Urologic Oncology-seminars and Original Investigations最新文献

Background and objective: For patients with metastatic testicular cancer undergoing retroperitoneal lymph node dissection (RPLND), the burden of metastatic disease can require consideration for resection and replacement of major vessels despite chemotherapy. We aimed to clarify the outcomes for patients undergoing these major vascular procedures in a modern era.

Methods: Between 2000 and 2020, 2,054 patients with metastatic testicular cancer underwent a PC-RPLND; of those men, 41 also underwent an aortic, iliac, and/or inferior vena cava (IVC) resection. For men who required a vascular resection, clinicopathologic and operative details were collected. Kaplan-Meier curves were generated to estimate overall survival.

Results: The median preoperative mass size was 9cm in the retroperitoneum. Viable malignancy or teratoma was present in 85% of resected specimens. Following PC-RPLND and vascular resection, 22 (54%) patients recurred. The median (IQR) time to relapse was 4.6 (2.5-8.0) months. 18 (44%) patients died of disease. The overall complication rate was 56%. Ten (24%) patients had Clavien-Dindo III/IV complications, with 2 postoperative mortalities. The median overall survival was 14.9 months. Among the 41 patients, 18 patients had re-operative PC-RPLND and vascular resection; the re-operative PC-RPLND patients had significantly worse survival compared to initial attempt at PC-RPLND (9.3 vs. 162 months, P = 0.03).

Conclusions: The overall survival rate for patients undergoing PC-RPLND with resection of the aorta, IVC, and/or iliac artery is 45% at 2 years. For patients with limited treatment options, these complex surgeries may offer survival benefit with an acceptable morbidity profile.

Background: Androgen receptor signaling inhibitors (ARSIs) have revolutionized the treatment of metastatic castration-sensitive prostate cancer (mCSPC). Prostate-specific antigen (PSA) dynamics, including PSA nadir, PSA response rate, and time to PSA nadir (TTN), are well-established markers of disease control. We evaluated the clinical significance of these PSA dynamics using data from a multicenter clinical database for mCSPC patients.

Methods: We conducted a multicenter retrospective study including 552 mCSPC patients treated with ARSI and ADT, and 262 patients treated with combined androgen blockade (CAB). PSA nadir, PSA response rate, and TTN were evaluated using predefined cut-offs. Clinicopathological data were collected and subsequently analyzed using multivariate Cox regression models to investigate impact of the PSA dynamics on oncological outcomes, including castration resistant prostate cancer free survival (CRPCFS), cancer-specific survival (CSS), and overall survival (OS). Propensity score matching (PSM) was used to minimize selection bias and balance baseline characteristics between treatment the groups. The achievement rates of low PSA nadir and high PSA response were then evaluated.

Results: In the ARSI cohort, 36.4% of patients achieved a PSA nadir of ≤ 0.02 ng/mL, and 65.8% attained a PSA response rate of ≥ 99 %. Notably, patients with a PSA nadir of ≤ 0.02 ng/mL, a PSA response rate ≥ 99%, and TTN > 12 months demonstrated significantly improved oncological outcomes. Multivariate analyses confirmed that these PSA dynamics were independent predictors of favorable oncological outcomes. A PSA nadir of ≤ 0.02 ng/mL was as an independent predictor of improved oncological outcomes compared to a nadir of > 0.2 ng/mL (CRPCFS: HR, 0.063; CSS: HR, 0.12; OS: HR, 0.15; P < 0.001). A PSA response rate of ≥ 99% compared to < 95%, also independently predicted more favorable outcomes (CRPCFS: HR, 0.29; CSS: HR, 0.26; OS: HR, 0.30; P < 0.001). Furthermore, a TTN > 12 months was also an independent predictor of improved survival compared to TTN ≤ 3 months (CRPCFS: HR, 0.12; CSS: HR, 0.08; OS: HR, 0.12; P < 0.001). PSM with a 1:1 ratio was associated with significantly higher rates of PSA nadir ≤ 0.02 ng/mL and PSA response rate ≥ 99% in the ARSI doublet group compared to the CAB group.

Conclusions: Our study demonstrates that achieving a PSA nadir ≤ 0.02 ng/mL, a PSA response rate ≥ 99%, and a longer TTN are associated with significantly improved oncological outcomes. Furthermore, we elucidated how PSA dynamics differ between ARSI doublet therapy and CAB, highlighting the distinct characteristics of each. These findings provide valuable clinical information for guiding the management and prognosis of mCSPC in routine clinical practice.

Introduction: The trigone/urethra (T/U) has a distinct embryologic origin and a different histologic morphology compared to the rest of the urinary bladder. We sought to determine the association between tumors involved in the T/U and the presence of variant histology, pathologic, and oncologic outcomes in patients who underwent robot-assisted radical cystectomy (RARC).

Methods: Tumor location was classified into 2 groups: tumors in the bladder walls only, or tumors in the T/U area, with or without involvement of other bladder walls. Univariable and multivariable Cox regression models were used to determine the association between T/U with recurrence-specific (RSS), cancer-specific (CSS), and overall survival (OS).

Results: 608 patients who underwent RARC were identified, T/U involvement occurred in 191 (31%). Patients in the T/U group were more likely to have pT3/pT4 (57% vs. 42%, P < 0.01), positive surgical margins (21% vs. 9%, P < 0.01), and received salvage chemotherapy more frequently (16% vs. 8%, P < 0.01). Squamous variant histology was more frequent in the T/U group (25% vs. 17%, P = 0.02). On multivariable analysis, T/U location was independently associated with RSS (HR1.63, 95% CI 1.23-2.16, P < 0.01) and CSS (HR1.50, 95% CI 1.04-2.16, P = 0.02) but not OS.

