Can microRNAs be utilized as tumor markers for recurrence following nephrectomy in renal cell carcinoma patients? A meta-analysis provides the answer

IntroductionRenal cell carcinoma (RCC) is an aggressive tumor. Many studies investigated microRNAs (miRs) as RCC prognostic biomarkers, often reporting inconsistent findings. We present a meta-analysis to identify if tissue-derived miRs can be used as a prognostic factor in patients after nephrectomy.MethodsData were obtained from PubMed, Embase, and Web of Science. The hazard ratio with 95% confidence intervals assessed the prognostic value of microRNAs. Outcomes of interest included the prognosis role of microRNAs in overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) in nephrectomy patients.ResultsNine retrospective studies that evaluated microRNAs in 1,541 nephrectomy patients were collected. There were heterogeneities across studies for microRNAs in the 15 studies examining OS, RFS, and CSS (I² = 84.51%; P < 0.01); the random-effect model was calculated (HR = 1.371; (95% CI: 0.831–2.260); P = 0.216).ConclusionOur study indicated that miRNAs cannot be used as a marker for recurrence in RCC patients after nephrectomy, and researchers shouldn't make the mistake that if miRs can be used as a biomarker in RCC, they cannot be used as a marker after nephrectomy in RCC. As all of these findings were from retrospective studies, further studies are needed to verify the role of microRNAs in clinical trials.     

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.     

Long-term outcomes after radical or partial nephrectomy for T1a renal cell carcinoma: A population-based study

IntroductionThe benefit of partial nephrectomy (PN) compared to radical nephrectomy (RN) for T1a renal cell carcinoma (RCC) remains uncertain, with observational studies conflicting with level 1 evidence. Therefore, the purpose of this population-based study was to compare long-term outcomes in patients undergoing PN or RN for T1a RCC.MethodsWe studied 5670 patients in Ontario, Canada undergoing PN or RN for T1a RCC. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), chronic kidney disease (CKD), renal replacement therapy, and myocardial infarction (MI). We used multivariable Cox proportional hazard models to evaluate the association between PN or RN and these outcomes. A sensitivity analysis was performed in patients with a preoperative serum creatinine available.ResultsMedian followup was 77 months. Compared to RN, PN was associated with significantly improved OS (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63–0.84), reduced risk of CKD (HR 0.18, 95% CI 0.12–0.27), and improved CSS (HR 0.45, 95% CI 0.30–0.65). The risk of MI was not significantly different between groups (HR 0.91, 95% CI 0.62–1.34). Few patients (n=15) required renal replacement therapy. In the sensitivity analysis, the association between type of surgery and OS and CKD persisted, while the association with CSS did not.ConclusionsOur study found that in patients undergoing surgery for T1a RCC, PN was associated with improved OS and reduced risk of CKD compared to RN. However, few patients in either group required renal replacement therapy.     

Development and internal validation of nomograms for the prediction of postoperative survival of patients with grade 4 renal cell carcinoma (RCC)

BackgroundTo develop successful prognostic models for grade 4 renal cell carcinoma (RCC) following partial nephrectomy and radical nephrectomy.MethodsThe nomograms were established based on a retrospective study of 135 patients who underwent partial and radical nephrectomy for grade 4 RCC at the Department of Urology, Peking University First Hospital from January 2013 to October 2018. The predictive performance of the nomograms was assessed by the calibration plot and C-index. The results were validated using bootstrap resampling.ResultsAspartate transaminase (AST), the maximum diameter of tumor (cutoff value =7 cm), lymph node metastasis, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were independent factors for determining the overall survival (OS) and cancer-specific survival (CSS) in multivariate analysis. AST, the maximum diameter of the tumor (cutoff value =7 cm), and lymph node metastasis were found to be independent variables for progression-free survival (PFS) in multivariate analysis. These variables were used for the studies to establish nomograms. All calibration plots revealed excellent predictive accuracy of the models. The C-indexes of the nomograms for predicting OS, CSS and PFS were 0.729 (95% CI, 0.659–0.799), 0.725 (95% CI, 0.654–0.796) and 0.702 (95% CI, 0.626–0.778), respectively. Moreover, the recurrence rate was not associated with open or laparoscopic radical nephrectomy in our cohort (P=0.126).ConclusionsWe have developed easy-to-use models that are internally validated to predict postoperative 1-, 3-, and 5-year OS, CSS, and PFS rates of grade 4 RCC patients. The new models could aid in identifying high-risk patients, making postoperative therapeutic and follow-up strategies as well as predicting patients’ survival after externally validated. Besides, our study shows that the recurrence rate is not associated with open or laparoscopic radical nephrectomy.     

