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.     

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.     

Comparison of microscopic (pT3a) and gross extravesical extension (pT3b) in pathological staging of bladder cancer: analysis of patient outcomes

Objective

To determine the prognostic value of pT3 bladder urothelial carcinoma substaging in patients without lymphatic involvement.

Patients and methods

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1991 and 2010. Of the 460 reviewed patients, 74 patients were diagnosed with pathologic T3No urothelial carcinoma of the bladder. The impact of pathologic substaging (pT3a vs. pT3b) was examined to determine the effect on overall and disease-specific survival.

Results

Five years disease-specific and overall survival rates were 46.9 % and 39.6 % for patients with pT3aNo tumor, whereas these ratios were 34.4 and 30.3 %, respectively, for patients with pT3bNo tumor (p > 0.05). Mean disease-specific survival time was 43.94 ± 6.50 months for pT3aNo, while it was 39.01 ± 7.19 months for pT3bNo (p = 0.539). In multivariate cox regression analysis, age (p = 0.459), gender (p = 0.710), urinary diversion type (p = 0.088), and pT3 substaging (p = 0.554) were not noticed as an independent predictive factor for survival.

Conclusion

Macroscopic extravesical extension (pT3b) is not associated with a worse outcome than pT3a disease in lymph node-negative cases of bladder urothelial carcinoma.     

Downstaging to non-invasive urothelial carcinoma is associated with improved outcome following radical cystectomy for patients with cT2 disease

Introduction

Pathologic stage is a critically important prognostic factor after radical cystectomy (RC) that is used to guide the use of secondary therapies. However, the risk of disease recurrence, for patients clinically diagnosed with muscle-invasive tumors who are found not to have muscle-invasive disease at RC are poorly defined. Therefore, we reviewed the long-term outcomes in patients who were downstaged to non-invasive urothelial carcinoma at time of RC.

Methods

We identified 1,177 consecutive patients with muscle-invasive urothelial carcinoma of the bladder who underwent radical cystectomy at our institution between 1980 and 1999 without neoadjuvant therapy. Postoperative disease recurrence and survival were estimated using the Kaplan?CMeier method and compared using the log rank test. Cox proportional hazard regression models were used to analyze the impact of pathologic stage on survival.

Results

Pathologic downstaging to non-muscle invasive disease was identified in 538 (45.7?%) patients. The 10-year cancer-specific survival was 84.1, 77.4, 71.1 and 58.5?% for those with pT0, pTis, pT1 and pT2 tumors, respectively. On multivariate analysis, the risk of cancer-specific mortality was significantly decreased for patients with non-muscle invasive disease than those with organ-confined muscle invasion (RR?0.39; p?=?0.002). There was no difference in disease-specific mortality among patients who had non-invasive (pT0, pTa, or pTis) disease (p?=?0.19).

Conclusions

Downstaging from clinical muscle-invasive bladder cancer to non-muscle invasive disease at RC is associated with a significant reduction in cancer-specific mortality. However, even patients with residual non-muscle invasive disease may suffer disease recurrence and require continued surveillance after surgery.     

A nomogram predicting the cancer-specific mortality in patients eligible for radical cystectomy evaluating clinical data and neoadjuvant cisplatinum-based chemotherapy

Purpose

Despite the increasing number of studies confirming the importance of neoadjuvant chemotherapy (NC) in patients before radical cystectomy (RC) for bladder cancer (BCa), NC remains underused. The aim of our study was to develop a nomogram predicting the cancer-specific mortality (CSM) of patients who underwent RC for transitional BCa, evaluating the available clinical information and the NC.

Materials and methods

We identified 423 patients who underwent RC and pelvic lymph node dissection, treated or not with NC, in two European high-volume centers between 2007 and 2013. Chi-square and Student’s t tests were used to evaluate differences between groups. Kaplan–Meier curves were used to assess time to cancer-specific (CSS) and overall survival (OS). Uni- (UVA) and multivariable (MVA) Cox regression analyses were developed to address predictors of CSS and OS. A nomogram based on the Cox regression coefficient was developed to show the impact of NC on CSM.

