Comparison of post-operative intravesical recurrence and oncological outcomes after open versus laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma

Object

To retrospectively evaluate intravesical recurrence and oncological outcomes after open or laparoscopic radical nephroureterectomy (RNU) for the upper urinary tract urothelial carcinoma (UUT-UC).

Patients and methods

This study comprised 122 patients diagnosed UUT-UC and subsequently nephroureterectomy was performed on. Several clinical and pathological parameters were emphasized for comparison of clinical outcomes.

Results

Among 122 patients with UUT-UC, 101 (82.8 %) and 21 (17.2 %) underwent open or laparoscopic radical nephroureterectomy (ONU or LNU), respectively. In univariable and multivariable Cox regression models, the surgical procedure exerted an impact neither on post-operative intravesical recurrence rate (p = 0.179 and 0.213, respectively) nor on cancer-specific mortality rate (p = 0.561 and 0.159, respectively). The 1-, 2- and 5-year cancer-specific survival (CSS) rates of patients undergoing ONU or LNU were 92.1 versus 95.2 %, 87.1 versus 90.5 %, 79.2 versus 85.7 %, respectively, and the Kaplan–Meier plot illustrated that patients from two groups enjoyed an equivalent survival rate (p = 0.559). Moreover, we added that previous history of bladder tumor and pre-operative hydronephrosis was associated with intravesical recurrence, whereas three prognostic factors, including pathological tumor stage, grade, and lymphovascular invasion, showed possibility to be predictors of cancer-specific mortality.

Conclusion

There existed no significant difference of intravesical recurrence and CSS between patients after ONU and LNU. Conclusively, laparoscopic radical nephroureterectomy did not present superiority to open management for patients with UUT-UC.     

Intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinomas: predictors and impact on subsequent oncological outcomes from a national multicenter study

Objectives

To identify predictive factors and assess the impact on oncological outcomes of intravesical recurrence after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC).

Methods

Using a national multicentric retrospective dataset, we identified all patients with UTUC who underwent a RNU between 1995 and 2010 (n = 482). Intravesical recurrence was tested as a prognostic factor for survival through univariable and multivariable Cox regression analysis.

Results

Overall, intravesical recurrence occurred in 169 patients (35 %) with a median age of 69.2 years (IQR: 60–76) and after a median follow-up of 39.5 months (IQR: 25–60). Actuarial intravesical recurrence-free survival estimates at 2 and 5 years after RNU were 72 and 45 %, respectively. On univariable analyses, previous history of bladder tumor, tumor multifocality, laparoscopic approach, pathological T-stage, presence of concomitant CIS and lymphovascular invasion were all associated with intravesical recurrence. On multivariable analysis, previous history of bladder cancer, tumor multifocality and laparoscopic approach remained independent predictors of intravesical recurrence. Existence of intravesical recurrence was not correlated with worst oncological outcomes in terms of disease recurrence (p = 0.075) and cancer-specific mortality (p = 0.06).

Conclusions

In the current study, intravesical recurrence occurred in 35 % of patients with UTUC after RNU. Previous history of bladder cancer, tumor multifocality, concomitant CIS and laparoscopic approach were independent predictors of intravesical recurrence. These findings are in line with recent published data and should be considered carefully to provide a definitive surveillance protocol regarding management of urothelial carcinomas regardless of the location of urothelial carcinomas in the whole urinary tract.     

The method of bladder cuff excision during laparoscopic radical nephroureterectomy does not affect oncologic outcomes in upper tract urothelial carcinoma

Purpose

To determine whether the method of bladder cuff excision (BCE) during laparoscopic radical nephroureterectomy for upper urinary tract urothelial carcinoma is associated with rates of disease recurrence or metastases.

Methods

We performed a retrospective review of all laparoscopic radical nephroureterectomies performed at our institution over 10 years. Three methods of BCE were used: transurethral incision (TUI) with Collins knife and a single intravesical port, open extravesical, and open intravesical via cystotomy. Logistic regression analyses were performed to determine whether BCE method was associated with recurrence or metastases.

