SARIFA as a new histopathological biomarker is associated with adverse clinicopathological characteristics, tumor-promoting fatty-acid metabolism, and might predict a metastatic pattern in pT3a prostate cancer.

BACKGROUND: Recently, we introduced Stroma-AReactive-Invasion-Front-Areas (SARIFA) as a novel hematoxylin-eosin (H&E)-based histopathologic prognostic biomarker for various gastrointestinal cancers, closely related to lipid metabolism. To date, no studies on SARIFA, which is defined as direct tumor-adipocyte-interaction, beyond the alimentary tract exist. Hence, the objective of our current investigation was to study the significance of SARIFA in pT3a prostate cancer (PCa) and explore its association with lipid metabolism in PCa as lipid metabolism plays a key role in PCa development and progression. METHODS: To this end, we evaluated SARIFA-status in 301 radical prostatectomy specimens and examined the relationship between SARIFA-status, clinicopathological characteristics, overall survival, and immunohistochemical expression of FABP4 and CD36 (proteins closely involved in fatty-acid metabolism). Additionally, we investigated the correlation between SARIFA and biochemical recurrence-free survival (BRFS) and PSMA-positive recurrences in PET/CT imaging in a patient subgroup. Moreover, a quantitative SARIFA cut-off was established to further understand the underlying tumor biology. RESULTS: SARIFA positivity occurred in 59.1% (n = 178) of pT3a PCas. Our analysis demonstrated that SARIFA positivity is strongly associated with established high-risk features, such as R1 status, extraprostatic extension, and higher initial PSA values. Additionally, we observed an upregulation of immunohistochemical CD36 expression specifically at SARIFAs (p = 0.00014). Kaplan-Meier analyses revealed a trend toward poorer outcomes, particularly in terms of BRFS (p = 0.1). More extensive tumor-adipocyte interaction, assessed as quantity-dependent SARIFA-status on H&E slides, is also significantly associated with high-risk features, such as lymph node metastasis, and seems to be associated with worse survival outcomes (p = 0.16). Moreover, SARIFA positivity appeared to be linked to more distant lymph node and bone metastasis, although statistical significance was slightly not achieved (both p > 0.05). CONCLUSIONS: This is the first study to introduce SARIFA as easy-and-fast-to-assess H&E-based biomarker in locally advanced PCa. SARIFA as the histopathologic correlate of a distinct tumor biology, closely related to lipid metabolism, could pave the way to a more detailed patient stratification and to the development of novel drugs targeting lipid metabolism in pT3a PCa. On the basis of this biomarker discovery study, further research efforts on the prognostic and predictive role of SARIFA in PCa can be designed.

Predictive factors and oncological outcomes of pathological T3a upstaging in patients with clinical T1 renal cell carcinoma undergoing partial nephrectomy.

OBJECTIVES: To investigate predictive factors and oncological outcomes of pathological T3a upstaging in renal cell carcinoma patients who were initially diagnosed as clinical T1 and treated with partial nephrectomy. METHODS AND MATERIALS: The clinical records and survival data of 1617 patients, who had undergone partial nephrectomy for clinical T1 renal cell carcinoma at Tokyo Women's Medical University, Tokyo, Japan between January 2011 and December 2020, were analyzed retrospectively. RESULTS: Of 1617 clinical T1 renal cell carcinoma patients who underwent partial nephrectomy, 28 (1.73%) had pathological T3a upstaging. In the multivariable analysis for pathological T3a upstaging using logistic regression models, male sex and clinical T1b were significant factors associated with pathological T3a upstaging (male sex: odds ratio = 5.07, 95% confidence interval: 1.18-21.8, clinical T1b: odds ratio = 8.36, 95% confidence interval: 3.56-19.6). The Kaplan-Meier method of the recurrence-free survival showed shorter recurrence-free survival in patients with pathological T3a upstaging than in those with pathological T1 (P < 0.0001). In the multivariable analysis using Cox proportional hazards regression models, pathological T3a upstaging was no longer significantly associated with recurrence-free survival after adjustment for other pathological factors (hazard ratio = 1.59, 95% confidence interval: 0.58-4.36). In a sensitivity analysis that analyzed its components individually instead of whole pathological T3a, neither perinephric fat invasion, sinus fat invasion, nor renal vein invasion was associated with recurrence-free survival. CONCLUSIONS: Male sex and clinical T1b were significant predictors for pathological T3a upstaging after partial nephrectomy in clinical T1 renal cell carcinoma patients. Although patients with pathological T3a upstaging had worse recurrence-free survival compared with those without upstaging, multivariable analyses revealed that pathological T3a upstaging was not an independent predictor for poor recurrence-free survival.

