Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond

PurposeDuring COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival.Materials and methodsWe retrospectively abstracted cT1b-T2bN0M0 RCC patients from the National Cancer Database, stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within 1 month, 1–3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed overall survival.ResultsA total of 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR = 0.90; 95% CI: 0.77–1.05, P = 0.170), cT2a (OR = 0.90; 95% CI: 0.69–1.19, P = 0.454), or cT2b (OR = 0.96; 95% CI: 0.62–1.51, P = 0.873). In all clinical stage strata, nonclear cell RCCs were significantly less likely to be upstaged (P <0.001). A sensitivity analysis, performed for delays of <1, 1–3, 3–6, and >6 months, also showed no increase in upstaging risk.ConclusionDelaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered.     

Resultados oncológicos y características patológicas de la sobrestadificación de cT1 a carcinoma de células renales pT3a en comparación con los tumores pT3a de novo

IntroductionThe 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.MethodsFrom 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.ResultsOut 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.ConclusionsPathological 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.     

Machine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15)

Objectives

To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging.

Materials and Methods

Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours.

Results

A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9).

Conclusions

Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes.     

Upstaging to pT3a disease in patients undergoing robotic partial nephrectomy for cT1 kidney cancer: Outcomes and predictors from a multi-institutional dataset

ObjectivesSurgically treated clinical T1 (cT1) kidney cancer has in general a good prognosis, but there is a risk of upstaging that can potentially jeopardize the oncological outcomes after partial nephrectomy (PN). Aim of this study is to analyze the outcomes of robot-assisted PN (RAPN) for cT1 kidney cancer upstaged to pT3a, and to identify predictors of upstaging.Material and methodsThe study cohort included 1,640 cT1 patients who underwent RAPN between 2005 and 2018 at 10 academic institutions. Multivariate logistic regression model was used to assess the predictors of upstaging. Kaplan-Meier curves and multivariable Cox regression analyses were used to evaluate recurrence-free survival and overall survival.ResultsOverall, 74 (4%) were upstaged cases (cT1/pT3a). Upstaged patients presented larger renal tumors (3.1 vs. 2.4 cm; P = 0.001), and higher R.E.N.A.L. score (8.0 vs. 6.0; P = 0.004). cT1/pT3a group had higher rate of intraoperative complications (5 vs. 1% P = 0.032), higher pathological tumor size (3.2 vs. 2.5 cm; P < 0.001), higher rate of Fuhrman grade ≥3 (32 vs. 17%; P = 0.002), and higher number of sarcomatoid differentiation (4 vs. 1%; P = 0.008). Chronic kidney disease (CKD) stage ≥3 (OR: 2.54; P < 0.014), and clinical tumor size (OR: 1.07; P < 0.001) were independent predictors of upstaging. cT1/pT3a group had worse 2-year (94% vs. 99%) recurrence-free survival (P < 0.001).ConclusionsUpstaging to pT3a in patients with cT1 renal mass undergoing RAPN represents an uncommon event, involving less than 5% of cases. Pathologic upstaging might translate into worse oncological outcomes, and therefore strict follow-up protocols should be applied in these cases.     

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.