Results

Laparoscopic radical nephroureterectomy was performed in 110 patients. BCE was performed via TUI in 61 patients, open extravesical in 29, and open intravesical in 20. After a median follow-up of 22 months, 36 patients (32.7 %) developed recurrences. Metastases were observed in 18 patients (16.4 %). Recurrence rates were 32.8, 27.6, and 40.0 % in the TUI, extravesical, and intravesical groups, respectively (p = 0.69). Positive surgical margins occurred in nine patients with no significant difference between groups. Factors associated with recurrence or metastases in a multivariate regression analysis were stage, positive surgical margins and carcinoma in situ (CIS). The method of BCE was not associated with oncologic outcomes.

Conclusions

The three methods of bladder cuff excision (TUI, extravesical, and intravesical) are oncologically valid with similar recurrence and metastases rates when performed during laparoscopic radical nephroureterectomy. Stage, positive margin status and CIS are predictive of adverse oncologic outcomes and can facilitate postoperative prognostication.     

Female gender is associated with higher risk of disease recurrence in patients with primary T1 high-grade urothelial carcinoma of the bladder

Purpose

An increasing body of evidence suggests gender differences in the presentation and prognosis of bladder cancer. We aimed to assess the impact of gender on outcomes in patients with primary T1 high-grade (HG) urothelial carcinoma of the bladder (UCB).

Methods

We retrospectively analysed the data from 916 patients with primary T1HG UCB from 7 tertiary care centres. Patients were treated with transurethral resection of the bladder with or without intravesical instillation therapy (IVT). Univariable and multivariable Cox regression analyses assessed the effect of gender on outcomes.

Results

Within a median follow-up of 42.8 months, 365 (39.8 %) patients experienced disease recurrence, 104 (11.4 %) progression, 59 (6.4 %) cancer-specific mortality and 190 (20.7 %) mortality of any cause. Overall, 634 (69.2 %) patients received IVT of which 234 (25.5 %) received BCG therapy. Female gender (n = 190, 20.7 %) was associated with higher risk of disease recurrence (HR:1.359;1.071–1.724, p = 0.012) in all patients and in a subgroup of patients treated with BCG therapy (HR:1.717;1.101–2.677, p = 0.017). There was no difference between genders with regard to disease progression, cancer-specific mortality and any-cause mortality. In multivariable analyses that adjusted for the effects of concomitant carcinoma in situ (CIS), tumour size, number of tumours, and IVT, gender remained an independent predictor for disease recurrence (p = 0.026) when analysed in all patients, but not in the subgroup of BCG treated patients (p = 0.093).

Conclusions

In patients with T1HG UCB, female gender is associated with higher risk of disease recurrence, but not with disease progression. This gender disparity may be due to differences in care and/or biology of UCB.     

Preoperative prognostic factors after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

Purpose

To evaluate the clinical significance of preoperative biomarkers such as laboratory data, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and clinicopathological factors in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma.

Methods

Between 1995 and 2011, a total of 99 patients treated at our institution for upper urinary tract urothelial carcinoma were enrolled in this study. The prognostic significance of various preoperative data and clinicopathological factors were analyzed. Univariate and multivariate analyses were performed using the Kaplan–Meier method with the log-rank test and a Cox proportional hazards regression model.

Results

Median patient age was 73 years (range 44–86 years), and the median follow-up period after radical nephroureterectomy was 37.9 months (range 6.6–171.4 months). The 5-year intravesical recurrence-free survival and cancer-specific survival estimates were 47.1 and 70.0 %, respectively. On multivariate analysis, concomitant bladder carcinoma was an independent predictor of intravesical recurrence (hazard ratio 3.689; P = 0.002), and infiltration (hazard ratio 14.842; P = 0.002), preoperative serum creatinine level (hazard ratio 9.992; P = 0.005), preoperative serum hemoglobin level (hazard ratio 6.370; P = 0.018) and ECOG PS (hazard ratio 4.326; P = 0.037) were associated with worse cancer-specific survival. This study is limited by biases associated with its retrospective design.