术前血清胱抑素C水平对手术的肾癌患者预后的影响

目的探讨术前血清胱抑素C(Cystatin C,Cys-C)水平对肾癌患者预后的影响。方法回顾性分析2013年1月至2016年12月于徐州医科大学附属医院行根治性/部分肾切除术治疗的354例肾癌患者的临床病理和随访资料。根据受试者工作特征曲线(ROC)确定Cys-C的最佳临界值,将其分为高Cys-C组和低Cys-C组。运用Kaplan-Meier、Log-rank检验分析两组患者的总生存率和肿瘤特异性生存率的差异,通过单因素和多因素Cox模型分析影响患者总生存和肿瘤特异性生存的因素。结果共纳入354例患者,其中高Cys-C组36例、低Cys-C组318例。与低Cys-C组相比,高Cys-C组患者年龄更大、肿瘤分期更晚及尿素、肌酐、尿酸水平更高(P均<0.05),但肾小球滤过率相对较低(P<0.05)。Kaplan-Meier结果显示高Cys-C组与低Cys-C组5年总生存率分别为56.7%和96.2%,5年肿瘤特异性生存率分别为64.0%和96.5%(P均<0.05)。Cox多因素分析结果显示术前高Cys-C水平为肾癌患者术后总生存(HR:10.513,95%CI:2.539~43.522,P=0.001)和肿瘤特异性生存(HR:4.944,95%CI:1.017~24.043,P=0.048)的独立影响因素。结论肾癌患者术前血清Cys-C水平升高提示术后预后不良。     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Impact of the neutrophil-to-lymphocyte ratio as a surgical prognostic factor in renal cell carcinoma with inferior-vena-cava tumor thrombus

BackgroundThe aim of this study is to evaluate the efficacy of radical nephrectomy with thrombectomy and to identify the prognostic factors for patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus (IVCTT). The role of the neutrophil-to-lymphocyte ratio (NLR), which has been reported to be a useful prognostic predictor for various solid cancers, was also investigated.MethodsFifty-five patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy in our hospital were retrospectively analyzed. The relationship between clinical characteristics and surgical outcome was examined using the Kaplan–Meier method. Univariate and multivariate analyses were carried out to determine the prognostic factors.ResultsThe median follow-up time after surgery was 44.2 months. Twenty-seven patients died of RCC, and 4 died of other disease at last follow-up. There were no patients with postoperative pulmonary embolism (PE) or deaths from PE. The median cancer-specific survival (CSS) and overall survival (OS) were 81.0 (95% confidence interval [CI]: 42.0–103.2) and 69.0 (95% CI: 34.3–81.5) months, respectively. Significant prognostic factors for CSS were distant metastasis (p = 0.045) and NLR ≥ 2.9 (p = 0.009). The only independent predictor for OS was the NLR ≥ 2.9 (p = 0.034).ConclusionsA high preoperative NLR level was an independent poor prognostic factor influencing CSS and OS of patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy. The NLR may be an available biomarker that helps with preoperative risk stratification.     

Percentage of sarcomatoid histology is associated with survival in renal cell carcinoma: Stratification and implications by clinical metastatic stage

PurposeSarcomatoid dedifferentiation in renal cell carcinoma (RCC) represents an aggressive histology where degree of sarcomatoid histology (SH) may impact prognosis for cM0 and cM1 patients. We aimed to evaluate the association of percentage of SH with survival.Materials and methodsPatients ≥18 years old diagnosed with RCC with any degree of SH after nephrectomy were included (2005–2020) from a single-center. Associations of degree of SH and cM stage with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier curves and Cox proportional hazards regression.ResultsOne hundred twenty-eight patients were included with 80 (62.5%) cM0 and 48 (37.5%) cM1. cM1 patients were more likely to be male with higher clinical T stage (P = 0.001) than cM0, but a similar proportion had ≥20% SH (47.9% vs. 42.5%, P = 0.55). With median 19.4 months follow-up, SH was associated with worse OS per 10% increase (hazard ratio [HR] 1.12 [95% confidence interval {CI} 1.03–1.23], P = 0.009) and a ≥20% cutoff (HR 2.87 [95% CI 1.27–6.47], P = 0.01). Patients with cM0 disease and <20% SH had better 2-year OS (81.4%) compared to cM0 and ≥20% SH (44.8%) or cM1 patients who received nephrectomy (54.8%). Tumor size was also an independent predictor. Sites of distant metastasis and lines of therapy were similar for metachronous and synchronous patients. SH stratified 2-year RFS (cM0: 70.2% for <20% SH vs. 32.1% for ≥20% SH).ConclusionsSH in RCC is independently associated with OS and RFS. Patients who are cM0 with any SH may be candidates for adjuvant immunotherapy while those with ≥20% SH likely carry micrometastatic disease and should receive closer surveillance.     