Prognostic significance of indeterminate lung nodules in renal cell carcinoma

ObjectivesMany patients with renal cell carcinoma (RCC) are found to have lung nodules at the time of diagnosis. The significance of these nodules is unclear. This study sought to determine whether the presence of indeterminate lung nodules affects survival for patients with early-stage RCC.Methods and materialsA retrospective review was performed of patients with stages I to III RCC at an academic hospital who underwent nephrectomy between 2001 and 2006 and had baseline imaging available for review. Presence of lung nodule(s) was determined, along with patient and disease characteristics. The time from diagnosis to last known follow-up, metastasis, and death were determined. The study follow-up period extended to July 2012. Univariate and multivariate Cox proportional hazards models assessed disease-free and overall survival.ResultsOf 548 patients, 240 met the inclusion criteria. Lung nodules were absent in 148 and present in 92 cases. Disease-free survival was associated with the presence of nodules (hazard ratio [HR] = 1.90; 95% CI: 1.04–3.46; P = 0.0362), tumor stage (stage II—HR = 5.61; 95% CI: 2.69–11.72; P<0.001 and stage III—HR = 2.49; 95% CI: 1.21–5.10; P = 0.0129) and tumor grade (HR = 2.43 for grades 3 or 4; 95% CI: 1.31–4.53; P = 0.005). The number and size of nodules were not associated with survival. Overall survival was associated with Charlson comorbidity score (HR = 1.30; 95% CI: 1.15–1.47; P<0.0001) and primary tumor size (HR = 1.29; 95% CI: 1.14–1.46; P<0.0001) but not the presence of lung nodules (HR = 1.73; 95% CI: 0.83–3.60; P = 0.1454).ConclusionsThe presence of indeterminate lung nodules had a negative effect on disease-free survival. Stage and grade were also significant. These findings underscore the importance of baseline imaging and vigilant surveillance of patients in whom nodules are identified.     

Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis

PURPOSETyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC.MATERIALS AND METHODSThe MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade.RESULTSFive trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81–0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83–1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10–6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22–12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity.CONCLUSIONSThe findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.     

Pathological upstaging of clinical T1 renal cell carcinoma: an analysis of 115,835 patients from National Cancer Data Base, 2004–2013

Purpose

Clinical staging is vital for treatment decision-making by renal cell carcinoma (RCC) patients. Some RCCs clinically appear T1 on CT, but are actually T3a due to extension into fat or renal vein, causing the tumor to be pathologically upstaged. The objective of this study to determine the rate, survival, and predictors of RCC upstaging, for patients with cT1 disease treated surgically.

Methods

Using the National Cancer Data Base Participant User File for RCC from 2004 to 2013, we selected AJCC cT1 patients, who underwent surgical resection and whose AJCC pathological T stage (pT) was available. Upstaging was characterized dichotomously—overall (any pT > T1) and pT3a-specific upstaging. Patient and tumor characteristics of those upstaged and not were compared using Chi-squared analyses. Multivariable logistic regression was used to analyze predictors of upstaging, and Cox proportional hazards regression was used to estimate overall survival hazards ratios.

Results

Overall upstaging (pT > T1) was observed in 8252 (7.1%) patients, and T3a-specific upstaging was observed in 3380 (5.4%) patients. Patients who were older, male, and had comorbidities, and tumors that were cT1b, underwent RN, and had high Fuhrman grade were at a higher risk of pathological upstaging. Upstaging led to a 40% increased risk of death compared to patients who were not upstaged.

Conclusion

The rate of upstaging is not negligible (5–7% of the time), negatively impacts survival, and various patient and tumor characteristics can be used to predict upstaging.

     

Increased preoperative levels of plasma fibrinogen and d dimer in patients with renal cell carcinoma is associated with poor survival and adverse tumor characteristics