Conclusions

This study indicates that not only clinicopathological factors, but also preoperative biomarkers, such as serum creatinine and hemoglobin levels and ECOG PS, predict a poor survival in patients with upper urinary tract urothelial carcinoma.     

Gender-specific survival following radical cystectomy for pT4 bladder cancer

Purpose

To evaluate the association of gender with survival following radical cystectomy (RC) for patients with pT4 bladder cancer.

Materials and methods

We reviewed our institutional registry of 2,088 patients treated with RC between 1980 and 2005 to identify 128 with pT4 tumors, including 91 males and 37 females. Survival was estimated using the Kaplan–Meier method and compared with log-rank test. Cox hazard regression models were used to analyze the association of clinicopathologic demographics, including gender, with outcome.

Results

A total of 7 women and 30 men with pT4 tumor received perioperative chemotherapy. Median postoperative follow-up was 10.5 years, during which time 27 patients experienced local recurrence (LR) and 120 died, including 90 who died from bladder cancer. Women with pT4 tumor trended to have higher 5-year LR-free survival (72 vs. 59 %; p = 0.83), cancer-specific survival (31 vs. 17 %; p = 0.50), and overall survival (19 vs. 11 %; p = 0.33), although these differences did not reach statistical significance. On multivariate analysis, moreover, gender was not significantly associated with LR (HR 0.96; p = 0.93), cancer-specific mortality (HR 1.05; p = 0.87), or all-cause mortality (ACM) (HR 1.14; p = 0.58). Instead, poor ECOG performance status and pN+ disease were associated with an increased risk of ACM, while removal of a greater number of lymph nodes was associated with decreased ACM.

Conclusion

We did not find gender-specific disparities in survival following RC for pT4 bladder cancer. Prognosis was instead driven by patient performance status and lymph node status.     

The impact of smoking on pathologic response to neoadjuvant cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer

Purpose

Smoking is the primary etiologic risk factor for bladder cancer and has been implicated in mechanisms of chemoresistance. We investigated smoking as a potential predictor for pathologic outcomes after neoadjuvant chemotherapy (NC) and radical cystectomy (RC) for muscle-invasive bladder cancer.

Methods

We identified 139 patients treated with neoadjuvant cisplatin-based chemotherapy followed by RC for T2-4aN0M0 bladder cancer. Logistic regression was used to evaluate associations between smoking characteristics and pathologic outcomes (pT0, complete response; pT0/pTis/pT1, any response). In a secondary analysis, multivariate Cox regression was used to assess associations between smoking and recurrence-free and cancer-specific survival.

Results

Our cohort consisted of 99 (71 %) males, with a median age of 65 (interquartile range 56, 71). Prevalence of never, former, and current smokers was 25, 45, and 29 %, respectively. In total, 63 patients experienced disease recurrence, 39 died of disease, and 11 died of other causes. There were no statistically significant associations between smoking characteristics and complete (p = 0.5) or any (p = 0.2) pathologic response to NC. Similarly, we did not find any association between smoking characteristics and recurrence (p = 0.6) or cancer-specific survival (p = 0.9).

Conclusions

In this series, smoking characteristics were not found to be predictive of pathologic response after NC and RC, although this analysis was limited by the small study sample size. However, the harmful effects of smoking warrants continued emphasis on smoking cessation counseling in bladder cancer patients.     

A Multi-Institutional Validation of the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio for Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Background

To externally validate the prognostic impact of preoperative neutrophil–lymphocyte ratio (pre-NLR) in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU).

Methods

A total of 665 patients from 12 institutions were included. The median follow-up was 28 months. Associations between pre-NLR level and outcome were assessed using multivariate analysis. A pre-NLR level of >3.0 was defined as elevated.