Differential Prognostic Value of Extrarenal Involvement in Patients With Non-Metastatic Renal Cell Cancer.

INTRODUCTION: A better definition of the prognostic significance of non-metastatic pT3a stage RCC subcategories is crucial to select the best candidate for adjuvant treatment. The aim of the study is to investigate the differential prognosis of extrarenal involvement in patients with non-metastatic pT3a RCC. MATERIALSAND METHODS: From a single institutional prospective database, 451 consecutive patients treated for pT3aN0/NxM0 RCC were selected and stratified according to pT3a subtypes (perirenal fat invasion, sinus fat invasion, segmental/renal vein thrombus, ≥ 2 features). Cancer specific survival (CSS), metastasis free survival (MFS) and relapse free survival (RFS) were primary endpoints of multivariable Cox regression models. RESULTS: Overall, 67 (15%) patients presented with renal/segmental vein thrombus only, 185 (41%) with perirenal fat invasion, 101 (22%) with sinus fat invasion and 98 (22%) with ≥ 2 features. The presence of ≥ 2 pT3a features was associated with a higher risk of metastasis (HR=2.36; 95%CI 1.30-4.27; P value = .005), recurrence (HR=2.41; 95%CI 1.36-4.28; P value=.003) and cancer specific mortality (HR=3.54; 95%CI 1.45-8.63; P value = .005) compared to only 1 pT3a feature. Moreover, the presence of perirenal fat invasion was associated with lower CSS (HR=2.82; 95% CI 1.19-6.69; P value = .02) compared to sinus fat invasion or tumoral thrombus only. CONCLUSION: The concurrent presence of ≥ 2 pT3a features is associated to a higher risk of distant progression, relapse and cancer specific mortality, implying potential role for adjuvant therapy or a more stringent follow-up. Moreover, perirenal fat invasion is associated with worse CSS compared to other pT3a patterns taken alone.

Prognostic features of upstaged pT3a renal tumors with fat invasion after robot-assisted partial nephrectomy: is it time for a new subclassification?

INTRODUCTION: The clinical management of pT3a pathologic-upstaged renal cell carcinoma (RCC) patients is actually controversial. Aim of this study was i) to assess the impact of pT3a upstaging on oncologic outcomes after robot-assisted partial nephrectomy (RAPN) for cT1-T2 RCC; ii) to explore clinical and surgical predictors of pT3a upstaging; iii) to evaluate the differential impact of perinephric fat invasion (PFI) or sinus fat invasion (SFI) on survival outcomes after RAPN in case of upstaged pT3a RCC. MATERIALS AND METHODS: Clinical and surgical data from consecutive RCCs treated with RAPN in a single referral centre between January 2017 and June 2021 were prospectively collected and retrospectively reviewed. Pathological upstaging to pT3a tumors with fat invasion was further stratified in SFI or PFI. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of disease recurrence. RESULTS: Overall, 1852 patients were enrolled and 179 (9.7%) with pT3a upstaging were found. Median age was 65 (IQR 56-73) years with a median BMI of 25.6 (23.6-29.0). At a median follow up of 26 (9-38) months, 76 (4.1%) patients showed disease recurrence. Multivariable analysis confirmed PADUA score ≥10 (OR 1.76, CI 95% 1.18-1.91, p = 0.001), age at surgery (OR 1.04, CI 95% 1.01-1.06, p = 0.01), clinical tumor diameter (OR 1.31, CI 95% 1.17-1.47, p = 0.001), tumor necrosis (OR 1.54, CI 95% 1.08-1.88, p = 0.001) and nucleolar grading ≥3 (OR 1.27, CI 95% 1.01-1.44, p = 0.001) as independent predictors of pT3a upstaging. Multivariate Cox regression model showed pathological sinus fat invasion as an independent predictor of disease recurrence (HR 3.43, CI 95% 1.51-7.77, p = 0.003) in pT3a upstaged group. CONCLUSION: In pathologically upstaged pT3a RCCs, sinus fat invasion was confirmed as independent predictor of disease relapse. In this light, the definition of novel risk categories in the pT3a patients setting should be encouraged.