Background and objectiveThe relationship between renal cell carcinoma (RCC) and coagulation/fibrinolysis system has been described in several studies. The aim of this study was to investigate the role of 4 different coagulation/fibrinolysis factors on the prediction of histopathologic and survival prognosis in patients with RCC.Patients and methodsData from 128 patients who underwent surgical intervention between March 2006 and January 2011 for RCC were evaluated in this prospective study. Blood samples were collected from all patients on the morning of the operation to measure the plasma fibrinogen, d-dimer, coagulation factor VII, and antithrombin 3 levels. The relationships of these factors in the demographic, clinical, and histopathologic outcomes were analyzed using the Student t, Mann-Whitney U, Kruskal-Wallis, and one-way analysis of variance tests. Receiver operating curve analyses were performed to determine the optimal cutoff level for fibrinogen and d dimer, both of which had a strong relation with the clinical and histopathologic parameters. Disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method. Multivariate Cox regression analyses (forward stepwise logistic regression) were performed to examine the independent prognostic values on survival outcomes.ResultsIncreased plasma fibrinogen and d-dimer levels were associated with tumor size (P = 0.004 and 0.106), nuclear grade (P<0.001 and<0.001), TNM category (P<0.001 and 0.029), and metastasis (P<0.001 and 0.032). Both increased plasma fibrinogen and d-dimer levels predicted decreased DFS (P = 0.027 and 0.04), CSS (P = 0.007 and 0.043), and OS (P = 0.014 and 0.001) rates based on Kaplan-Meier analyses. Furthermore, multivariate analyses demonstrated that fibrinogen independently predicted poor DFS (hazard ratio [HR] = 2.52; 95% CI: 1.04–6.31; P = 0.029) and CSS (HR = 3.89; 95% CI: 1.13–13.40; P = 0.032), whereas d dimer had negative independent prognostic value on OS (HR = 4.01; 95% CI: 1.54–10.50; P = 0.005).ConclusionsIncreased plasma fibrinogen levels accurately predict poor histopathologic and survival outcomes and may be an effective independent prognostic factor in patients with RCC. Moreover, d dimer may serve as a copredictive factor in conjunction with fibrinogen.     

Prognostic nutritional index and prognosis in renal cell carcinoma: A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis of the Prognostic Nutritional Index (PNI) as a prognostic factor for renal cell carcinoma (RCC).Materials and methodsEligible studies that evaluated the prognostic impact of pretreatment PNI in RCC patients were identified by comprehensive searching the electronic databases PubMed, Cochrane Central Search library, and EMBASE. The end points were overall/cancer-specific survival (OS/CSS) and recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs).ResultsIn total, 9 retrospective, observational, case-control studies involving 5,976 patients were included for final analysis. Eight studies evaluated OS/CSS, and 5 evaluated RFS/DFS. Our results showed that lower PNI was significantly associated with unfavorable OS/CSS (HR = 1.68, 95% CI 1.44-1.96, P < 0.001, I² = 9.2%, P = 0.359) and RFS/DFS (HR = 1.98, 95% CI 1.57-2.50, P < 0.001, I² = 18.2%, P = 0.299) in patients with RCC. Subgroup and meta-regression analysis based on ethnicity, study sample size, presence of metastasis, PNI cut-off value, Newcastle–Ottawa quality assessment scale (NOS) score, and gender ratio all showed that lower PNI was associated with poorer OS/CSS and RFS/DFS. Funnel plots and Egger's tests indicated significant publication bias in OS/CSS (P = 0.001), but not in RFS/DFS (P = 0.757).ConclusionThis meta-analysis indicated that lower PNI was a negative prognostic factor and associated with tumor progression and poorer survival of patients with RCC. Therefore, PNI could be a potential prognostic predictor of treatment outcomes for patients with RCC.     

Does renal tumor biopsies for small renal carcinoma increase the risk of upstaging on final surgery pathology report and the risk of recurrence?

BackgroundRenal tumor biopsies (RTB) have been proposed as a means to diminish overtreatment of small renal masses. A potential concern of RTB is tumor seeding along the biopsy tract leading to worse clinical outcomes.ObjectivesTo evaluate whether RTB was associated with greater upstaging to pT3a compared to patients without a biopsy and to determine if pathologic upstaging affects the risk of recurrence.Design, setting and participantsThe Canadian Kidney Cancer information system was used to identify patients who underwent radical or partial nephrectomy for malignant renal tumors ≤ 4cm (cT1a) between January 1, 2011 and July 2, 2019.InterventionRTB prior to nephrectomy or nephrectomy without biopsy.Outcomes measurements and statistical analysisUpstaging to pT3a and cancer recurrence were compared between subjects that had a RTB compared to those who did not. A multivariable analysis was used to evaluate factors associated with disease upstaging and recurrence.Results and limitationsThe cohort consisted of 1993 cT1a patients, followed for a median of 17.5 months. Of these patients, 502 (25%) had a preoperative RTB. There was no difference in the proportion with tumor upstaging to pT3a between patients that had RTB compared to those who did not (7.2% vs. 6.3%; P = 0.5). On multivariable analysis, RTB was not associated with pathological upstaging (Odds Ratio 0.90; 95% Confidence Interval 0.61–1.34) or recurrence (Odds Ratio 1.04; 95% Confidence Interval 0.57–1.89). The main limitation is that the study is underpowered to detect small differences between groups.ConclusionsIn this large, multi-institution cohort, RTB was not associated with increased risk of tumor upstaging or recurrence. Hence, tumor tract seeding, although possible, should not be a clinical deterrent to using RTBs as a means of personalizing renal masses management and diminishing overtreatment.Patient summaryRecent evidence suggests that tumor seeding following RTB may be more common than initially perceived. Our results have demonstrated that RTB was not associated with an increased risk of tumor upstaging or disease recurrence.     

