PHASE II TRIAL OF NEOADJUVANT SITRAVATINIB PLUS NIVOLUMAB IN PATIENTS UNDERGOING NEPHRECTOMY FOR LOCALLY ADVANCED CLEAR CELL RENAL CELL CARCINOMA
Sitravatinib inhibits angiogenesis and mitigates immunosuppressive effects in the tumor microenvironment (TME), thereby improving the efficacy of immune checkpoint inhibitors by producing a less immunosuppressive TME.[1] In this single-arm, interventional, phase 2 study, neoadjuvant sitravatinib in combination with nivolumab was administered to 17 patients with T2b–T3a clear cell renal cell carcinoma.[2] The median follow-up was 26 months. The objective response rate was 11.8% with two radiologic partial responses, and 88.2% (n = 15) had stable disease. No patient experienced progressive disease before surgery or an increase in lesion size; the median observed tumor shrinkage was 13.5% (range: 0%–33%). The estimated 12-month disease-free survival (DFS) probability was 94% (95% confidence interval [CI], 65–99); the estimated 24-month DFS probability was 88% (95% CI, 61–97). There were no grade 4/5 treatment-related adverse events. Correlative blood and tissue analyses showed changes in the TME, resulting in an immunologically active tumor by the time of surgery (median time to surgery was 50 days).
RADICAL CYSTECTOMY VERSUS TRIMODAL THERAPY FOR MUSCLE-INVASIVE BLADDER CANCER
This multi-institutional, retrospective analysis (2005–2017) included patients with T2–T4N0M0 muscle-invasive urothelial carcinoma of the bladder (MIBC) who were eligible for radical cystectomy (RC) or trimodal therapy (TMT).[3] All patients had solitary tumor <7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ (CIS). In the propensity score analysis, the 3:1 matched cohort included 1119 patients (837-RC, 282-TMT). After matching, age, sex, cT2 stage, presence of hydronephrosis, and receipt of neoadjuvant or adjuvant chemotherapy were similar between groups. The median follow-up was 4.38 years (interquartile range: 1.6–6.7) versus 4.88 years (2.8–7.7), respectively. There were no differences in 5-year metastasis-free survival (74% [95% CI 70–78] vs. 75% [70–80]), 5-year cancer-specific survival (81% [95% CI 77–85] vs. 84%), and 5-year disease-free survival (73% [95% CI 69–77] vs. 74%) for RC and TMT, respectively. The overall survival (OS) favored TMT (66% [95% CI 61–71] vs. 73% [68–78]; hazard ratio [HR] 0.70 [95% CI 0.53–0.92]; P = 0·010). Thus, this multi-institutional study provides the best evidence to date showing comparable oncological outcomes. TMT should be offered to select patients with MIBC with multidisciplinary shared decision-making, and not only to patients with significant comorbidities where RC is not an option.
THE ABLATIVE EFFECT OF MITOMYCIN REVERSE THERMAL GEL FOR LOW-GRADE UPPER TRACT TRANSITIONAL CELL CARCINOMA
Mitomycin C, formulated as a reverse thermal gel (UGN-101), polymerizes at the body temperature after liquid instillation at lower temperatures and has a chemo-ablative effect that allows for a longer contact time.[4]
This retrospective study assessed if low-grade upper tract transitional cell carcinoma urothelial carcinoma (LG-UTUC) patients could undergo partial ablation or biopsy only at initial ureteroscopy (URS) and still be rendered disease-free (RDF) with the goal of avoiding nephroureterectomy.[5] One hundred and sixteen patients from 15 high-volume centers were included for analysis. At first post-UGN-101 URS, there were no differences in the RDF rates between those who were at the initial URS (pre-UGN-101) and had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%), or biopsy only (RDF: 66.7%) (P = 0.14). Analysis focusing on the tumor size (completely ablated, <1 cm, 1–3 cm, or >3 cm) before UGN-101 induction did not demonstrate significant differences in the RDF rates (P = 0.17). The results of this early real-world experience suggest that UGN-101 may play a role in the initial chemo-ablative cytoreduction of larger volume LG-UTUC that may not initially appear to be amenable to renal preservation.
OFF-CLAMP ROBOTIC PARTIAL NEPHRECTOMY ADDS NO ADVANTAGE
The Vattikuti Collective Quality Initiative database, for robot-assisted partial nephrectomy (RAPN, n = 2114), was analyzed to compare the perioperative and functional outcomes of off-clamp and on-clamp RAPN.[6] After propensity matching, 205 patients each were included in each group. The two groups were similar in terms of age, sex, body mass index, tumor size, multifocality, tumor side, nephrometry score, polar location of the tumor, surgical access, and preoperative hemoglobin, creatinine, and estimated glomerular filtration rate (eGFR).