Oncologic outcomes and predictive factors for progression in pT3a renal cell carcinoma.

OBJECTIVES: We aimed to evaluate oncologic outcomes of pT3a renal cell carcinoma (RCC) patients that treated with radical or partial nephrectomy and identify clinical or pathological factors that predict local recurrence or metastasis. METHODS: In this single center, retrospective study, we evaluated medical records of 856 patients who underwent radical or partial nephrectomy for RCC. Patients who had pT3aN0M0 RCC in final pathology and at least 6 months of follow-up included in the study. Patients' demographic characteristics, laboratory parameters, tumor characteristics and oncological outcomes were recorded. Cancer specific and overall survivals were our primary outcomes. Multivariate analysis was performed to identify factors affecting oncologic outcomes. RESULTS: A total of 86 pT3aN0M0 RCC patients were included final analysis of our study. During the mean 60.75 months follow up, 3 patients (3.5%) had experienced local recurrence and 19 patients (22.1%) had experienced metastasis. Total of 24 patients (27.9%) had died during the follow up. In this population 10-year OS was 70.8%, 10-year PFS was 61.3% and 10-year CSS was 78.4%. In multivariate analysis, chronic renal failure (CRF) was an independent worse prognostic factor for overall survival (p=0.03). Besides this sarcomatoid differentiation was an independent prognostic factor for PFS, CSS and OS (p=<0.001). CONCLUSIONS: Our study investigated the predictive factors for worse oncologic outcomes in pT3aN0M0 RCC patients. Although many factors have predictive value in univariate analysis, only sarcomatoid differentiation have independent predictive value for worse CSS, PFS and OS. Besides sarcomatoid differentiation, CRF is an independent prognostic factor for poor OS.

Oncological Outcomes of Patients With Different Pathological Features of pT3a Renal Tumor: A Systematic Review and Quantitative Synthesis.

PURPOSE: To identify the differences in oncological outcomes for patients with different pT3a renal tumor invasion patterns and pathological features. METHODS: The protocol of this study was registered on PROSPERO (CRD42021234475). Relevant studies were identified by searching the PubMed, Cochrane library, Embase, and Web of Science databases. Cancer-specific survival (CSS) was selected as the endpoint. Pooled hazard ratio (HR) and 95% confidence interval (CI) extracted from multivariate Cox models were evaluated to identify the hazard association. RESULTS: A total of 22 studies, which enrolled 12384 patients were included for quantitative synthesis. Sinus fat invasion (SFI) + perinephric fat invasion (PFI) was associated with inferior CSS compared to SFI only (p = 0.02). Comparable CSS was observed between SFI and PFI (p = 0.57). SFI ± PFI showed inferior CSS compared to PFI only (p = 0.0002). The presence of pelvicalyceal system invasion significantly increased the risk of cancer-specific mortality (p = 0.0005). Renal vein invasion (RVI) indicated poor oncological outcomes in terms of CSS (p = 0.002). The concomitant RVI and fat invasion (FI) significantly increased the risk of deterioration of CSS compared to RVI or FI (p < 0.0001). Multiple invasion patterns translated into a significantly decreased CSS (p < 0.0001). Aggressive tumor behavior, including lymph node involvement (p = 0.006), distant metastases (p < 0.00001), sarcomatoid differentiation (p < 0.0001), necrosis (p < 0.0001), Fuhrman grade III or IV (p < 0.0001), positive margin (p < 0.0001), and tumor size >7cm (p < 0.0001) were the predictors of inferior CSS. The lymphovascular invasion (p = 0.67) was indolent in terms of CSS. CONCLUSION: This study confirmed the heterogenicity of pT3a renal tumors. Multiple invasion patterns could translate into a significantly decreased CSS, and SFI should not be merged in the SFI + PFI group. The presence of PSI or RVI could significantly increase the risk of cancer-specific mortality. Lymph node involvement, distant metastases, sarcomatoid differentiation, necrosis, high Fuhrman grade, positive margin, and size >7cm were the predictors of inferior CSS. A precise-risk grade of CSS for different invasion patterns including comprehensive combinations may be useful for the further refinements of the TNM system. SYSTEMATIC REVIEW REGISTRATION: The current study was registered on PROSPERO, and the registration numbers is CRD42021234475.

A meta-analysis for comparison of partial nephrectomy vs. radical nephrectomy in patients with pT3a renal cell carcinoma.