Functional and oncological outcome of percutaneous cryoablation versus laparoscopic partial nephrectomy for clinical T1 renal tumors: A propensity score-matched analysis

PurposeTo evaluate the clinical trifecta of percutaneous cryoablation (PCA) vs. laparoscopic partial nephrectomy (LPN) for cT1 renal tumors.Patients and methodsWe retrospectively analyzed the records of patients who had undergone 2 types of nephron sparing surgeries (NSS) PCA or LPN for cT1 renal tumors between November 2011 and December 2019. The cohorts were matched by one-to-one propensity scores based on patient demographics, renal function, and tumor complexity. Perioperative and oncological outcomes and preservation of renal function following surgery were compared.ResultsAfter matching, a total of 180 patients who had undergone NSS for de novo renal tumors were evaluable: 90 for PCA and 90 for LPN. No statistically significant differences were noted among the measured baseline characteristics in the propensity score-matched cohorts. Overall perioperative complication rates were 5.5% in the PCA and 11.1% in the LPN groups (P = 0.28). The rate of eGFR preservation 1 to 3 months after surgery was significantly higher for PCA than for LPN (92.8 ± 11.5% vs. 88.5 ± 14.6%, P = 0.03). Median follow-up was 33 months for PCA and 18 months for LPN (P < 0.001). Three residual and 4 recurrent tumors were later diagnosed in the PCA group and 1 recurrent tumor in the LPN group. The 5-year local recurrence-free survival was lower for PCA than LPN (90.2% vs. 98.5%, P = 0.36). The 5-year metastasis-free survival rate was similar in both groups (98.4% vs. 100%, P = 0.38). The 5-year overall and cancer-specific survival rates were comparable in both groups (91.7% vs. 98.9%, P = 0.53, and 95% vs. 100%, P = 0.55, respectively).ConclusionsClinical T1 RCC patients are better treated with LPN if technically possible. Though PCA had a higher local recurrence rate, medium-term local control was not inferior to LPN. Additionally, PCA patients tended to retain renal function without severe complications. PCA appears to be a reasonable option for patients with high comorbidity at presentation.     

Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy

ObjectiveTo evaluate the prognostic effect of concomitant variant histology (CVH) on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy.Materials and methodsData on 417 patients with UTUC treated with radical nephroureterectomy without preoperative adjuvant therapy were retrospectively reviewed with a focus on CVH. Clinicopathological features and prognostic factors were compared between patients with pure UTUC and patients with UTUC with CVH. The primary end points were cancer-specific survival (CSS), disease recurrence-free survival (DFS), and overall survival (OS).ResultsUTUC with CVH was present in 90 (21.6%) of 417 patients. At a median follow-up of 26 months, 153 (36.7%) had died of UTUC, 161 (38.6%) had experienced a relapse, and 176 (42.2%) had died of other causes. UTUC with CVH was significantly associated with advanced tumor stage, high tumor grade, tumor diameter, lymphovascular invasion, lymph node metastasis, positive surgical margins, and tumor architecture compared with pure UTUC (all P<0.01). The estimated 5-year CSS, DFS, and OS rates were 64.9%, 61.1%, and 62.1%, respectively, in the pure UTUC group, compared with 36.3%, 34.3%, and 26.5%, respectively, in the UTUC with CVH group (P<0.001). Multivariate analysis demonstrated that CVH was an independent predictor of CSS (hazard ratio [HR] = 1.594; 95% CI: 1.125–2.259; P = 0.009), DFS (HR = 1.549; 95% CI: 1.077–2.152; P = 0.017), and OS (HR = 1.685; 95% CI: 1.212–2.343; P = 0.002).ConclusionsApproximately one-fifth of the specimens of patients with UTUC were observed to exhibit CVH. CVH was an independent prognostic factor for CSS, DFS, and OS in patients with UTUC on both univariate and multivariate analyses. Genitourinary pathologists should look for potential CVH components in UTUC specimens and report this in routine pathological practice. The presence of CVH should identify patients as candidates for consultation regarding early adjuvant therapy and intensive surveillance protocols.     