The results showed no significant difference between the two groups in terms of intraoperative and postoperative complications. However, the off-clamp group had a higher rate of blood transfusion (2.9% vs. 0%, P = 0.318) and conversion to radical nephrectomy (10.2% vs. 1%, P < 0.001). The positive surgical margin rate, although higher in the on-clamp group, was not statistically significant (8.3% vs. 3.9%, P = 0.07). The median duration of follow-up in the off- and on-clamp RAPN were 19 and 17 months, respectively. There were no significant differences between the groups in terms of creatinine and eGFR, indicating similar renal function preservation. The EMERALD trial also echoed similar outcomes.[7]
RADIOMICS-BASED MACHINE LEARNING TO IMPROVE LYMPH NODE STAGING FOR BLADDER CANCER
The radiological definition of lymph node (LN)-positive disease is mainly based on the minimal axis diameter, morphology, heterogeneity, contrast enhancement, and texture, and is subject to experience-dependent interpretation.[8] Radiomics is an emerging field of medical image computing that might help in overcoming the limitations of the current radiological rating.[8]
Gresser et al. assessed the performance of quantitative radiomics signatures in detecting LN metastases in bladder cancer (BC).[9] A total of 391 BC patients who underwent RC with lymphadenectomy were included. The patients were divided into training and test cohorts. The manual and automated segmentations of pelvic LNs were performed, and radiomics features were extracted from each LN. A machine learning model was trained using histopathology labels as the ground truth. The results showed that the radiomics-based analysis using manual LN segmentation achieved an area under the curve (AUC) of 0.80 in the test cohort. In contrast, the automated segmentation had an AUC of 0.70, while the radiologist assessment had an AUC of 0.78. The combination of a manually segmented radiomics signature and radiologist assessment resulted in an AUC of 0.81. Therefore, the radiomics signature demonstrated high diagnostic accuracy in discriminating nodal status.
LONG-TERM SURVIVAL OUTCOMES OF BLADDER-SPARING TREATMENT IN BACILLUS CALMETTE–GUERIN-UNRESPONSIVE NONMUSCLE-INVASIVE BLADDER CANCER
Only short-term outcomes of bladder-sparing treatment (BST) in patients with bacillus Calmette–Guerin (BCG)-refractory nonmuscle-invasive BC (NMIBC) are reported with a 12-month disease-free rate of 24% and 24-month cystectomy-free rate of 65%.[10] Tan et al. aimed to evaluate the long-term survival results between individuals who received BST, early RC (eRC), and delayed RC.[11]
Their institutional NMIBC registry data between January 2000 and September 2021 were analyzed (n = 114). There were no significant changes in the overall survival or cancer-specific survival between eRC (n = 38) and BST (n = 76). At 60 months, BST patients had a 37% high-grade recurrence-free rate, 83% muscle-invasive/metastasis progression-free rate, and a 58% avoidance of RC rate. Multivariate analysis revealed that current smoking status, negative lymphovascular invasion (LVI), and/or variant histology were predictors of high-grade recurrence. This long-term survival analysis of BCG-unresponsive NMIBC patients undergoing BST suggests that it may be safe in patients without LVI and/or variant histology and nonsmokers and noninferior to those receiving eRC.
SURVIVAL OUTCOMES IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER UNDERGOING RADICAL VERSUS PARTIAL CYSTECTOMY
Chung et al. aimed to investigate the variations in survival for RC and partial cystectomy (PC).[12] From the National Cancer Database, 22,534 individuals with cT2-4 BC who underwent RC or PC (n = 1.457) from 2003 to 2015 were analyzed for the OS. RC had a longer median OS than PC (67.8 vs. 54.1 months; P = 0.002). However, a subgroup analysis of patients (n = 10.215), with cT2, cN0, tumor size <5 cm, and no concomitant CIS with only 6% undergoing PC, showed no difference in OS (RC = 65.7 and PC = 62.6 months, respectively) on multivariate Cox regression (HR: 1.02, 95% CI, 0.9–1.2, P = 0.74). The 5-year OS was 53% for RC versus 47% for PC. The event-free survival was statistically significant in this subgroup, favoring PC (HR: 0.73, 95% CI, 0.62–0.86, P < 0.001). Thus, in selected patients of MIBC, PC offers comparable survival results to RC. The National Comprehensive Cancer Network gives category 2A recommendations for PC after neoadjuvant chemotherapy for highly selected patients with a solitary lesion in a suitable location with no CIS.[7]
Footnotes
Financial support and sponsorship: Nil.
Conflicts of interest: There are no conflicts of interest.
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