BACKGROUND: Kidney cancer is the most common malignant tumor of the kidney in adults. However, in terms of the treatment for pT3a renal cell carcinoma (RCC), whether partial nephrectomy (PN) can be selected is still controversial. This study was conducted to compare the efficacy of PN and radical nephrectomy (RN) in treatment for patients with pT3a RCC. METHODS: The relative English databases including PubMed and EMBASE were searched for studies comparing PN and RN for pT3a RCC between 2010 and 2020. Stata 13.0 software was used to compare the cancer-specific survival (CSS), overall survival (OS), cancer-specific mortality (CSM), relapse-free survival (RFS), complications and positive surgical margin. RESULTS: Nine articles were included with a total of 3,391 patients, of whom 2,113 received RN and 1,278 received PN. The results showed that there is no statistical difference in CSS, OS, CSM, RFS, complications and positive surgical margin between RN and PN. No heterogeneity was shown in study. CONCLUSIONS: There were no differences in the CSS, OS, CSM, RFS, complications and positive surgical margin of the patients in RN and PN group. For pT3a RCC, RN did not provide a better survival benefit compared to PN. Considering PN can suppress the progression of tumor and reduce the risk of postoperative chronic renal insufficiency, we found PN is a good choice for pT3a RCC. However, further large-sample, studies are still needed in future.

The prognostic value of fat invasion and tumor expansion in the hilar veins in pT3a renal cell carcinoma.

PURPOSE: The 7th TNM classification summarizes renal cell carcinoma (RCC) with perirenal (PFI) and/or sinus fat invasion (SFI) as well as hilar vein involvement (RVI) as pT3a tumors. In this study, we aimed to determine the prognostic value of fat invasion (FI) in the different compartments and RVI for medium-term cancer-specific-survival (CSS) in pT3a RCC. MATERIALS AND METHODS: Patients with pT3a RCC were identified using an institutional database. All original pathological reports were reclassified according to the 7th TNM edition. The prognostic value of FI as well as divided into PFI, SFI, combined PFI + SFI, and RVI for CSS was assessed using univariate and multivariate Cox-regression analysis. Survival was estimated using the Kaplan-Meier method. RESULTS: Median follow-up in 184 pT3a tumors was 38 months. FI was detectable in 153 patients (32.7% PFI, 45.1% SFI, 22.2% PFI + SFI), 31 patients showed RVI alone. Combined PFI + SFI increased the risk of cancer-related death compared to PFI (HR 3.11, p < 0.01), SFI (HR 1.84, p = 0.023) or sole RVI (HR 2.12, p = 0.025). In multivariate analysis, a combined PFI + SFI vs. PFI or SFI as the only compartment involved was confirmed as independent prognostic factor (HR 1.83, p = 0.029). Patients with FI and simultaneous RVI had significantly shorter CSS (HR 2.63, p < 0.01). In an unweighted model, the difference between patients with combined PFI + SFI and RVI and those with PFI alone was highest (HR 4.01, p = 0.029). CONCLUSIONS: These results underline the subdivision of pT3a RCC depending on the location of FI and RVI for patient stratification.

Upstaging to pT3a in Patients Undergoing Partial or Radical Nephrectomy for cT1 Renal Tumors: A Systematic Review and Meta-analysis of Outcomes and Predictive Factors.