Evaluation of PD-L1 (E1L3N, 22C3) expression in venous tumor thrombus is superior to its assessment in renal tumor in predicting overall survival in renal cell carcinoma

BackroundRenal cell carcinoma (RCC) frequently invades renal vein forming neoplastic thrombus. The expression of immune checkpoint receptors in RCC was addressed in multiple studies, but little is known about the expression and prognostic significance of programmed death ligand-1 in tumor thrombus.Material and methodsThe study aimed to evaluate the expression of PD-L1 within venous tumor thrombus and primary tumor using 2 independent antibody clones (22c3 and E1L3N) and to assess its value in predicting overall survival (OS) in the subgroup of patients with RCC and renal vein thrombus.ResultsEighty-two patients with RCC and venous tumor thrombus that underwent nephrectomy were enrolled. The expression of PD-L1 was assessed utilizing tissue microarrays separately on tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). The frequency of PD-L1 expression on TCs and TILs varied between tumor and thrombus compartments and was dependent on the antibody clone used. The expression of PD-L1 on TCs and/or TILs was associated with worse OS irrespectively of the antibody and the analyzed compartment. Nevertheless, the best prognostic performance was noted for the combined assessment of PD-L1 expression on TCs and TILs in venous tumor thrombus with the use of 22c3 antibody. The multivariable Cox regression model predicting OS incorporated PD-L1 22c3 in venous tumor thrombus (hazards ratio [HR] = 3.64, 95% confidence interval [CI] = 1.63–8.14, P = 0.002) and nodal status (HR = 2.88, 95% CI = 1.18–7.03, P = 0.02).ConclusionsPD-L1 may become a valuable tool for prognostic purposes in this specific subgroup of patients and be incorporated into the respective models qualifying for adjuvant treatment.     

Presurgical sunitinib reduces tumor size and may facilitate partial nephrectomy in patients with renal cell carcinoma

ObjectiveTo determine whether presurgical sunitinib reduces primary renal cell carcinoma (RCC) size and facilitates partial nephrectomy (PN).MethodsData from potential candidates for PN treated with sunitinib with primary RCC in situ were reviewed retrospectively. Primary outcome was reduction in tumor bidirectional area.ResultsIncluded were 72 potential candidates for PN who received sunitinib before definitive renal surgery on 78 kidneys. Median primary tumor size was 7.2 cm (interquartile range [IQR]: 5.3–8.7 cm) before and 5.3 cm (IQR: 4.1–7.5 cm) after sunitinib treatment (P<0.0001), resulting in 32% reduction in tumor bidirectional area (IQR: 14%–46%). Downsizing occurred in 65 tumors (83%), with 15 partial responses (19%). Tumor complexity per R.E.N.A.L. score was reduced in 59%, with median posttreatment score of 9 (IQR: 8–10). Predictors of lesser tumor downsizing included clinical evidence of lymph node metastases (P<0.0001), non–clear cell histology (P = 0.0017), and higher nuclear grade (P = 0.023). Surgery was performed for 68 tumors (87%) and was not delayed in any patient owing to sunitinib toxicity. Grade≥3 surgical complications occurred in 5 patients (7%). PN was performed for 49 kidneys (63%) after sunitinib, including 76% of patients without and 41% with metastatic disease (P = 0.0026). PN was completed in 100%, 86%, 65%, and 60% of localized cT1a, cT1b, cT2, and cT3 tumors, respectively.ConclusionPresurgical sunitinib leads to modest tumor reduction in most primary RCC, and many patients can be subsequently treated with PN with acceptable morbidity and preserved renal function. A randomized trial is required to definitively determine whether presurgical therapy enhances feasibility of PN.     