Results

Pre-NLR levels were elevated in 184 patients (27.7 %), and pre-NLR elevation was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive lymphovascular invasion (LVI), and lymph node involvement in RNU specimens. The 5-year recurrence-free and cancer-specific survival rates were 57.0 % (p < 0.001) and 60.2 % (p < 0.001), respectively, in patients with elevated pre-NLR, and 69.2 and 77.3 %, respectively, in their counterparts. Multivariate analysis showed that elevated pre-NLR was an independent risk factor for predicting subsequent disease recurrence (p = 0.037; hazard ratio (HR) 1.38) and cancer-specific mortality (p = 0.036;, HR 1.47), although the addition of pre-NLR slightly improved the accuracies of the base model for predicting both disease recurrence and cancer-specific mortality to 79.8 % (p = 0.041) and 83.0 % (p = 0.039), respectively (gain in predictive accuracy: 0.2 and 0.1 %, respectively).

Conclusion

This multi-institutional study revealed that elevated pre-NLR was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive LVI, and lymph node involvement in RNU specimens, and elevated pre-NLR was an independent risk factor of disease recurrence and cancer-specific mortality in UTUC patients treated with RNU.     

Segmental ureterectomy does not compromise the oncologic outcome compared with nephroureterectomy for pure ureter cancer

Purpose

Pure ureter cancers are rare and account for only 1–3 % of urothelial carcinomas with limited data. Nowadays, nephron-sparing methods are reserved mainly for imperative cases. This study intends to assess the oncologic outcome between segmental ureterectomy (SU) and radical nephroureterectomy (RNU) for pure ureteral urothelial carcinoma.

Methods

From July 2004 to August 2010, 112 patients at a single tertiary referral center were included. Perioperative data were obtained from our institutional database. Postoperative CT scan, cystoscopy, and contralateral renal echo were performed regularly for survey of disease recurrence.

Results

The mean length of follow-up was 43.8 and 48.3 months for the RNU and SU group, respectively. The bladder recurrences, local recurrences, distant metastasis, and cancer-specific survival rates showed no significant differences between RNU and SU (36.4 vs. 34.2 %, p = 0.83; 23.4 vs. 14.3 %, p = 0.27; and 16.9 vs. 8.6 %, p = 0.244, and 13.0 vs. 5.7 %, p = 0.249, respectively).

Conclusion

The study suggested that SU is not inferior to RNU for ureter cancer in oncologic outcomes and is less invasive and better nephron preservation.     

Independent Predictors for Bladder Outcomes after Treatment of Intravesical Recurrence following Radical Nephroureterectomy in Patients with Primary Upper Tract Urothelial Carcinoma

Background

Few studies have described the clinical courses and outcomes in the bladder after treatment of intravesical recurrence after radical nephroureterectomy (RNU) in patients with primary upper tract urothelial carcinoma (UTUC). We investigated the indicators for predicting subsequent bladder outcomes after treatment of intravesical recurrence after RNU.

Methods

A total of 241 patients with primary UTUC (pTa-4N0M0) who experienced intravesical recurrence after RNU were included. Of these patients, 101 (41.9 %) underwent Bacillus Calmette-Guérin treatments, whereas 49 (20.3 %) underwent intravesical chemotherapy. The median follow-up period after initial transurethral resection of the bladder tumor was 33 months. Relationships with bladder outcomes were analyzed by using multivariable analysis.

Results

Ninety-six patients experienced intravesical recurrence, and bladder progression was observed in 13. Cumulative incidence rates of intravesical recurrence at 1 and 5 years after treatment of the first intravesical recurrence were 31.0 and 48.4 %, whereas those of bladder progression at 1 and 5 years thereafter were 2.4 and 8.0 %. Multivariate analysis showed that the number of recurrent tumors and pT1 tumors at the time of the first intravesical relapse were independent risk factors for subsequent intravesical recurrence. With respect to bladder progression, multivariate analysis showed that pT1 tumors, the appearance of concomitant carcinoma-in situ at the time of the first intravesical relapse, and the absence of the Bacillus Calmette-Guérin treatment were independent risk factors.

Conclusions

This retrospective study presents a detailed picture of further bladder outcomes after intravesical recurrence after RNU in primary UTUC patients. The results may assist physicians to develop a more rational protocol in bladder surveillance.     

