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.

Laparoendoscopic single-site (LESS) adrenalectomy and partial nephrectomy: current Italian experience with two challenging surgical procedures.

Since its initial clinical use in urology, there has been an increasing enthusiasm and a growing interest for laparoendoscopic single-site surgery (LESS). Several clinical series have been reported with an estimated cumulative clinical experience of more than four hundred so far. Nowadays, virtually all extirpative and reconstructive urological procedures have been described and shown to be feasible and safe, including advanced reconstructive procedures and major extirpative ones. Among them, adrenalectomy and partial nephrectomy represent highly complex procedures. Initial clinical data have been recently reported to test the safety and efficacy of these interventions in selected patients. Herein, we describe our initial cases of unclamp LESS partial nephrectomy and adrenalectomy. In our opinion, LESS is an established technique within the field of minimally invasive surgery. Even if further studies are needed to demonstrate its actual benefits, early clinical outcomes are encouraging and LESS might represent the way to go in minimally invasive urological surgery.

A 1-year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the efficacy of 1-year maintenance after a 6-week cycle of early intravesical chemotherapy, as the role of maintenance in intravesical chemotherapy is debated. PATIENTS AND METHODS: Between May 2002 and August 2003, 577 patients with non-muscle-invasive bladder cancer (NMI-BC) underwent transurethral resection (TUR) and early intravesical chemotherapy (epirubicin, 80 mg/50 mL). They were randomized between a 6-week induction cycle and the induction cycle plus maintenance with 10 monthly instillations. In all, 95 patients with T1G3, Tis or single and primary Ta-T1 G1-G2 tumours were excluded; 482 patients at intermediate risk of recurrence continued the study. All patients had cytology and cystoscopy at 3-monthly intervals for the first 2-years and 6-monthly thereafter. RESULTS: The tumours' characteristics were equally distributed between the two arms. Treatment interruption for toxicity was required in 39 patients. One death due to toxicity of early instillation occurred. The median follow-up was 48 months. Ten patients (2.5%) progressed and 117 patients (29.6%) recurred. No statistically significant difference in the recurrence-free rate (RFS) was detected between the two arms (P = 0.43). An advantage in favour of the maintenance arm was evident only at 18 months after TUR (P = 0.03). A trend for a higher benefit from maintenance in primary and multiple tumours was detected. CONCLUSIONS: In patients with intermediate risk NMI-BC treated by TUR and early adjuvant chemotherapy, adding a maintenance regimen with monthly instillations for 1 year is of limited efficacy in preventing recurrence.

Thromboprophylaxis in radical retropubic prostatectomy: efficacy and patient compliance of a dual modality.

OBJECTIVES: The risk of developing venous thromboembolism (VTE) in urologic patients undergoing major surgery without thromboprophylaxis is high (up to 40%). The aims were to study the acceptability rate of and overall patient satisfaction with an automatic sequential leg compression system and the short-term effectiveness of a combined VTE prevention modality. METHODS: One-hundred and eighty-four consecutive patients undergoing radical retropubic prostatectomy were postoperatively treated with enoxaparine and intermittent pneumatic compression of the thigh. By completing a questionnaire, the patients were prospectively studied to evaluate the comfort and tolerability of a compression device (SCD Response Compression System; Covidien, Gosport, UK). The patients were monitored for complications and development of VTE for up to 4 weeks postoperatively. The device used ensures customized and effective compression therapy matching the patient's individual vascular refill by sequential, gradient, circumferential microprocessor-controlled compression cycles. RESULTS: No clinically evident VTE, critical bleeding or postoperative death occurred during the study period. Drain output was associated with transfusion requirement (p < 0.001), obesity (p < 0.02) and longer operation duration (p < 0.001). The sequential compression devices were well tolerated by 63% of the patients, in that the sleeves were judged as being pleasant (72%) and nonoppressive (79%). Patients reported bothersome insomnia (23%) and noise (44%), and early removal was required in 3%. CONCLUSIONS: Combined mechanical and pharmacological thromboprophylaxis was highly effective, well tolerated, and safe. The device tested showed a high comfort and tolerability profile. The use of combined modalities for VTE prophylaxis is justified in patients at very high risk of VTE, such as those undergoing radical retropubic prostatectomy.

Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study.