Results

Mean follow-up was 20.3 months. Our population had mainly pT2 disease (77.1 %), and 19.4 % had preoperative cisplatinum-based NC. NC showed better CSS at UVA (p = 0.014) and MVA (odds ratio: 0.44; p = 0.043). Overall, the 3-year OS and the CSS rate were 69.3 and 79 %, respectively. The nomogram developed to predict the 36-month CSM showed predictive accuracy of 67 %.

Conclusions

We developed the first nomogram predicting the 36-month CSM rate in patients with high-risk BCa according to the clinical data. Moreover, we demonstrate that preoperative cisplatinum-based chemotherapy is associated with better CSS.

     

Outcomes following radical cystectomy for micropapillary bladder cancer versus pure urothelial carcinoma: a matched cohort analysis

Purpose

Micropapillary (MP) bladder cancer is a rare variant of urothelial carcinoma (UC) which has been associated with an aggressive natural history. We sought to report the outcomes of patients with MP bladder cancer treated with radical cystectomy (RC) and compare survival to patients with pure UC of the bladder.

Methods

We identified 73 patients with MP bladder cancer and 748 patients with pure UC who underwent RC at our institution with median postoperative follow-up of 9.6?years. MP patients were stage-matched 1:2 to patients with pure UC. Survival was estimated using the Kaplan?CMeier method and compared with the log-rank test.

Results

MP cancers were associated with a high rate of adverse pathologic features, as 48/73 patients (66?%) had pT3/4 tumors and 37 (50?%) had pN+ disease. Ten-year cancer-specific survival in MP patients was 31?%, compared with 53?% in the overall cohort with pure UC (p?=?0.001). When patients with MP bladder cancer were then stage-matched to those with pure UC, no significant differences between the groups were noted with regard to 10-year local recurrence-free survival (62 vs. 69?%; p?=?0.87), distant metastasis-free survival (44 vs. 56?%; p?=?0.54), or cancer-specific survival (31 vs. 40?%; p?=?0.41).

Conclusion

MP cancers are associated with a higher rate of locally advanced disease. However, when matched to patients with pure UC, patients with MP tumors did not have increased local/distant recurrence or adverse cancer-specific survival following RC.     

Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome

Background

The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome.

Objective

Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients.

Design, setting, and participants

The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy.

Measurements

Patients’ characteristics and outcome were evaluated.

Results and limitations

The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p = 0.002 and p = 0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p = 0.011 and p = 0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes.

Conclusions

In this large international cohort, pathologic substaging helped to stratify patients with lymph node–negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging.     

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.     

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.     

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.

     

Diagnostic Ureteroscopy Independently Correlates with Intravesical Recurrence after Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma

Background

Little is known about the effects of diagnostic ureteroscopy on intravesical recurrence after nephroureterectomy.

Methods

This study was designed to determine the effect of diagnostic ureteroscopy on intravesical recurrence after nephroureterectomy. From 2004 to 2010, 446 patients underwent nephroureterectomy for upper urinary tract cancer at our tertiary medical center. We included 115 patients who underwent preoperative diagnostic ureteroscopy and 281 patients who did not. This study analyzed the impact of the reported risk factors and diagnostic ureteroscopy for intravesical recurrence after nephroureterectomy by multivariate Cox regression model.

Results

The rates of metastasis and cancer-specific mortality did not differ significantly between the two groups. Diagnostic ureteroscopy was associated with a higher incidence of intravesical recurrence in patients with (p = 0.02) and without (p = 0.016) a previous history of bladder cancer. Ureter tumor biopsy (p = 0.272) and ureter involvement (p = 0.743) were not associated with the rate of intravesical recurrence in this study. Multivariate Cox regression analysis showed that only bladder cancer history (p < 0.001), multifocal tumor (p = 0.05), and diagnostic ureteroscopy (p = 0.05) were independently associated with intravesical recurrence.

Conclusions

Diagnostic ureteroscopy for upper urinary tract cancer was not associated with metastasis and cancer-specific mortality. However, ureteroscopy was associated with an increased incidence of intravesical tumor recurrence. Methods of prevention should be considered to decrease intravesical recurrence and avoid repeated surgical interventions or the development of advanced bladder disease in patients at risk.     