Prognostic significance of tumor location and superficial urothelial bladder carcinoma history in patients with ureteral urothelial carcinoma treated with radical nephroureterectomy

Purpose

To investigate the significance of tumor location and superficial urothelial bladder carcinoma (UBC) history on oncological outcomes in patients treated with radical nephroureterectomy (RNU) for ureteral urothelial carcinoma (UC).

Methods

One hundred and thirty-two patients treated with RNU for ureteral UC between January 1999 and July 2010 were retrospectively analyzed. Recurrence probabilities and survival rates were analyzed, stratified by tumor location and superficial UBC history.

Results

Comparison of patients with proximal, middle, and distal ureteral UC showed that percentage of bladder recurrence was 13.3, 14.7, and 25.0 %, respectively (P = 0.285); retroperitoneal (tumor bed or lymph node) recurrence was 26.7, 14.7, and 27.9 % (P = 0.319); and contralateral recurrence was 0, 2.9, and 0 % (P = 0.234). Comparison of patients with and without history of superficial UBC revealed that percentage of bladder recurrence was 15.4 and 20.2 %, respectively (P = 0.681); retroperitoneal recurrence was 15.4 and 25.2 % (P = 0.433); and contralateral recurrence was 0 and 0.84 % (P = 0.740). Using multivariable Cox regression analyses, there were no significant differences of recurrence-free survival (RFS) and cancer-specific survival (CSS) with regard to neither tumor location nor superficial UBC history (RFS: P = 0.282 and 0.762, CSS: P = 0.272 and 0.818, respectively).

Conclusions

Tumor location and history of superficial UBC could not be used to predict oncological outcomes of patients who underwent RNU for ureteral UC. Therefore, operative strategies or postoperative surveillance should not be affected by tumor location or history of superficial UBC.     

The oncologic impact of a delay between diagnosis and radical nephroureterectomy due to diagnostic ureteroscopy in upper urinary tract urothelial carcinomas: results from a large collaborative database

Objectives

According to the current upper urinary tract urothelial carcinomas (UTUC) guidelines, ureteroscopic evaluation (URS) is recommended to improve diagnostic accuracy and obtain a grade (by biopsy or cytology). However, URS may delay radical surgery [e.g., nephroureterectomy (RNU)]. The objective of this study was to evaluate the influence of URS implementation before RNU on patient survival.

Methods

A French multicentre retrospective study including 512 patients with nonmetastatic UTUC was conducted between 1995 and 2011. Achievement of ureteroscopy (URS), treatment time (time between imaging diagnosis and RNU), tumour location, pT–pN stage, grade, lymphovascular invasion (LVI) and the presence of invaded surgical margins (R+) were evaluated as prognostic factors for survival using univariate and multivariate Cox regression analyses. Cancer-specific survival (CSS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were calculated using the Kaplan–Meier method.

Results

A total of 170 patients underwent ureteroscopy prior to RNU (URS+ group), and 342 did not undergo URS (URS?). The median treatment time was significantly longer in the URS+ group (79.5 vs. 44.5 days, p = 0.04). Ureteroscopic evaluation was correlated with ureteral location and lower stage and tumour grade (p = 0.022, 0.005, 0.03, respectively). Tumour stage, LVI+ and R+ status were independently associated with CSS (p = 0.024, 0.049 and 0.006, respectively). The 5-year CSS, RFS and MFS did not differ between the two groups (p = 0.23, 0.89 and 0.35, respectively). These results were confirmed for muscle-invasive (MI) UTUC (p = 0.21, 0.44 and 0.67 for CSS, RFS and MFS, respectively).

Conclusions

Despite the increased time to radical surgery, diagnostic ureteroscopy can be systematically performed for the appraisal of UTUC to refine the therapeutic strategy without significantly affecting oncological outcomes, even for MI lesions.     

