=0.43). OS was higher in patients undergoing PI compared to AS at 3-years (97.6% vs 92.9%), 6-years (92.8% vs 81.2%), 9-years (88.0% vs 63.7%), and 12-years (41.6% vs 57.9%) log-rank p<0.001. The median overall GR was 0.11 cm/year (IQR 0-0.33 cm/year), and 183 experienced a progression event. PFS was 84.3% at 3-years, 78.2% at 6-years, 77.3% at 9-years. Crossover rate is 15.16% (88/581) and was significantly different as the tumor size increases as fellow; size <2 cm; 10.28% (11/107), 2 to <3 cm; 16.25% (26/160); and ≥3 cm; 25.76% (51/198). RFS was not different between PI and DI (p=0.24). CONCLUSIONS: Given the absence of a randomized trial, DISSRM demonstrates the best available evidence of AS for SRM and confirms its safety a management strategy. Additionally, the results provide an opportunity to refine the approach to AS, including criteria for crossover to intervention. Tumor size at enrollment predicts DI and biological outcomes and should be considered the primary trigger for DI. Download PPTDownload PPT Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1215 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Khalid Y. Alkhatib More articles by this author Ian Mitchell Harmatz More articles by this author Tina Wlajnitz More articles by this author Nirmish Singla More articles by this author Peter Chang More articles by this author Andrew A. Wagner More articles by this author Christian P. Pavlovich More articles by this author James M. McKiernan More articles by this author Thomas Guzzo More articles by this author Mohamad E. Allaf More articles by this author Phillip M. Pierorazio More articles by this author Expand All Advertisement PDF downloadLoading ...

TPS5125 Background: B7-H3 is a member of the B7 superfamily, which includes PD-L1 (B7-H1) and PD-L2 (B7-DC). Enoblituzumab is a humanized Fc-optimized B7-H3–targeting antibody that induces antibody-dependent cellular cytotoxicity (ADCC). A recent investigator-initiated trial demonstrated that enoblituzumab therapy, used in the neoadjuvant prostate cancer setting, is feasible, safe, may enhance short-term clinical outcomes, and appears to stimulate intratumoral immune activation including CD8+ T cell infiltration and peripheral expansion of tumor-infiltrating T-cell clones that correlated with undetectable PSA at 1-year post-prostatectomy. To assess the impact of enoblituzumab on recurrence-free survival following prostatectomy, a phase 2, randomized, neoadjuvant clinical trial in high-risk localized prostate cancer patients has been started. We hypothesize that targeting B7-H3 with enoblituzumab will delay or prevent recurrence following prostatectomy compared to standard of care (SOC) . Methods: The HEAT trial is an investigator-initiated, multi-center, randomized, phase 2 study that is presently enrolling (NCT06014255). Eligible patients will undergo a pre-treatment prostate biopsy and conventional imaging (CT and bone scan) as well as PSMA-PET. Patients who have clinical stage cT1c-T3b, cN0 cM0 disease by conventional imaging (N1 by PSMA allowed with up to 3 LNs each ≤1 cm) will be eligible as long as concurrent hormonal or radiation therapy is not given. Prostate biopsy, within 3 months of enrollment, needs to show at least 3 positive cores containing at least 1 core with at least 50% disease involvement with Gleason ≥4+3=7 disease (with at least 1 additional high-risk feature such as PSA>20 ng/ml or cT3) or a Gleason sum ≥8. Patients will receive enoblituzumab at a dose of 15mg/kg IV biweekly for 6 doses (12 weeks) on the treatment arm, followed by prostatectomy, or will be scheduled for prostatectomy directly within 4-8 weeks on the SOC arm. 219 patients will be randomized (2:1) to treatment versus SOC. Pre-treatment, on-treatment, and post-treatment biomarkers of response and resistance will be collected. Patients will be followed according to standard institutional practices, but will require PSA evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-5. In both arms, salvage or adjuvant therapy will occur after biochemical or radiographic progression. The primary endpoint is recurrence-free survival (RFS) defined as any metastasis events, local pelvic visceral or lymph node recurrence, detectable prostate-specific antigen (PSA), or start of subsequent local or systemic therapy (including salvage or adjuvant therapy), or death for any cause, whichever occurs first. Secondary endpoints include additional clinical and immunologic correlates. Clinical trial information: NCT06014255 .