Cellular hyaluronan is associated with a poor prognosis in renal cell carcinoma

PurposeHyaluronan, a major glycosaminoglycan of the extracellular matrix, can act as an oncogenic component of the tumor microenvironment in many human malignancies. We characterized the hyaluronan content of renal cell carcinomas (RCCs) and investigated its correlations with clinicopathological parameters and patient survival.Patients and methodsThis retrospective study included data from 316 patients that had undergone surgery for RCC in Kuopio University Hospital in 2000 to 2013. The hyaluronan content of surgical tumor samples were histochemically stained with a biotinylated hyaluronan-specific affinity probe. The amount of tumor infiltrating lymphocytes was evaluated in each tumor. Kaplan-Meier and univariate and multivariate Cox-regression analyses were performed to estimate the impact of hyaluronan content on overall survival, disease-specific survival, and metastasis-free survival.ResultsDetectable cellular hyaluronan was associated with higher tumor grades and the presence of tumor infiltrating lymphocytes. Cellular hyaluronan identified a prognostically unfavourable subgroup among low-grade carcinomas. Multivariate analyses showed that measurable cellular hyaluronan was an independent negative prognostic factor for overall survival (hazard ratio [HR] 1.4; 95% confidence interval [CI]: 1.02–2.0; P = 0.039), Disease-specific survival (HR 2.07; 95% CI: 1.2–3.3; P = 0.002), and metastasis-free survival (HR 2.45; 95% CI: 1.37–4.4; P = 0.003).ConclusionsCellular hyaluronan was significantly associated with unfavourable features and a poor prognosis in RCC. Further studies are needed to investigate the biological mechanism underlying hyaluronan accumulation in RCC.     

Percutaneous cryoablation versus partial nephrectomy for cT1b renal tumors: An inverse probability weight analysis

PurposeTo investigate differential clinical outcomes in patients treated with partial nephrectomy (PN) vs. percutaneous cryoablation (PCA) for cT1b renal tumors.Materials and methodsWe retrospectively analyzed the records of 119 patients who had undergone PN (n = 90) or PCA (n = 29) for cT1b renal tumors. Inverse probability weighting (IPW) was used for balancing patient demographics, including renal function and tumor complexity. Perioperative complications, renal function preservation rates, and oncological outcomes such as local recurrence-free, metastasis-free, cancer-specific, and overall survival were compared using IPW-adjusted restricted mean survival times (RMSTs).ResultsPCA was more likely to be selected for octogenarians (odds ratio: 11.4, 95% confidence interval [CI]: 3.33–45.1). During the median follow-up of 43 months in the PCA group and 36.5 months in the PN group, unablated local residue or local recurrence was noted in 6 patients in the PCA group and local recurrence was noted in 4 patients in the PN groups. Of the 6 patients in the PCA group, 4 underwent salvage PCA, and local control had been achieved at the last visit. In the IPW-adjusted population, PCA had significantly worse local recurrence-free survival compared with PN (IPW-adjusted RMST difference: -22.7 months, 95% CI: -45.3 to -0.4, P = 0.046). IPW-adjusted RMST for metastasis-free survival (P = 0.23), cancer-specific survival (P = 0.77), and overall survival (P = 0.11) did not differ between PCA and PN. In addition, PN was not a predictor for local control failure at the last visit (odds ratio: 0.30, 95%CI: 0.05–1.29). There were no statistically significant differences between PN and PCA in renal function preservation or overall/severe complication rates.ConclusionsIn patients with cT1b renal tumor, although the local recurrence rate is higher for PCA than for PN, PCA provides comparable distant oncologic outcomes. PCA can be an alternative treatment option for elderly, comorbid patients, even those with cT1b renal tumors.     