Perforation during TUR of bladder tumours influences the natural history of superficial bladder cancer

Objectives

Bladder perforation is the second most common complication during transurethral resection of bladder tumours. It is unknown whether perforation affects the natural history of the tumour through cell seeding. The aim of this study was to study the impact of perforation on the oncologic outcomes of bladder carcinoma.

Materials and methods

Between 2003 and 2007, 926 consecutive patients underwent transurethral resection of bladder tumours at our institution; 327 cases were staged ≥pT2 and were treated immediately with cystectomy and/or multimodal therapy and therefore excluded from the study. An additional 34 cases without urothelial carcinoma were excluded. Of the remaining 565 patients with non-muscle invasive bladder cancer, 457 (80.8 %) were male and 108 (19.2 %) were female with a mean age of 69.5 years in men and 67.3 years in women. Thirty-seven patients (6.5 %) experienced bladder perforation at the time of tumour resection. This group of patients (Group 1) was compared to the remaining 528 patients (Group 2) who did not experience a bladder perforation.

Results

Patients with bladder wall perforation experienced a shorter disease-free survival in both univariate (p = 0.003) and multivariate analyses (p = 0.006). In addition, subsequent recurrences revealed stage progression of recurrent disease (p = 0.05) and trended to a higher number of cystectomies in the perforated group of patients (p = 0.06). Nevertheless, perforation did not appear to influence overall survival (p = 0.127) or cancer-specific survival (p = 0.141).

Conclusion

The results indicate that bladder perforation during resection of superficial bladder tumours is burdened by a shortened disease-free survival and T-stage progression.     

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent

Background

Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients.

Methods

Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models.

Results

ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively).

Conclusions

ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

     

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer

Purpose

To evaluate whether anti-inflammatory agents affect outcomes in patients receiving intravesical BCG therapy for high-grade (HG) non-muscle-invasive bladder cancer (NMIBC).

Methods

We reviewed the records of 203 patients in a prospective database of HG NMIBC from 2006 to 2012 at a single institution. Patients who had muscle-invasive disease (n = 32), low-grade pathology (n = 4), underwent early cystectomy within 3 months (n = 25), had <3 months of follow-up (n = 11), or did not receive an induction course of intravesical BCG (n = 32) were excluded. Clinicopathologic data were tabulated including demographics, comorbidities, pathologic stage and grades, intravesical therapy, and concomitant use of aspirin, NSAIDs, COX inhibitors, and statins. Multivariate Cox regression analysis explored predictive factors for recurrence, progression (stage progression or progression to cystectomy), cancer-specific survival (CSS), and overall survival (OS).

Results

Ninety-nine patients with HG NMIBC who received at least one induction course of intravesical BCG were identified, with median follow-up of 31.4 months. There were 20 (20.2 %) deaths, including 6 (6.1 %) patients with bladder cancer-related mortality. 13 % patients experienced tumor progression and 27 % underwent cystectomy following failure of intravesical therapy. Anti-inflammatory use included statins (65 %), aspirin (63 %), or non-aspirin NSAIDs/COX inhibitors (26 %). Anti-inflammatory use was not significantly predictive of recurrence, progression, or mortality outcomes on Cox regression. CIS stage was associated with higher progression, while age, BMI, and Charlson score were independent predictors of overall mortality.

Conclusion

Despite speculation of inhibitory effects on BCG immunomodulation there was no evidence that anti-inflammatory agents impacted oncologic outcomes in patients receiving BCG for HG NMIBC.

     

Predictors of Survival in Patients With Soft Tissue Surgical Margin Involvement at Radical Cystectomy

Background

The presence of positive soft tissue surgical margins (STSM) at radical cystectomy (RC) is rare. Although some patients with STSM experience disease recurrence rapidly, some have long-term local disease control. We sought to describe the oncologic outcomes, identify predictors, and assess the impact of location and multifocality in patients with positive STSMs at RC.

Methods

We retrospectively collected the data of 4,335 patients treated with RC and pelvic lymphadenectomy at 11 academic centers from 1981 to 2008. STSM was defined as the presence of tumor at inked areas of soft tissue on the RC specimen. Univariate and multivariate Cox regression models addressed recurrence-free survival and cancer-specific survival after surgery.

