Although metastasis of clear cell renal cell carcinoma (ccRCC) is predominantly observed in late stage tumors, early stage metastasis of ccRCC can also be found with indefinite molecular mechanism, leading to inappropriate clinical decisions and poor prognosis. Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in calcium/phosphate homeostasis, which regulates various cellular processes in normal development and tumorigenesis. This study aimed to investigate the role and mechanism of regulation of STC1 in the metastasis of early stage ccRCC. STC1 mRNA and protein expression was determined in ccRCC surgical specimens, RCC cell lines, and human kidney tubule epithelial cell line HKC by real-time polymerase chain reaction (RT-PCR) and western blotting. Immunohistochemistry staining (IHC) and immunofluorescence were also used to examine the expression and localization of STC1 in ccRCC tissues and cancer cells. Knockdown and overexpression studies were conducted in vitro in RCC cell lines using small interfering RNAs (siRNA) and lentiviral-mediated gene delivery to evaluate the role of STC1 in cell proliferation, anchorage-dependent and independent growth, cell cycle control, and migration and invasion. STC1 mRNA and protein expression were significantly up-regulated in tumors when compared with non-tumor tissues, with the greatest increase in expression observed in metastatic tissues. Clinicopathological analysis revealed that STC1 mRNA expression was associated with Fuhrman tumor grade (P = 0.008) and overall Tumor Node Metastasis (TNM) staging (P = 0.018). STC1 expression was elevated in T1 stage metastatic tumors when compared with localized tumors, and was positively correlated with average tumor diameter. Silencing of STC1 expression by Caki-1 and A498 resulted in the inhibition of cell proliferation, migration, and invasion, meanwhile down-regulation of STC1 impaired epithelial–mesenchymal transition (EMT) of ccRCC cell lines. Overexpression of STC1 in Caki-2 enhanced cell growth and proliferation but not migration and invasion. Further investigation identified hypoxia and HIF-1α as candidate regulators of STC1 expression. Our findings demonstrate a role for STC1 in metastasis of early stage ccRCC and suggest that STC1 may be a biomarker of potential value both for the prognosis of this disease and for guiding clinical decisions regarding surgical strategies and adjuvant treatment.

Background: To compare perioperative, functional and oncological outcomes between transperitoneal robotic partial nephrectomy (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN). Methods: A literature searching of Pubmed, Embase, Cochrane Library and Web of Science was performed in August, 2020. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were estimated using fixed-effect or random-effect model. Publication bias was evaluated with funnel plots. Only comparative studies with matched design or similar baseline characteristics were included. Results: Eleven studies embracing 2,984 patients were included. There was no significant difference between the two groups regarding conversion to open (P = 0.44) or radical (P = 0.31) surgery, all complications (P = 0.06), major complications (P = 0.07), warm ischemia time (P = 0.73), positive surgical margin (P = 0.87), decline in eGFR (P = 0.42), CKD upstaging (P = 0.72), and total recurrence (P = 0.66). Patients undergoing TRPN had a significant higher minor complications (P = 0.04; OR: 1.39; 95% CI, 1.01–1.91), longer operative time (P < 0.001; WMD: 21.68; 95% CI, 11.61 to 31.76), more estimated blood loss (EBL, P = 0.002; WMD: 40.94; 95% CI, 14.87 to 67.01), longer length of hospital stay (LOS, P < 0.001; WMD: 0.86; 95% CI, 0.35 to 1.37). No obvious publication bias was identified. Conclusion: RRPN is more favorable than TRPN in terms of less minor complications, shorter operative time, less EBL, and shorter LOS. Methodological limitations of the included studies should be considered while interpreting these results.

The discrepant concordance between biopsy and radical prostatectomy (RP) specimen are well reported. To validate the clinical usefulness of neutrophil-lymphocyte ratio (NLR) in discriminating real GS ≥ 7 PCa from biopsy-based GS ≤ 6 PCa in comparison with serum total prostate-specific antigen (tPSA) and value of their combination. One hundred one patients who underwent physical examinations incidentally found elevated tPSA and subsequently received biopsy with a conclusion of GS ≤ 6 and RP with an interval of 4-6 weeks after biopsy were enrolled. NLR and tPSA were obtained within 15 days prior to biopsy. Logistic regression model was applied appropriately; McNemar tests and AUC model were performed to evaluate differences among tPSA, NLR and their combination and corresponding diagnostic power respectively. The pathological results from RP specimen comprised 61 patients with GS ≤ 6 and 100 patients with GS ≥ 7. Higher tPSA and NLR were significantly associated with patients with actual GS ≥ 7 (All P < 0.05) concurrently. Multivariate logistic regression indicated that tPSA (OR = 1.088, 95% C.I. = 1.029-1.151, P = 0.003) and NLR (OR = 1.807, 95% C.I. = 1.021-3.200, P = 0.042) could be independent predictors for GS groupings. Under cutoff value of 14.09 ng/ml for tPSA and 2.25 for NLR, the sensitivity, specificity and accuracy were 60.0%, 80.3% and 67.7% for tPSA, 42%, 88.5% and 59.6% for NLR, and 71.0%, 75.4% and 72.7% for combination of tPSA and NLR (tPSA + NLR) respectively. The sensitivity of tPSA + NLR was significantly higher in comparison with tPSA (P = 0.001) and NLR (P < 0.001). Except for sensitivity, no significant difference was found between tPSA and NLR in specificity (P = 0.227) and accuracy (P = 0.132). tPSA got the largest AUC with 0.732 (p < 0.001, 95% C.I.: 0.651-0.813). Serum tPSA and NLR were significantly elevated among GS ≥ 7 PCa concurrently. The combination of tPSA and NLR might have additional benefit to biopsy on discriminating real GS ≥ 7 Pca from biopsy-based GS ≤ 6 PCa. More stratification models and prospectively multicenter studies are necessary.

