Multicenter Analysis of Postoperative Complications in Octogenarians After Radical Cystectomy and Ureterocutaneostomy: The Role of the Frailty Index.

BACKGROUND: The purpose of this study was to assess patient frailty as a risk factor for radical cystectomy (RC) complications. MATERIALS AND METHODS: We performed an analysis of prospectively collected data of consecutive patients 80 years of age or older who underwent RC and ureterocutaneostomy in 6 primary care European urology centers. Frailty was measured using a simplified frailty index (sFI) with a 5-item score including: (1) diabetes mellitus; (2) functional status; (3) chronic obstructive pulmonary disease; (4) congestive cardiac failure; and (5) hypertension, with a maximum 5-item score meaning high level of frailty. Within 90 days surgical complications were scored according to the Clavien Classification System (CCS). sFI ≥3 was considered as poor frailty status. Clinical and pathological variables were analyzed as predictors of severe complications (CCS ≥3). RESULTS: One hundred seventeen patients were enrolled. Most patients reported an sFI score of 2 and 3, respectively, 31/117 (26.5%) and 45/117 patients (38.5%). CCS ≥3 occurred in 17/117 patients (14.5%). Patients with sFI ≥3 were significantly older than patients with sFI <3 (median age, 85 years [interquartile range (IQR), 82-86] versus 82 years [IQR, 80-84]; P = .001). Most CCS ≥3 scores occurred in patients with sFI ≥3: 13 (11.1%) versus 4 (3.4%; P = .02). No significative differences were detected in terms of length of hospital stay, pathological stage, and postoperative bowel canalization when related to sFI. sFI ≥3 was an independent risk factor of CCS ≥3 in univariate and multivariate analysis (respectively, odds ratio [OR], 3.81 [95% confidence interval (CI), 1.16-12.5; P = .02] and OR, 3.1 [95% CI, 0.7-13.7; P = .01]). Body mass index, age, American Society of Anesthesiologists score ≥3, and pathological stage were not related to CCS ≥3. CONCLUSION: RC appears feasible in elderly patients with an sFI <3. In cases of sFI ≥3, this choice should be carefully valued, discussed, and possibly avoided because of a higher risk of complications.

Evaluation of the prognostic significance of perirenal fat invasion and tumor size in patients with pT1-pT3a localized renal cell carcinoma in a comprehensive multicenter study of the CORONA project. Can we improve prognostic discrimination for patients with stage pT3a tumors?

BACKGROUND: The current TNM system for renal cell carcinoma (RCC) merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. In addition, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. OBJECTIVE: To analyze the prognostic significance of PFI, RVI, and tumor size in pT1-pT3a RCC. DESIGN, SETTING, AND PARTICIPANTS: Data for 7384 pT1a-pT3a RCC patients were pooled from 12 centers. Patients were grouped according to stages and PFI/RVI presence as follows: pT1-2N0M0 (n=6137; 83.1%), pT3aN0M0 + PFI (n=1036; 14%), and pT3aN0M0 (RVI ± PFI; n=211; 2.9%). INTERVENTION: Radical nephrectomy or nephron-sparing surgery (NSS) (1992-2010). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cancer-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazards regression models, as well as sensitivity and discrimination analyses, were used to evaluate the impact of clinicopathologic parameters on cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Compared to stage pT1-2, patients with stage pT3a RCC were significantly more often male (59.4% vs 53.1%) and older (64.9 vs 62.1 yr), more often had clear cell RCC (85.2% vs 77.7%), Fuhrman grade 3-4 (29.4% vs 13.4%), and tumor size >7 cm (39.1% vs 13%), and underwent NSS less often (7.5% vs 36.6%; all p<0.001). According to multivariate analysis, CSM was significantly higher for the PFI and RVI ± PFI groups compared to pT1-2 patients (hazard ratio [HR] 1.94 and 2.12, respectively; p<0.001), whereas patients with PFI only and RVI ± PFI did not differ (HR 1.17; p=0.316). Tumor size instead enhanced CSM by 7% per cm in stage pT3a (HR 1.07; p<0.001) with a 7 cm cutoff yielding the highest prediction accuracy. CONCLUSIONS: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a RCC might be justified. Enhanced prognostic discrimination of stage pT3a RCC appears to be possible by applying a tumor size cutoff of 7 cm within an alternative staging system. PATIENT SUMMARY: Prognosis prediction for patients with localized renal cell carcinoma up to stage pT3a can be enhanced by including tumor size with a cutoff of 7 cm as an additional parameter in the TNM classification system.

Results of a comparative study analyzing octogenarians with renal cell carcinoma in a competing risk analysis with patients in the seventh decade of life.