Conclusion: Residual T/U tumor involvement was associated with a higher risk of an advanced tumor stage, positive margin, cancer recurrence, and cancer-specific death.

Objective: Carcinogenic mechanisms of heavy metals/ trace elements (HMTE) in bladder cancer (BC) are exactly unknown. Mitochondrial dysfunction (MD), oxidative stress (OS), and mitogen-activated protein kinases (MAPK) are probable carcinogenic mechanisms. The purpose is to investigate probable carcinogenic pathways of HMTE in BC using six MD genes, seven OS markers, and p38-MAPK.

Methods: Study included 125 BC/radical cystectomy (RC) patients between October 2020 and October 2022, and 72 controls. Exclusion criteria included previous neoplasm, chemo- or radiotherapy. Two samples (cancer/noncancer) were taken from RC specimens. Tissues/plasma/urine cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), strontium (Sr), aluminium (Al), zinc (Zn), boron (B) were measured by ICP-OES. Tissue MD genes (mt-CO3, mt-CYB, mt-ATP 6, mt-ATP8, mt-CO1, mt-ND1), and serum OS markers (8-OHdG, MDA, 3-NT, AGEs, AOPP, ROS, SOD2), p38-MAPK were assessed by RT-PCR, and ELISA, respectively.

Results: BC and adjacent tissue showed higher (Al, Co, Pb, Ni, Zn, Cd,Sr), lower B concentrations, compared to controls. High tissue concentrations (Cd, Co, Pb, Ni, Sr) were associated with higher MD genes, OS, MAPK and lower SOD2 levels. The same differences were greater in 41 patients with concomitant elevation of two or more HMTE. Noninclusion of BC-related oncogenes (e.g. RAS) is a limitation.

Conclusions: Evidence suggests that high BC tissue (Cd, Co, Pb, Ni, Si) concentrations are associated with over-expressed MD genes, OS, p38-MAPK and low SOD2. These findings provide important understanding keys of probable carcinogenic pathways in BC associated with HMTE. So, efforts should be performed to minimize and counteract exposure to toxic HMTE.

Introduction: Single-port (SP) robotic surgical system performs well in small anatomical spaces, which makes it suitable for retroperitoneal robotic partial nephrectomy (RPN). However, there is limited evidence comparing the safety and feasibility of SP RPN to multiport (MP) RPN. To address this gap in evidence, we sought to analyze and compare the safety of retroperitoneal RPN between SP and MP approaches.

Methods: This is a retrospective cohort study using data from the Single Port Advanced Research Consortium (SPARC) and a multicenter database of patients who underwent retroperitoneal RPN using either SP or MP between 2017 and 2023. Baseline, perioperative, and postoperative data were compared using t-tests, Mann-Whitney U test, χ² test, and Fisher exact test. Multivariable analyses were conducted using robust and Poisson regressions.

Results: A total of 286 patients (SP RPN, n = 86 [30%]; MP RPN, n = 200 [70%]) underwent retroperitoneal RPN. R.E.N.A.L nephrometry score and tumor location were significantly different between the 2 groups. Notably, the ischemia time was significantly shorter in the MP group (16 vs. SP, 22 minutes, P < 0.001). Adjusting for baseline characteristics, the ischemia time was approximately 7.89 minutes longer for patients in the SP group compared to the MP group, on average (95% CI: 5.87, 9.92; P < 0.001). No significant differences were observed in operative time, EBL, blood transfusion, conversion rates, LOS, PSM, and overall 30-day postoperative complications between the 2 groups.

Conclusion: Our study shows that retroperitoneal SP and MP RPN have comparable perioperative and postoperative outcomes, except for the longer ischemia time in the SP platform. SP RPN is a safe and viable alternative; however, further research is needed to explore its potential benefits, cost-effectiveness, and long-term oncologic outcomes.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.

Purpose: To develop and validate a clinicoradiomics model based on intratumoral habitat imaging for preoperatively predicting of progression-free survival (PFS) of clear cell renal cell carcinoma (ccRCC) and analyzing progression-associated genes expression.

Methods: This retrospective study included 691 ccRCC patients from multicenter databases. Entire tumor segmentation was performed with handcrafted process to generate habitat subregions based on a pixel-wise gray-level co-occurrence matrix analysis. Cox regression models for PFS prediction were constructed using conventional volumetric radiomics features (Radiomics), habitat subregions-derived radiomics (Rad-Habitat), and an integration of habitat radiomics and clinical characteristics (Hybrid Cox). Training (n = 393) and internal validation (n = 118) was performed in a Nanjing cohort, external validation was performed in a Wuhan and Zhejiang cohort (n = 227) and in a TCGA-KIRC (n =71) with imaging-genomic correlation. Statistical analysis included the area-under-ROC curve analysis, C-index, decision curve analysis (DCA) and Kaplan-Meier survival analysis.

Results: Hybrid Cox model resulted in a C-index of 0.83 (95% CI, 0.73-0.93) in internal validation and 0.79 (95% CI, 0.74-0.84) in external validation for PFS prediction, higher than Radiomics and Rad-Habitat model. Patients stratified by Hybrid Cox model presented with significant difference survivals between high-risk and low-risk group in 3 data sets (all P < 0.001 at Log-rank test). TCGA-KIRC data analysis revealed 37 upregulated and 81 downregulated genes associated with habitat imaging features of ccRCC. Differentially expressed genes likely play critical roles in protein and mineral metabolism, immune defense, and cellular polarity maintenance.