Clinical role of additional adjuvant chemotherapy in patients with locally advanced urothelial carcinoma following neoadjuvant chemotherapy and cystectomy

Purpose

Neoadjuvant chemotherapy (NAC) can downstage invasive bladder cancers prior to radical cystectomy (RC) and improve overall survival. However, the optimal management in patients with persistent non-organ confined disease (pT3–T4 and/or pN+) following RC has not been completely defined. The aim of this study was to describe outcomes associated with the use of adjuvant chemotherapy (AC) in patients with residual non-organ confined cancer at RC following NAC.

Materials and methods

Using data from a high-volume referral institution, pT3–T4 and/or pN+ patients who received NAC and then also RC were identified. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed with Kaplan–Meier analysis.

Results

From 2001 to 2013, 161 patients received NAC and then RC. Eighty-eight pT3–T4 and/or pN+ patients were identified. Twenty-nine (33 %) received AC. Adjuvant chemotherapy in the majority of patients was carboplatin-based (16), followed by cisplatin (8) and other, mainly taxane-containing regimens (5). The median RFS was 17.5 months in the AC and 13.7 months in the non-AC group (p = 0.78). AC remained an insignificant predictor for RFS after adjusting for pT, pN and margin status (HR 0.89, 95 % CI 0.48–1.68]). CSS was 23 and 22 months (p = 0.65) and remained insignificant after adjusting for pathologic confounders.

Conclusions

In our current study population, adjuvant conventional cytotoxic chemotherapy was not associated with significant improvements in RFS or CSS. The choice of AC regimens, and incorporation of newer treatments, may be the key for improving outcomes in this high-risk patient group.

     

Relative contraindications for percutaneous tracheostomy: from the surgeons’ perspective

Purpose

Percutaneous tracheostomy (PT) has gained worldwide acceptance as a bedside procedure by intensivists, but its popularity has declined based on reports of some relative contraindications. The aim of this study was to ascertain the perioperative comorbidities of PT when it is performed by surgeons with experience performing standard tracheostomy.

Methods

Prospective data were collected and analyzed for consecutive PTs performed in intensive care units.

Results

No procedure-related mortality occurred in the present study. No significant differences in perioperative comorbidities, such as transient hemodynamic instability and postoperative wound infection, were noted between the relative contraindication (RC) and normal condition (NC) groups. Otherwise, instrument failure (5 cases, p = 0.052) and procedure failure (2 cases, p = 0.222) occurred in the RC group, but not in the NC group. Two patients in the NC group and one patient in the RC group needed to undergo a reoperation to check for bleeding. In a subgroup analysis, more bleeding events were noted for the patients with coagulopathy (p = 0.057), and premature extubation of the endotracheal tube/instrument failure (p = 0.073) was more common in the patients with neck anatomical difficulty in the RC group.

Conclusions

For patients with relative contraindications, the potential of using PT should be determined on an individual basis. Special attention should be paid to the possibility of instrument failure and bleeding events for the patients with relative contraindications for PT.     

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.     

Factors Influencing the Length of Stay after Radical Cystectomy: Implications for Cancer Care and Perioperative Management

Introduction

Although radical cystectomy (RC) is the gold standard treatment for muscle invasive bladder cancer it is associated with perioperative complications, readmissions, and a prolonged length of hospital stay (PLOS). We explored the perioperative factors associated with a PLOS after RC and subsequent long-term outcomes.

Material and Methods

Consecutive patients with urothelial bladder cancer undergoing RC with curative intent at our institution were classified into two groups: LOS <12 days and PLOS ≥12 days. Clinicopathological variables were compared on univariate and multivariable analysis. Complications, re-admissions, adjuvant chemotherapy use, recurrence free survival (RFS), and overall survival (OS) were compared between the two groups. Competing risk analysis was performed for bladder cancer specific mortality (BCSM).