OBJECTIVES: To analyze clinicopathological features and survival of surgically treated patients with renal cell carcinoma (RCC) ≥ 80 years of age in comparison with patients between the ages of 60 and 70 years. MATERIALS AND METHODS: The data for 2,516 patients with a median follow-up of 57 months were retrieved from a multinational database (Collaborative Research on Renal Neoplasms Association [CORONA]), including data for 6,234 consecutive patients with RCC after radical or partial nephrectomy. Comparative analysis of clinicopathological features of 241 octogenarians (3.9% of the database) and 2,275 reference patients between the ages of 60 and 70 years (36.5%) was performed. Multivariable regression analysis adjusted for competing risks was applied to identify the effect of advanced age on cancer-specific mortality (CSM) and other-cause mortality (OCM). Furthermore, instrumental variable analysis was employed to reduce residual confounding by unmeasured parameters. RESULTS: Significantly more women were present (50% vs. 40%, P = 0.004), and significantly less often nephron-sparing surgery was performed in octogenarians compared with the reference group (11% vs. 20%, P<0.001). Although median tumor size and stages did not significantly defer, older patients less often had advanced or metastatic disease (N+/M1) (4.6% vs. 9.6%, P = 0.009). On multivariable analysis, higher CSM (hazard ratio = 1.48, P = 0.042) and OCM rates (hazard ratio = 4.32, P<0.001) were detectable in octogenarians (c-indices = 0.85 and 0.72, respectively). Integration of the variable age group in multivariable models significantly increased the predictive accuracy regarding OCM (6%, P<0.001), but not for CSM. Limitations are based on the retrospective study design. CONCLUSIONS: Octogenarian patients with RCC significantly differ in clinical features and display significantly higher CSM and OCM rates in comparison with their younger counterparts.

Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.

PURPOSE: We analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old. MATERIALS AND METHODS: Overall 2,572 patients retrieved from a multicenter international database comprised of 6,234 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.8%) were compared to those of 2,275 patients (36.5%) 60 to 70 years old, who served as the reference group. Median followup was 59 months. The impact of young age and further parameters on disease specific mortality and all cause mortality was evaluated by multivariate Cox proportional hazards regression analyses. RESULTS: Young patients more frequently underwent nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p = 0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more frequent in young patients. On multivariate analysis older patients had a higher disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001). The c indices for the Cox models were 0.87 and 0.78, respectively. However, integration of the variable age group did not significantly increase the predictive accuracy of the disease specific and all cause mortality models. CONCLUSIONS: Young patients with renal cell carcinoma (40 years old or younger) have significantly different frequencies of clinical and histopathological features, and a significantly lower all cause and disease specific mortality compared to patients 60 to 70 years old.

Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database.

PURPOSE: To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery. METHODS: A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30-106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868-0.870, p = 0.628) and OS (0.775-0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS. CONCLUSIONS: This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.

Assessing the accuracy and generalizability of the preoperative and postoperative Karakiewicz nomograms for renal cell carcinoma: results from a multicentre European and US study.

OBJECTIVE: To assess the accuracy and generalizability of the pre- and postoperative Karakiewicz nomograms for predicting cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: This retrospective study included 3231 patients from European and US centres, who were treated by radical or partial nephrectomy for RCC between 1992 and 2010. Prognostic scores for each patient were calculated and the primary endpoint was CSS. Discriminating ability was assessed by Harrell's c-index for censored data. The 'validation by calibration' method proposed by Van Houwelingen was used for checking the calibration of covariate effects. Calibration was graphically explored. RESULTS: Local and systemic symptoms were present in 23.2% and 9.1% of the patients, respectively. The median follow-up (FU) was 49 months. At the last FU, 408 cancer-related deaths were recorded, Kaplan-Meier estimates of CSS (with 95% confidence intervals [CIs]) at 5 and 10 years were 0.86 (0.84-0.87) and 0.77 (0.75-0.80), respectively. Both nomograms discriminated well. Stratified c-indices for CSS were 0.784 (95% CI 0.753-0.814) for the preoperative nomogram, and 0.842 (95% CI 0.816-0.867) for the postoperative one, with a significant difference between the two values (P < 0.001). The covariate-based predictions on our data for both nomograms were valid. The calibration plots showed no relevant departures from ideal predictions. CONCLUSIONS: The results suggest that the postoperative Karakiewicz nomogram discriminates substantially better than the preoperative one. These nomogram-based predictions may be used as benchmark data for pretreatment and postoperative decision-making in patients at various stages of RCC.

[Oncological outcomes of laparoscopic and open treatment (nephroureterectomy) for urothelial tumors of the upper urinary tract]. / Risultati oncologici del trattamento open e laparoscopico (nefroureterectomia) per i tumori uroteliali dell'alta via escretrice.

Currently, the treatment of choice in urothelial tumors of the upper urinary tract is nephroureterectomy (NU) as an Open procedure (ONU), though the laparoscopic treatment is now routinely performed as a minimally invasive therapy (LNU). LNU has demonstrated oncologic safety at least equivalent to open, but some issues dealing with cancer still remain. We retrospectively analyzed data from 36 LNU performed between 2006 and 2010, compared with data of 32 ONU performed in 2002-2005 (pre-laparoscopy era). The mean follow-up was 23 months in patients undergoing LNU and 42 months for those treated with ONU. In particular, we evaluated cancer recurrence, the site of recurrence and survival rates. We had local recurrence in 3 patients (8.3%) after LNU and 2 after ONU (6.25%). 2 patients who underwent LNU (5.5%) died of metastatic disease at 9 and 12 months; 3 patients who underwent ONU (9.3%) died of metastasis at 12, 16 and 23 months, respectively. Bladder recurrence was observed in 3 patients after ONU and in 4 after LNU. The most frequent sites of cancer recurrence were: local recurrence (3 LUN, 2 ONU), 1 laparoscopic port recurrence, 3 regional lymph node recurrences (2 LNU, 1ONU), bladder recurrences (3 LNU, 4 ONU). There were no significant differences in disease recurrence and even survival rates at 1 and 3 years were not very different between the two techniques. The grade and stage of cancer affecting the incidence of metastatic disease, as well as the localization of early disease (pelvis-ureter-both) is a negative prognostic factor, rather than the surgical technique used. Therefore, there is no evidence that the control is compromised in cancer patients treated with LNU rather than with ONU.