CONTEXT: Predictors of upstaging from cT1 to pT3a renal masses are poorly inquired, and this remains an area of controversial findings. OBJECTIVE: To evaluate predictors and outcomes of upstaging from cT1 to pT3a in patients undergoing surgical removal of a renal tumor. EVIDENCE ACQUISITION: A systematic literature search was performed to identify relevant articles using three electronic engines (PubMed, Embase, and Web of Science). Only studies looking at upstaging to pT3a in patients undergoing either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1 renal tumor were included. Study selection was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. EVIDENCE SYNTHESIS: Thirteen studies, including 21869 patients (cT1/pT3a: 1256 [5.7%]; cT1/pT1: 20613 [93.3%]), were identified. Patients in the upstaged group were older (weighted mean difference [WMD]: 3.89; p < 0.00001) and mostly male (odds ratio [OR]: 1.23; p = 0.04). Renal tumors were larger (WMD: 0.98; p < 0.00001), more complex (OR: 2.38; p < 0.0001), and with a higher rate of cT1b masses (OR: 3.36; p < 0.00001). The cT1/pT3a group had a higher rate of other renal cell carcinoma histological subtypes (OR: 1.59; p = 0.04), as well as higher odds of Fuhrman grade ≥3 (OR: 2.57; p < 0.00001) and positive surgical margins (OR: 1.85; p = 0.007). Five-year recurrence-free survival (RFS) was worse in the upstaged group (OR: 0.31; p = 0.02). Age (OR: 1.03; p < 0.00001), tumor size (OR: 1.51; p < 0.00001), and RENAL score (OR: 2.80; p = 0.0004) were predictors of upstaging. Upstaging was associated with overall survival (hazard ratio [HR]: 1.94; p = 0.05), cancer-specific survival (HR: 2.24; p = 0.007), and RFS (HR: 2.17; p < 0.00001). CONCLUSIONS: Upstaging to pT3a in case of surgical removal of a cT1 renal tumor is an uncommon event, which however can translate into worse oncological outcomes. Both patient (older age) and tumor (larger size and higher complexity) characteristics are associated with a higher risk of upstaging. There is very limited evidence regarding whether RN would be better than PN in these cases. There remains an unmet need for tools to better characterize renal masses in the preoperative setting. PATIENTS SUMMARY: About 6% of surgically treated localized renal tumors can be found to be locally advanced on final pathology after surgery. This "upstaging" can translate into worse oncological outcomes. There are patient and tumor characteristics that are associated with an increased the risk of upstaging.

Prognostic value of perirenal and/or sinus fat infiltration in patients with pT3a renal cell carcinoma: A multicentre cohort study. LARCG Group. / Valor pronóstico de la invasión de grasa perirrenal y/o del seno en pacientes con carcinoma de células renales pT3a: estudio de cohorte multicéntrico. Grupo LARCG.

INTRODUCTION AND OBJECTIVES: The objective of this study is to evaluate overall survival (OS), cancer-specific survival (CSS), relapse-free survival, local and distant (LRFS and DRFS, respectively) rates in patients with pT3a renal cell carcinoma (RCC) considering the perirenal and/or sinus fat infiltration (FI) as prognostic factors. MATERIALS AND METHODS: Retrospective cohort of patients with pT3a RCC who underwent radical or partial nephrectomy. The data were extracted from the LARCG (Latin American Renal Cancer Group) database. The demographic, clinical, pathological and surgical variables were evaluated. FI was divided into 4 groups (vein, perirenal, sinus and both fats infiltration). The Kaplan Meier and Cox regression curves were performed. RESULTS: 293 patients were included in the study. The mean age was 61.4 years. The median follow-up was 21 months (r: 1-194). CSS, RFS, LRFS and DRFS estimated at 3 years in the group of both fats' infiltration were 53.1, 45.1, 58.7 and 51.6 months, respectively, and always statistically lower than the rest (P˂0.005). In the multivariate analysis, the infiltration of both fats significantly increased specific mortality, overall and local relapse with respect to vein infiltration (HR: 4.5, 2.42 and 8.08, respectively). The Fuhrman grade and renal pelvis infiltration were independent predictors of CSS and RFS. CONCLUSIONS: Infiltration of both fats increases the risk of overall and local relapse in pT3a RCC. In the same way, it is associated with a lower cancer-specific survival and should be considered as a factor of poor prognosis.

Oncological outcomes and pathological characteristics of cT1 upstaging to pT3a renal cell carcinoma compared with de novo pT3a tumors. / Resultados oncológicos y características patológicas de la sobrestadificación de cT1 a carcinoma de células renales pT3a en comparación con los tumores pT3a de novo.

INTRODUCTION: The significance of upstaging of cT1 renal tumors to pT3a is not clear. We evaluate the incidence of upstaging, identify predictors and analyze oncological outcomes of these patients versus those who did not upstage. We also compared the oncological outcomes of cT1 upstaging to pT3a with de novo pT3a renal tumors. METHODS: From a database of 1021 renal tumors with complete available follow-up data, 517 patients had cT1. Patients upstaging to pT3a were compared to those who did not. Baseline clinical, perioperative, histopathologic features and oncological outcomes were analysed. RESULTS: Out of 517 cT1 patients, 105 (20.3%) upstaged to pT3a and 412 (79.7%) did not. Proportion of patients in each group undergoing partial and radical nephrectomy, postoperative tumor size, histology, margin status and lymph node involvement were similar. Among upstaged, 9 patients (8.6%) developed first recurrence as compared to only 3 (0.7%) in those not upstaging (P <0.001). The median time to recurrence (57 vs. 107 months; P <0.001) was lesser in de novo pT3a renal tumors. CONCLUSIONS: Pathological upstaging from cT1 to pT3a and necrosis on histopathology were associated with recurrence. Advanced age, smoking, necrosis on histopathology, clear cell histology and higher Fuhrman grades contributed to pathological upstaging of cT1 tumors. De novo pT3a RCC had worse survival when compared to cT1 patients upstaging to pT3a RCC.