Perioperative epidural analgesia is not associated with increased survival from renal cell cancer,but overall survival may be improved: a retrospective chart review

Purpose

We investigated the possible association between perioperative epidural and both cancer-specific survival (CSS) and overall survival (OS) in patients undergoing partial or radical nephrectomy for localized renal cell carcinoma (RCC).

Methods

A retrospective chart review was performed on patients who underwent complete surgical resection of localized RCC from 1994-2008 at our institution. Baseline demographics and pathological and survival data were collected. Patients with clinically or pathologically positive lymph nodes or metastatic disease at the time of surgery were excluded. Patients with pathologically positive surgical margins were also excluded. Patients were divided into two groups, systemic analgesia and epidural analgesia. Multivariable Cox regression analysis was used to determine CSS and OS, and survival curves were generated using the Kaplan-Meier method.

Results

Four hundred thirty-eight patients were included in the analysis. Baseline characteristics of both groups were similar. Median follow-up was 77 months. On multivariable analysis, patient age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), epidural status (HR, 0.5; 95% CI, 0.4 to 0.8), year of surgery (HR, 0.9; 95% CI, 0.89 to 0.95), and pathologic T-stage (pT-stage) ≥ 2 (pT-stage2: HR, 2.2; 95% CI, 1.2 to 4.1 and pT-stage3: HR, 3.1; 95% CI, 2.0 to 4.7) were independent predictors of OS. Nevertheless, epidural status did not significantly predict CSS (P = 0.73), while T-stage and year of surgery maintained their respective predictive significance. Tumour grade did not significantly affect OS or CSS.

Conclusions

Our retrospective analysis suggests that epidural at the time of surgical excision of localized RCC does not significantly impact CSS. Nevertheless, use of epidural was associated with significantly improved OS. Future prospective clinical and laboratory studies are warranted in order to characterize these associations further and determine the underlying mechanisms.

     

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.     

Prognostic impact of paraneoplastic syndromes on patients with non-metastatic renal cell carcinoma undergoing surgery: Results from Canadian Kidney Cancer information system

IntroductionThe impact of paraneoplastic syndromes (PNS) on survival in patients with renal cell carcinoma (RCC) is uncertain. This study was conducted to analyze the association of PNS with recurrence and survival of patients with non-metastatic RCC undergoing nephrectomy.MethodsThe Canadian Kidney Cancer information system is a multi-institutional cohort of patients started in January 2011. Patients with nephrectomy for non-metastatic RCC were identified. PNS included anemia, polycythemia, hypercalcemia, and weight loss. Associations between PNS and recurrence or death were assessed using Kaplan-Meier curves and multivariable analysis.ResultsOf 4337 patients, 1314 (30.3%) had evidence of one or more PNS. Patients with PNS were older, had higher comorbidity, and had more advanced clinical and pathological tumor characteristics as compared to patients without PNS (all p<0.05). Kaplan-Meier five-year estimated recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were significantly worse in patients with PNS (63.7%, 84.3%, and 79.6%, respectively, for patients with PNS vs. 73.9%, 90.8%, and 90.1%, respectively, for patients without PNS, all p<0.005). On univariable analysis, presence of PNS increased risk of recurrence (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.48–1.90, p<0.0001) and cancer-related death (HR 1.85, 95% CI 1.34–2.54, p=0.0002). Adjusting for known prognostic factors, PNS was not associated with recurrence or survival.ConclusionsIn non-metastatic RCC patients undergoing surgery, presence of PNS is associated with older age, higher Charlson comorbidity index score, advanced tumor stage, and aggressive tumor histology. Following surgery, baseline PNS is not strongly independently associated with recurrence or death.     

Association of preoperative serum De Ritis ratio with oncological outcomes in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

PurposeIdentifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.Material and methodsmRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut‐off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut‐off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis.ResultsAmong 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16–58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01–1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02–1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05–1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR.ConclusionDespite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features.     

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

BackgroundKidney 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.MethodsThe 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.ResultsNine 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.ConclusionsThere 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.     