BACKGROUND: The objective of the current study was to compare, in a large multicenter study, the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC). METHODS: A total of 2404 records of patients from 6 European centers were retrospectively reviewed. For each patient, prognostic scores were calculated according to four models: the Kattan model, the University of California at Los Angeles integrated staging system (UISS) model, the Yaycioglu model, and the Cindolo model. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Discriminating ability was assessed by the Harrell c-index for censored data. The primary end point was overall survival (OS), and the secondary end points were cancer-specific survival (CSS) and disease recurrence-free survival (RFS). RESULTS: At last follow-up, 541 subjects had died of any causes, with a 5-year OS rate of 80%. The 5-year CSS and RFS rates were 85% and 78%, respectively. All models discriminated well (P < 0.0001). The c-indexes for OS were 0.706 for the Kattan nomogram, 0.683 for the UISS model, and 0.589 and 0.615 for the Yaycioglu and Cindolo models, respectively. The Kattan nomogram was found to improve discrimination substantially in the UISS intermediate-risk patients. CONCLUSIONS: The current study appears to better define the general applicability of prognostic models for predicting survival in patients with nonmetastatic RCC treated with nephrectomy. The results suggest that postoperative models discriminate substantially better than preoperative ones. The Kattan model was consistently found to be the most accurate, although the UISS model was only slightly less well performing. The Kattan model can be useful in the UISS intermediate-risk patients.

Chromophobe renal cell carcinoma: comprehensive analysis of 104 cases from multicenter European database.

OBJECTIVES: To analyze the clinical behavior of chromophobe renal cell carcinoma (CRCC), we retrospectively evaluated the data from six European centers. In 1985, CRCC was identified as a new RCC histologic subtype. Because of its low frequency, only few large CRCC series are available. METHODS: We created a renal cancer database including 3228 patients who underwent surgery between 1986 and 2002 in six European centers. The relevant clinical and pathologic data were extracted from the clinical charts at each institution and collected into a unique database. RESULTS: Of the 3228 patients, 104 (3.2%) affected by CRCC were identified. The mean age at diagnosis was 57.6 years (range 22 to 83). Of the 104 patients, 51 (49%) were men and 53 (51%) were women. The mean tumor size was 6.4 +/- 3.6 cm. An incidental diagnosis accounted for 61.5% of the cases. Radical nephrectomy was performed in 88 patients (85%). After a median follow-up of 38 months (mean 44, range 1 to 153), no local recurrence was observed. The 5-year overall survival rate for CRCC was 81%. Of the 104 patients, 5 (4.8%) and 9 (8.6%) died of unrelated causes and renal cancer, respectively. CONCLUSIONS: Our series confirmed a favorable outcome for the CRCC subtype with little local aggressiveness and a low propensity for progression and death from cancer.

Standard versus hydrophilic catheterization in the adjuvant treatment of patients with superficial bladder cancer.

INTRODUCTION: The aim of the present study is to compare a hydrophilic catheter to the standard polyvinyl chloride catheter with regard to bacteriological safety and overall comfort in patients undergoing intravesical immuno- or chemotherapy for bladder cancer. MATERIALS AND METHODS: One hundred patients (80 males, 20 females; median age 65.8 years, range 48-79 years) eligible for intravesical prophylaxis of superficial bladder cancer recurrences were randomized to receive intravesical therapy using a standard catheter (group A, n = 50) or a hydrophilic catheter (group B, n = 50). Urinalysis and urine culture were performed 2 days after catheterization. Comfort during catheterization was assessed by a 5-point visual analogue scale at the end of the first four instillations. RESULTS: Urinary tract infection (UTI) was detected in 7.4% of catheterizations in group A, whereas it occurred in 3.5% of catheterizations in group B (p < 0.01). Escherichia coli was the most frequent pathogen regardless of the device used. At the end of each of the first four instillations, the mean score for discomfort was significantly higher in group A than in group B (p < 0.001), although catheterization was progressively better tolerated regardless of the device used (both p < 0.005). None of the patients were found to be suffering from orchitis, epididymitis or gross haematuria. CONCLUSION: Hydrophilic catheters may be used safely and are well tolerated by patients undergoing intravesical immuno- or chemotherapy. The hydrophilic catheter was associated with a significantly lower occurrence of UTI and higher acceptability compared to the standard device. These data should be considered with regard to patient compliance with intravesical therapy.