Association between renal mass biopsy and upstaging to perinephric fat involvement in a contemporary cohort of patients with clinical T1a renal cell carcinoma.

BACKGROUND: Although tumor tract seeding from renal mass biopsy (RMB) is exceedingly rare, the possibility of tumor capsule violation from RMB leading to perinephric fat invasion has not been quantified. We evaluated the association between RMB and perinephric fat invasion in patients with clinical T1a renal cell carcinoma who underwent partial or radical nephrectomy. MATERIALS AND METHODS: We reviewed the National Cancer Database from 2010-2013 and identified patients who underwent surgery for clinical T1a tumors. Patients were classified as upstaged only if final pathology demonstrated perinephric invasion only (pT3a). Mixed-effect logistic regression analysis was performed on inverse probability weighted matched groups to identify predictors of perinephric fat invasion. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate overall survival (OS). RESULTS: A total of 24,548 patients met our inclusion criteria. Pathologic upstaging to pT3a perinephric fat involvement occurred in 1.2% of patients. This rate of upstaging was 1.1% in the no biopsy group compared with 2.1% in patients who underwent RMB (P < 0.01). In multivariable logistic model, RMB was associated with pT3a perinephric fat upstaging (OR 1.69, 95% CI 1.17-2.44, P < 0.01). Upstaging to pT3a was also associated with worse OS (HR 1.71, 95% CI 1.13-2.60, P = 0.01). Kaplan-Meier survival curves demonstrated similar OS estimates in patients upstaged to pT3a disease, irrespective of undergoing RMB or not (Log-Rank = 0.87). CONCLUSION: RMB was associated with increased rate of upstaging to pT3a perinephric fat involvement in clinical T1a RCC. This effect is small with unclear clinical significance. This is perhaps balanced by the importance of the information acquired from biopsies. Future studies are needed to elucidate clinical significance of this finding.

Perioperative morbidity, oncological outcomes and predictors of pT3a upstaging for patients undergoing partial nephrectomy for cT1 tumors.

OBJECTIVES: To evaluate perioperative morbidity, oncological outcome and predictors of pT3a upstaging after partial nephrectomy (PN). MATERIALS AND METHODS: Retrospective study of 1042 patients who underwent PN for cT1N0M0 renal cell carcinoma between 2007 and 2015. A total of 113 cT1 patients were upstaged to pT3a, while 929 were staged as pT1. Demographic, perioperative and pathological variables were reviewed. We compared the clinico-pathological characteristics, perioperative morbidity and oncological outcomes between pT3a and pT1 groups. Multivariate regression evaluates variables associated with T3a upstaging. Recurrence-free survival (RFS) and overall survival analyses were performed. Survival curves were compared using log-rank test. RESULTS: The pT3a tumors were high complexity tumors (median RENAL score 8 vs. 7, p < 0.01), higher hilar (h) location (27.5 vs. 14.8%, p < 0.01), higher grade (57.5 vs. 38.2%, p < 0.01), and higher positive surgical margins (18.6 vs. 5.8%, p < 0.01. Patients with pT3a had a higher estimated blood loss, transfusion rate, ischemia time and overall complications, though there were no differences in median e-GFR decline and major (Grade III-V) complications. Five-year RFS was 78.5% for pT3a group vs. 94.6% for pT1 group (log-rank p < 0.01). Male gender (OR 2.2, p < 0.01), and R.E.N.A.L. score (OR 2.3, p = 0.01) were preoperative predictors of upstaging. We acknowledge limitations in our study, most are inherent problems of retrospective studies. CONCLUSION: Perioperative morbidity, after partial nephrectomy, is acceptable in cT1/pT3 tumors in comparison to cT1/pT1; however, upstaged patients had a worse oncological outcome. cT1/pT3a tumors are associated with adverse clinico-pathological features. Preoperative risk predictors of upstaging were higher R.E.N.A.L. score and male gender.