Race and sex disparities in the treatment of older patients with T1a renal cell carcinoma: A comorbidity-controlled competing-risks model

ObjectivesRecognizing population-level disparities for the treatment of patients with renal cell carcinoma (RCC) would inform clinical practice and health policy. Few studies, reporting conflicting results, have investigated race and sex disparities specifically among patients with small renal masses.Methods and materialsThe Surveillance, Epidemiology, and End Results-Medicare database (1995–2007) was queried for patients with localized T1a RCC undergoing radical nephrectomy, partial nephrectomy (PN), or deferred therapy (DT). Demographics, comorbidity, and treatment approach were assessed. Multivariable logistic regression models evaluated predictors of DT and then PN among those receiving surgery. Cox proportional hazards model evaluated survival differences for whites vs. blacks and women vs. men.ResultsA total of 6,092 white and 617 black patients with T1a RCC met the inclusion criteria. Blacks were twice as likely to defer therapy compared with whites (odds ratio = 1.95, 95% CI: 1.52–2.51) and had worse overall survival (hazard ratio = 1.36, 95% CI: 1.19–1.56). However, cancer-specific survival (CSS) was similar (P = 0.429). The greatest discrepancy was among healthy (Charlson comorbidity index≤1) blacks who had a much higher rate of DT compared with their white counterparts. Women were found to have decreased use of PN compared with men (odds ratio = 0.84, 95% CI: 0.74–0.96) and better CSS (hazard ratio = 0.74, 95% CI: 0.58–0.94), but there were no differences by race.ConclusionsThe differential use of DT by race instead of purely by age and comorbidity is concerning but has not led to a significant difference in CSS. Women are less likely to undergo PN compared with men, but they also have a notably improved CSS.     

Recurrence pattern in localized RCC: results from a European multicenter database (RECUR)

IntroductionThe impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern.Material and methodsThis is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed.ResultsAfter matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18–3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01–1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64–1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study.ConclusionsThe risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.     

Presence of lymphovascular invasion in urothelial bladder cancer specimens after transurethral resections correlates with risk of upstaging and survival: A systematic review and meta-analysis

ObjectivesThis study aimed to elucidate the relationship between lymphovascular invasion (LVI) at transurethral resection of bladder tumor (TURBT) and the risk of pathologic upstaging as well as the clinical outcomes.Materials and methodsPubMed, Scopus, Web of Science, and Cochrane Library databases were searched from the respective dates of inception until November 11, 2013.ResultsA total of 16 articles met the eligibility criteria for this systematic review, which included a total of 3,905 patients. LVI was detected in 18.6% of TURBT specimens. A significant association was found between LVI at TURBT and pathologic upstaging of bladder cancer (odds ratio = 2.21, 95% CI: 1.44–3.39) without heterogeneity (I² = 45%, P = 0.14). The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (HR = 1.47, 95% CI: 1.24–1.74), progression-free survival (HR = 2.28, 95% CI: 1.45–3.58), and disease-specific survival (HR = 1.35, 95% CI: 1.01–1.81), but not for overall survival (HR = 1.55, 95% CI: 0.90–2.67). Tests of inconsistency for disease-specific survival (I² = 66%, P = 0.007) and overall survival (I² = 72%, P = 0.03) could not exclude a significant heterogeneity. The results of the Begg and the Egger tests showed that there was evidence of publication bias on pathologic upstaging and progression-free survival.ConclusionsThe data obtained in this meta-analysis indicate that the presence of LVI at TURBT portends the increased risk of pathologic upstaging and may provide additional prognostic information. However, a large, well-designed, prospective study is needed to investigate potential treatment options for bladder cancer with LVI.