Sarcopenia as a predictor of postoperative outcomes after urologic oncology surgery: A systematic review and meta-analysis

AimSarcopenia as a reliable prognostic predictor in urologic oncology surgery remains controversial, and no consensus amongst researchers exists regarding the management of patients with sarcopenia. This meta-analysis was conducted to investigate the association between sarcopenia and postoperative outcomes after urologic oncology surgery.MethodsA systematic search in MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library databases was conducted to identify the potential studies published before August 2019. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated through inverse variance with random or fixed effects models.ResultsSeventeen retrospective cohorts comprising 3,948 patients were included with sarcopenia prevalence between 25% and 68.9%. Patients with sarcopenia had significantly shorter overall survival (OS; HR = 2.06, 95% CI: 1.44–2.95; P < 0.001; I-square (I²) = 86%) and cancer-specific survival (HR = 2.16, 95% CI: 1.60–2.92; P < 0.001; I² = 49.4%) than those without sarcopenia. Sarcopenia was independently associated with increased all-cause mortality (HR = 1.50, 95% CI: 1.26–1.80; P < 0.001; I² = 0%) and cancer-specific mortality (HR = 1.50, 95% CI: 1.12–2.01; P = 0.006; I² = 0%). No prognostic difference was observed in the postoperative risk of total complications and systemic progression except lymphovascular invasion status.ConclusionsSarcopenia is an independent poor prognostic factor for patients undergoing urologic oncology surgery, particularly postoperative risks of short survival and increased mortality. Thus, preoperative sarcopenia evaluation can provide clinicians with important information to guide and individualise patient management and improve surgical outcomes.     

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.     

Systematic review and meta-analysis of radiation therapy for high-risk non-muscle invasive bladder cancer

INTRODUCTIONRadiation therapy (XRT) has been investigated as a possible treatment for high-risk non-muscle invasive bladder cancer (NMIBC) with the goal of bladder preservation, especially with the ongoing Bacillus Calmette-Guerin (BCG) shortage. Yet, little is known about the clinical efficacy and the quality of evidence supporting XRT for NMIBC. Herein, we performed a systematic review and meta-analysis to evaluate XRT in the treatment of patients with high-risk NMIBC.METHODSCochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were searched for high-risk NMIBC (high grade T1, T1/Ta with associated risk features: carcinoma in-situ (CIS), multifocality, > 5cm in diameter, and/or multiple recurrences) treated with primary XRT. Outcomes evaluated were recurrence-free survival (RFS), cancer-specific-survival (CSS), overall survival (OS), and salvage cystectomy and progression to metastatic disease rates. A meta-analysis was performed to assess outcomes for XRT in NMIBC.RESULTSOverall,13 studies including 746 patients met the search criteria. The 5-year rates of RFS, CSS and OS were 54% (95% CI = 38% – 70%), 86% (95% CI = 80% – 92%), and 72% (95% CI = 64% – 79%). Notably, 13% of patients proceeded to salvage radical cystectomy and 9% developed metastatic disease. All studies were of poor quality, comprising single institution and retrospective studies with only one clinical trial.CONCLUSIONXRT for high-risk NMIBC provides some degree of oncologic control, although distant progression was noted. In the setting of the low-quality evidence, a prospective clinical trial is needed to clearly define the risks and benefits of this approach.     

Whether histologic subtyping affect the oncological outcomes of patients with papillary renal cell carcinoma: evidence from a systematic review and meta-analysis

BackgroundWhether the histologic subtype (type 1 and type 2) of papillary renal cell carcinoma (pRCC) is a tool to predict the prognosis is of great debate. This study is aimed to evaluate the prognostic significance of histologic subtype in patients with pRCC after surgery through a systematic review and meta-analysis.MethodsWe searched PubMed, the Web of Science, Cochrane library and EMBASE databases to identify studies published until January 20, 2021 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were deemed eligible if they compared the overall survival (OS), cancer specific survival (CSS), recurrence-free survival (RFS) or disease-free survival (DFS) between patients with type 1 or type 2 pRCC. And the corresponding hazard ratios (HRs) and 95% conference intervals (CIs) were collected for meta-analysis and further subgroup analysis.ResultsOverall 22 studies with a total of 4,494 patients were considered eligible and included for the systematic review and meta-analysis. The pooled results showed that type 2 pRCC was associated with a worse OS (pooled HR 1.61, 95% CI: 1.10–2.36, P=0.02) and CSS (pooled HR 1.59, 95% CI: 1.00–2.51, P=0.05). However, the subgroup analysis yielded the same result as the initial analysis only when the HRs were extracted from univariate analysis. In studies with multivariate analysis, type 2 pRCC was not statistically associated with a worse OS (pooled HR 1.22, 95% CI: 0.97–1.53, P=0.27), CSS (pooled HR 1.16, 95% CI: 0.67–2.00, P=0.60), and DFS (pooled HR 1.33, 95% CI: 0.93–1.91, P=0.12) compared to type 1 pRCC.DiscussionHistologic subtype is not an independent prognostic factor for patients with pRCC, although the result needs to be taken with caution. And studies with retrospective study design, larger sample size and longer follow-up period are required to verify these results.     