Introduction Active surveillance (AS) is an alternative to primary intervention (PI) in the management of small renal masses (SRMs; clinical stage T1a). However, AS remains underutilized due to a lack of strong, prospective data. One of the barriers to the widespread implementation of AS is the lack of prospectively conducted comparative studies with long-term follow-up. While a randomized trial is not feasible due to the reliance of AS on patient selection, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry prospectively enrolls patients with cT1a SRM who elect either AS or primary intervention (PI) through shared-decision making. We herein report mature outcomes results from the world's largest SRM prospective registry. Methods Since January, 2009, the DISSRM Registry has prospectively enrolled patients with SRMs who choose to undergo PI or AS. The protocol is available at ClinicalTrials.gov (Identifier:NCT02346435). In brief, enrollees are ≥18 years with a clinically localized, solid, enhancing renal mass ≤4.0 cm in diameter (cT1a) on axial imaging. For those on AS, intervention is recommended upon evidence of tumor progression, which is defined as: (1) growth rate (GR) >0.5 cm/year, (2) maximum tumor diameter (MTD) >4.0 cm, or (3) the development of symptoms or (4) metastatic disease. Patients can choose to undergo delayed intervention (DI) or withdraw at any time. Progression-free survival (PFS) was defined as a priori at the inception of the registry based on previous retrospective data and is calculated by evidence of progression (criteria 1-4) or (5) crossover to intervention. Recurrence-free survival (RFS) was defined as freedom from any tumor recurrence (criteria 1-5) or (6) death. Results 958 participants enrolled, 377(39.35%) PI and 581(60.65%) AS. Median follow-up was 4.73 years (interquartile range (IQR) 2.13-7.18). Of AS patients, 88 of 581(15.15%) crossed over to DI. PI and AS had similar 12-year cancer-specific survival (CSS) (99.3% vs 99.8%, respectively, log-rank P=0.43). Overall survival was higher in PI patients compared to AS at 3- (97.6% vs 92.9%), 6- (92.8% vs 81.2%), 9- (88.0% vs 63.7%), and 12-years (41.6% vs 57.9%) log-rank P<0.001. Median overall GR was 0.11 cm/year (IQR 0-0.33 cm/year), and 183 experienced progression events. PFS was 84.3% at 3-years, 78.2% at 6-years, 77.3% at 9-years. Crossover rate is 15.16% (88/581), differing significantly with tumor size: <2 cm;10.28% (11/107), 2 to <3 cm;16.25% (26/160); and ≥3 cm; 25.76% (51/198). RFS was not different between PI and DI (P=0.24). Conclusions With fourteen years of experience, the present analysis provides the world's largest prospective comparison of PI to AS with or without DI. Given the absence of a randomized trial, DISSRM demonstrates the best available evidence on appropriateness of AS for cT1a renal masses and confirms suggestions of earlier reports that AS is non-inferior to PI as an initial management strategy. Additionally, the study provides an opportunity to refine the historical approach to AS, including criteria for crossover to intervention. A priori definitions of progression, including GR, do not foretell biological outcomes including adverse pathology, recurrence, or CSS, but prompt increased rates of DI with increasing GR. Increasing tumor size at enrollment and throughout AS predicts DI and biological outcomes including adverse pathology, recurrence, and metastatic progression, and should be considered the primary trigger for DI in patients with an SRM.

Indeterminate renal masses are increasingly incidentally found on cross-sectional imaging. 99mTc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) scans can be used to identify oncocytomas and oncocytic renal neoplasms, including a subset of chromophobe renal cell carcinomas (chRCCs), which are viewed as false-positive. Patients imaged with renal sestamibi scans between 2014 and 2023 were reviewed. Those patients with solitary tumors that were originally classified as chRCC were included in the analysis. Imaging with SPECT/CT from the liver dome down had been carried out 75 min after the administration of 925 MBq of 99mTc-sestamibi. All available H E and immunostained slides were re-reviewed and classified according to WHO 2022 criteria. Confirmatory immunohistochemical stains were performed in tumors considered morphologically suspicious for non-chRCC entities. A total of 18 patients with solitary tumors were included in the final analysis. 13/18 (72.2