(1) Background: For completely lower pole renal tumors, we compared the perioperative outcomes of robotic partial nephrectomy via transperitoneal and retroperitoneal approaches. (2) Methods: Complete lower pole renal tumors were defined as tumors that received 1 point for the “L” element of the R.E.N.A.L. and located at the lower pole of kidney. After confirming consistency in baseline characteristics, oncological and functional benefits were compared. Pentafecta achievement was used to represent the perioperative optimal outcome, followed by multivariate analysis of factors associated with the lack of pentafecta achievement. (3) Results: Among 151 patients identified, 116 (77%) underwent robotic partial nephrectomy via a transperitoneal approach and 35 (23%) via a retroperitoneal approach. Patients undergoing transperitoneal robotic partial nephrectomy experienced more blood loss than those undergoing retroperitoneal robotic partial nephrectomy (50 mL vs. 40 mL, p = 0.015). No significant differences were identified for operative time (120 min vs. 120 min), ischemia time (19 min vs. 20 min), positive surgical margins (0.0% vs. 2.86%), postoperative rate of complication (12.07% vs. 5.71%). No significant differences were identified in pathologic variables, eGFR decline in postoperative 12-month (3.9% vs. 5.4%) functional follow-up. Multivariate cox analysis showed that tumor size (OR: 0.523; 95% CI: 0.371–0.736; p < 0.001) alone was independently correlated to the achievement of pentafecta. (4) Conclusions: For completely lower pole renal tumors, transperitoneal and retroperitoneal robotic partial nephrectomy provide similar outcomes. These two surgical approaches remain feasible options for these cases.

Background: Accurate prognostication of oncological outcomes is crucial for the optimal management of patients with renal cell carcinoma (RCC) after surgery. Previous prediction models were developed mainly based on retrospective data in the Western populations, and their predicting accuracy remains limited in contemporary, prospective validation. We aimed to develop contemporary RCC prognostic models for recurrence and overall survival (OS) using prospective population-based patient cohorts and compare their performance with existing, mostly utilized ones. Methods: In this prospective analysis and external validation study, the development set included 11 128 consecutive patients with non-metastatic RCC treated at a tertiary urology center in China between 2006 and 2022, and the validation set included 853 patients treated at 13 medical centers in the USA between 1996 and 2013. The primary outcome was progression-free survival (PFS), and the secondary outcome was OS. Multivariable Cox regression was used for variable selection and model development. Model performance was assessed by discrimination [Harrell’s C-index and time-dependent areas under the curve (AUC)] and calibration (calibration plots). Models were validated internally by bootstrapping and externally by examining their performance in the validation set. The predictive accuracy of the models was compared with validated models commonly used in clinical trial designs and with recently developed models without extensive validation. Results: Of the 11 128 patients included in the development set, 633 PFS and 588 OS events occurred over a median follow-up of 4.3 years [interquartile range (IQR) 1.7–7.8]. Six common clinicopathologic variables (tumor necrosis, size, grade, thrombus, nodal involvement, and perinephric or renal sinus fat invasion) were included in each model. The models demonstrated similar C-indices in the development set (0.790 [95% CI 0.773–0.806] for PFS and 0.793 [95% CI 0.773–0.811] for OS) and in the external validation set (0.773 [0.731–0.816] and 0.723 [0.731–0.816]). A relatively stable predictive ability of the models was observed in the development set (PFS: time-dependent AUC 0.832 at 1 year to 0.760 at 9 years; OS: 0.828 at 1 year to 0.794 at 9 years). The models were well calibrated and their predictions correlated with the observed outcome at 3, 5, and 7 years in both development and validation sets. In comparison to existing prognostic models, the present models showed superior performance, as indicated by C-indices ranging from 0.722 to 0.755 (all P<0.0001) for PFS and from 0.680 to 0.744 (all P<0.0001) for OS. The predictive accuracy of the current models was robust in patients with clear-cell and non-clear-cell RCC. Conclusions: Based on a prospective population-based patient cohort, the newly developed prognostic models were externally validated and outperformed the currently available models for predicting recurrence and survival in patients with non-metastatic RCC after surgery. The current models have the potential to aid in clinical trial design and facilitate clinical decision-making for both clear-cell and non-clear-cell RCC patients at varying risk of recurrence and survival.