Results

STSM were identified in 231 patients (5 %). Actuarial recurrence-free survival estimates at 2 and 5 years after RC were 26 ± 3 and 21 ± 3 %, respectively. Actuarial cancer-specific survival estimates at 2 and 5 years after RC were 33 ± 3 and 25 ± 4 %, respectively. Higher body mass index (p = 0.050), higher tumor stage (p = 0.017), presence of grade 3 disease (p = 0.046), lymphovascular invasion (p = 0.003), and lymph node involvement (p = 0.003) were all independently associated with disease recurrence. Furthermore, higher tumor stage (p = 0.015), lymphovascular invasion (p = 0.006), and lymph node involvement (p = 0.006) were independently associated with cancer specific mortality. Location and multifocality of STSM were not associated with outcomes.

Conclusions

Although most patients with STSM at RC had poor outcomes, more than one-fifth had durable cancer control. Pathologic features associated with disease recurrence in the general RC population also stratify patients with STSM into differential risk groups.     

Laparoscopic radical nephroureterectomy is associated with worse survival outcomes than open radical nephroureterectomy in patients with locally advanced upper tract urothelial carcinoma

Purpose

To compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in upper urinary tract urothelial carcinoma (UTUC) patients.

Methods

We retrospectively analyzed the data of 371 UTUC patients who underwent ORNU (n = 271) or LRNU (n = 100) between 1992 and 2012. The survival outcomes included intravesical recurrence (IVR)-free survival, overall survival (OS), and cancer-specific survival (CSS). The Kaplan–Meier method and log-rank test were used to estimate and compare survival curves between groups. Factors associated with survival outcomes were evaluated using univariable and multivariable Cox proportional hazard models.

Results

The three-year IVR-free survival rates were similar between the ORNU and LRNU groups (59.9 and 61.7 %, p = 0.267). However, the LRNU group showed worse five-year OS (59.1 vs. 75.2 %, p = 0.027) and CSS (66.1 vs. 80.2 %, p = 0.015) rates than the ORNU group. In particular, on stratifying the study cohort by pathological stages, significant differences in OS (p = 0.007) and CSS (p = 0.005) between the surgical approaches were observed only in locally advanced disease (pT3/T4). In multivariable analysis, LRNU was an independent predictor of worse OS (p = 0.001) and CSS (p = 0.006) than ORNU. Likewise, in multivariable analysis in patients with pT3/T4 stage, LRNU was significantly associated with worse OS (hazard ratio [HR] 2.59, p = 0.001) and CSS (HR 2.50, p = 0.005).

Conclusions

Our data suggest that in UTUC patients, LRNU, compared to ORNU, is generally associated with unfavorable OS and CSS results. In particular, LRNU should be performed in locally advanced UTUC patients after careful consideration of its impact on patient survival.

     

External Validation of Extranodal Extension and Lymph Node Density as Predictors of Survival in Node-positive Bladder Cancer after Radical Cystectomy

Background

Prognostic factors in pathologic node-positive patients after radical cystectomy are debated. Extranodal extension (ENE) and lymph node density (LND) are strong predictors of survival. The aim of this study was to assess factors predictive of survival and to evaluate the prognostic significance of the tumor, node, metastasis staging system (TNM) nodal classification in a retrospective cohort of node-positive bladder cancers after radical cystectomy.

Methods

We retrospectively reviewed the data of 75 patients with node-positive bladder cancer after radical cystectomy. Node pathological examination was performed by two experienced uropathologists. Cox regression analysis was performed to identify factors predictive of progression.

Results

The median number of removed lymph node was 18 (range 3–49). The median number of positive lymph nodes was 3 (range 1–35). Overall progression-free and cancer-specific survival were 5 and 12 %. In multivariate analysis, ENE, LND with a 20 % cutoff, and adjuvant chemotherapy were independent predictors of progression-free survival (p = 0.007, 0.006, <0.0001). Neither the 2002 nor the 2009 TNM nodal classification was associated with recurrence.

