A better understanding of the molecular basis of urothelial carcinoma (UC) is needed to refine the clinical decision-making process. We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC) and urinary bladder UC (UBUC) were compared. Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P=.137). In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%). Frequently detected somatic mutations included TP53 (68.5%), KDR (41.3%), and PIK3CA (17.4%). Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P=.020). The most common types of CNVs included amplifications (56/62, 90.3%): 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4) fusion. Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.

Radical prostatectomy (RP) is the main treatment of prostate cancer (PCa). Biochemical recurrence (BCR) following RP remains the first sign of aggressive disease; hence, better assessment of potential long-term post-RP BCR-free survival is crucial. Our study aimed to evaluate a combined clinical-deep learning (DL) model using multiparametric magnetic resonance imaging (mpMRI) for predicting long-term post-RP BCR-free survival in PCa. A total of 437 patients with PCa who underwent mpMRI followed by RP between 2008 and 2009 were enrolled; radiomics features were extracted from T2-weighted imaging, apparent diffusion coefficient maps, and contrast-enhanced sequences by manually delineating the index tumors. Deep features from the same set of imaging were extracted using a deep neural network based on pretrained EfficentNet-B0. Here, we present a clinical model (six clinical variables), radiomics model, DL model (DLM-Deep feature), combined clinical–radiomics model (CRM-Multi), and combined clinical–DL model (CDLM-Deep feature) that were built using Cox models regularized with the least absolute shrinkage and selection operator. We compared their prognostic performances using stratified fivefold cross-validation. In a median follow-up of 61 months, 110/437 patients experienced BCR. CDLM-Deep feature achieved the best performance (hazard ratio [HR] = 7.72), followed by DLM-Deep feature (HR = 4.37) or RM-Multi (HR = 2.67). CRM-Multi performed moderately. Our results confirm the superior performance of our mpMRI-derived DL algorithm over conventional radiomics.

Lee CH, et al. J Korean Med Sci. 2024 Sep;39:e293. https://doi.org/10.3346/jkms.2024.39.e293

Background: The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair cross-complementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer. Methods: A retrospective analysis was performed on 93 patients with completely resected transitional cell carcinoma of the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1 expression was analyzed in 57 patients treated with adjuvant gemcitabine plus cisplatin chemotherapy and 36 who were not treated. Results: Among 93 patients, ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1 positivity was significantly associated with longer survival (adjusted hazard ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the group without adjuvant chemotherapy while ERCC1 positivity was associated with shorter survival among patients who have received adjuvant chemotherapy (adjusted hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical benefit from adjuvant chemotherapy was associated with ERCC1 negativity as measured by overall survival (test for interaction, P = 0.034) and by disease-free survival (test for interaction, P = 0.20). Conclusions: Among patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors. Future prospective, randomized studies are warranted to confirm our findings.

We determined the effects of warm ischemia time on the recovery of renal function after partial nephrectomy under pneumoperitoneum. In this prospective study 37 consecutive patients who underwent laparoscopic partial nephrectomy or robot-assisted partial nephrectomy between June 2008 and May 2009 to remove a single cT1 renal tumor were evaluated using ^99mTc-diethylenetriamine pentaacetic acid renal scintigraphy preoperatively, and at 3 and 12 months postoperatively. The most significant reduction in the glomerular filtration rate of the affected kidney at 3 and 12 months after surgery (p = 0.018, p = 0.036, respectively) was seen for a warm ischemia time cutoff of 28 minutes. The glomerular filtration rate of the affected kidney was consistently and significantly reduced at 3 and 12 months postoperatively (−22.4% to −30.6%, p <0.001) in patients with a warm ischemia time greater than 28 minutes. In contrast, no significant glomerular filtration rate change was seen in patients with a warm ischemia time of 28 minutes or less. In terms of the contributional change of the affected kidney to total renal function, there is a trend toward a recovery after an initial decrease in both groups with a warm ischemia time greater than 28 minutes vs 28 minutes or less. On multivariate analysis warm ischemia time was a strong independent predictor of glomerular filtration rate reduction even 12 months after surgery (β = −1.3; 95% CI −1.8, −0.7; p <0.001). If the warm ischemia time is greater than 28 minutes during laparoscopic partial nephrectomy or robot-assisted partial nephrectomy, the functional damage to the affected kidney progresses even up to 1 year after surgery.