Leibovich score is the optimal clinico-pathological system associated with recurrence of non-metastatic clear cell renal cell carcinoma

PurposeTo determine the optimal post-operative risk stratification system associated with survival following surgery for clear cell renal cell carcinoma (ccRCC): tumour grade, tumour stage, Leibovich 2003, Leibovich 2018, Kattan, Stage, size, grade and necrosis (SSIGN) or UCLA Integrated Staging System (UISS) scores.Methods542 patients with non-metastatic ccRCC who underwent nephrectomy 2008?2018 were reviewed. Primary outcome was recurrence-free survival (RFS), with secondary outcomes cancer-specific survival (CSS) and overall survival (OS).ResultsAll systems were significantly associated with RFS, CSS and OS by Kaplan-Meier and unadjusted Cox-regression. ROC analysis identified that Leibovich 2003, Leibovich 2018A or B and SSIGN were optimally association with 5year RFS (AUC (Area under curve) 0.87, 0.86, 0.86 and 0.86), but Leibovich 2003 or 2018A offered additional information on adjusted regression analysis (HR 1.24, P = 0.02; HR 1.17, P = 0.04). ROC analysis identified that Leibovich 2018B, Leibovich 2003, SSIGN and UISS were equally associated with 5 year OS (AUC 0.76, 0.74, 0.73 and 0.72). UISS added additional explanation of the variance in OS on adjusted regression analysis (HR 1.96, P = 0.002). A novel combination of Leibovich 2003 score and Eastern Co-operative Oncology Group (ECOG) performance status improved 5 year OS association compared to the Leibovich 2003 alone (AUC 0.78, P = 0.001), without affecting association with 5year RFS (AUC 0.87, P = 0.75).ConclusionsAll systems were robust tools associated with RFS, CSS and OS in ccRCC. In our cohort, the Leibovich 2003 and Leibovich 2018A scores may be better associated with RFS compared to other strategies. The UISS, Leibovich 2018B or Leibovich 2003 combined with ECOG performance status may stratify OS better than other modalities.     

Tumor diameter response in patients with metastatic clear cell renal cell carcinoma is associated with overall survival

ObjectiveTumor shrinkage of at least 10% after presurgical targeted molecular therapy (TMT) in renal cell carcinoma (RCC) patients has been associated with better overall survival (OS) outcomes. We characterized primary and metastatic tumor diameter response and OS in patients with metastatic clear cell RCC (ccRCC) who received preoperative TMT, immunotherapy, or both followed by deferred cytoreductive nephrectomy (dCN).Materials and MethodsPatients with metastatic ccRCC (n = 198) who underwent preoperative therapy and dCN from 2005 to 2019 were identified retrospectively. Longest primary and metastatic tumor diameters were calculated using cross-sectional images obtained before systemic therapy and dCN using the Response Evaluation Criteria in Solid Tumors. Patients were stratified by tumor shrinkage of at least 10% in the primary and/or metastatic tumors after systemic therapy. The Kaplan-Meier method was used to estimate OS, and Cox proportional hazards models were used to assess the association of patient characteristics with OS.ResultsIn total, 31.31% of patients had only metastatic tumor shrinkage (MTS) ≥ 10%, 8.08% had only primary tumor shrinkage (PTS) ≥ 10%, 32.32% had PTS and MTS ≥ 10%, and 28.28% had PTS/MTS < 10%. The median OS, number of patients with tumor shrinkage ≥ 10%, and International Metastatic Database Consortium (IMDC) scores were similar among the 3 systemic therapy groups (all P ≥ 0.80). Patients with MTS ≥ 10%, PTS ≥ 10%, and PTS/MTS ≥ 10% had significantly longer median OS compared to patients with PTS/MTS < 10% (P < 0.01). Patients with intermediate-risk IMDC scores had significantly longer median OS compared to patients in the poor-risk group. After adjusting for preoperative therapy and IMDC risk group, MTS ≥ 10%, PTS ≥ 10%, and PTS/MTS ≥ 10% were associated with better OS outcomes (HR 0.48 95% CI 0.32–0.73, P < 0.001; HR 0.48, 95% CI 0.23–0.98, P = 0.04; HR 0.44, 95% CI 0.29–0.67, P < 0.001, respectively).ConclusionsIntermediate risk score and shrinkage of at least 10% in the primary tumor, metastases, or both were associated with better OS outcomes in patients with metastatic ccRCC who underwent dCN independent of the type of preoperative systemic therapy.