Conclusions

ENE and LND are strong predictors of clinical outcome in patients with node-positive bladder cancer treated by cystectomy. The actual TNM classification could probably be improved using these criteria, allowing better prognostic classification of node-positive bladder cancer after radical cystectomy.     

The prognostic role of pre-cystectomy hemoglobin levels in patients with invasive bladder cancer

Purpose

To determine whether pre-treatment hemoglobin (Hb) levels in patients with bladder cancer impact on oncological outcomes after radical cystectomy (RC).

Methods

A consecutive, contemporary series of 246 patients undergoing RC and pelvic lymph node dissection for bladder cancer. Decreased Hb level was defined as ≤12 g/dL. The Kaplan–Meier method was used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). The Fisher exact/Chi-square test was used to investigate differences between both groups. Uni- and multivariable Cox regression analysis addressed risk factors for recurrence, cancer-specific death and overall death. The median follow-up was 30 months (2–116).

Results

Of the 246 patients, 182 (74 %) had normal (>12 g/dL) and 64 decreased (≤12 g/dL) preoperative Hb (26 %). In univariable analysis, decreased Hb was associated with increased age, extravesical disease, hydronephrosis (all p < 0.001), node-positive disease and positive resection margins (both p = 0.01). Subanalyzed for patients with organ-confined disease (defined as ≤pT2bN0R0; N = 109), the 3-year RFS, CSS and OS was significantly lower in patients with decreased (34.9, 35.5 and 19.8 %) compared to normal Hb level (69.7, 86.3 and 77.6 %; p = 0.01/p = 0.002/p < 0.001). In multivariable analysis, RFS, CSS and OS were significantly lower in patients with decreased Hb (p = 0.007, p = 0.001 and p = 0.002), pathologically locally advanced tumor (≥pT3a; p = 0.023, p = 0.036 and p = 0.065) and nodal stage (p < 0.001, p = 0.006 and p = 0.001) and positive soft tissue surgical margins (p = 0.040, p = 0.004 and 0.012).

Conclusions

Pre-cystectomy Hb levels are associated with adverse histopathologic characteristics and provide additional prognostic information especially for patients with pathologically localized bladder cancer.

     

Adjuvant chemotherapy is associated with decreased mortality after radical cystectomy for locally advanced bladder cancer

Purpose

We sought to evaluate the association of adjuvant chemotherapy with the risk of subsequent mortality among patients with locally advanced urothelial carcinoma (UC) of the bladder undergoing radical cystectomy (RC).

Methods

We identified 675 patients who underwent RC for pT2–4 and/or N+ UC between 1980 and 2005. Adjuvant chemotherapy was defined as treatment within 90 days of RC. Survival was estimated using the Kaplan–Meier method and compared according to receipt of adjuvant chemotherapy with the log-rank test. Multivariate models were used to analyze the impact of adjuvant chemotherapy on disease progression and survival.

Results

A total of 80 (12 %) patients received adjuvant chemotherapy. Median age was 69 years [interquartile range (IQR) 63, 76]. Median follow-up was 11 years (IQR 8, 16). Patients receiving adjuvant chemotherapy were more likely to have pT3–4 tumors (71 vs. 61 %; p < 0.001) and pN+ (85 vs. 19 %; p < 0.001). The 5-year cancer-specific survival was 46 % in those receiving adjuvant chemotherapy and 51 % in those that did not (p = 0.63). The 5-year overall survival was 39 % in those receiving adjuvant chemotherapy and 38 % in those that did not (p = 0.24). When controlling for age, sex, stage, and performance status, adjuvant chemotherapy was associated with a 29 % decrease in the risk of bladder cancer death (HR 0.71, p = 0.06) and a 39 % decrease in the risk of all-cause mortality (HR 0.61, p = 0.002).

Conclusions

After controlling patient and tumor features, adjuvant chemotherapy was associated with a trend toward reduction in cancer-specific mortality and a statistically significant reduction in all-cause mortality.