Results

330 patients were included in the analysis (median LOS = 9 days [IQR = 8–11]) of which, 274 patients (83 %) had a LOS <12 days (median = 8 days [IQR = 7–10]) and 56 patients (17 %) had a PLOS ≥12 days (median = 16 days [IQR = 13–21.5]). Only female gender, older age, and perioperative complications were associated with a PLOS. 90 day readmission rates were similar (p = 0.75). No difference was seen for BCSM, RFS, or adjuvant chemotherapy usage between the two groups. However, OS was significantly worse for PLOS (median OS = 27.7 vs. 45.6 months [p = 0.046]; HR = 1.53 [95 % CI = 1.01–2.33]).

Conclusion

Both female and elderly patients should receive preoperative counseling about their increased risk of a PLOS after RC. Patients who experience a PLOS are at greater risk for subsequent all-cause mortality. These patient groups may benefit from proactive interventions.     

Radical cystectomy for recurrent urothelial carcinoma after prior partial cystectomy: perioperative and oncologic outcomes

Purpose

To evaluate perioperative and oncologic outcomes of patients undergoing radical cystectomy (RC) for recurrence of urothelial carcinoma (UC) after prior partial cystectomy (PC), and to compare these outcomes to patients undergoing primary RC.

Methods

Patients who underwent RC for recurrence of UC after prior PC were matched 1:3 to patients undergoing primary RC based on age, pathologic stage, and decade of surgery. Perioperative and oncologic outcomes were compared using Wilcoxon sign-rank test, McNemars test, the Kaplan–Meier method, and Cox proportional hazards regression analyses.

Results

Overall, the cohorts were well matched on clinical and pathological characteristics. No difference was noted in operative time (median 322 versus 303 min; p = 0.41), estimated blood loss (median 800 versus 700 cc, p = 0.10) or length of stay (median 9 versus 10 days; p = 0.09). Similarly, there were no differences in minor (51.7 versus 44.3%; p = 0.32) or major (10.3 versus 12.6%; p = 0.66) perioperative complications. Median follow-up after RC was 5.0 years (IQR 1.5, 13.1 years). Notably, CSS was significantly worse for patients who underwent RC after PC (10 year—46.8 versus 65.9%; p = 0.03). On multivariable analysis, prior PC remained independently associated with an increased risk of bladder cancer death (HR 2.28; 95% CI 1.17, 4.42).

Conclusions

RC after PC is feasible, without significantly adverse perioperative outcomes compared to patients undergoing primary RC. However, the risk of death from bladder cancer may be higher, suggesting the need for careful patient counseling prior to PC and the consideration of such patients for adjuvant therapy after RC.

     

The importance of clinical stage among patients with a complete pathologic response at radical cystectomy after neoadjuvant chemotherapy

Purpose

Patients without evidence of disease at radical cystectomy (RC) following neoadjuvant chemotherapy (NAC) have the greatest potential for survival in muscle-invasive bladder cancer. Historically, 15 % of such patients will experience disease recurrence and cancer-specific mortality. We sought to evaluate the effect of pre-treatment clinical factors on the risk of recurrence in patients who were ypT0N0 at RC.

Methods

We performed a multi-institutional review of patients treated with NAC + RC for muscle-invasive bladder cancer (≥cT2) without pathologic evidence of disease at surgery (ypT0N0). The association of pre-treatment clinicopathologic features with recurrence was evaluated using Cox proportional hazards.

Results

A total of 78 patients were identified with ypT0 disease at RC after NAC. Median postoperative follow-up was 32.4 months (IQR 16.8, 60.0), during which time 17 patients recurred at a median of 6.4 months after RC. Estimated 3-year recurrence-free survival (RFS) of this cohort was 74.8 %. In univariate analysis, cT4 disease (HR 3.12; p = 0.04) and time to RC (HR 1.17 for each month increase; p < 0.01) were associated with inferior RFS.

Conclusion

Patients without evidence of disease at the time of RC are still at risk of recurrence and death from bladder cancer. Higher clinical stage and increased time to RC were associated with an increased risk of recurrence and subsequent death. These data highlight the importance of timely RC and the continued risk of recurrence in higher clinically staged patients—underscoring the need for close monitoring and patient counseling.

     

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.     

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.     

Sub-classification of Stage II colorectal cancer based on clinicopathological risk factors for recurrence

Purpose

To make a Stage II colorectal cancer (CRC) sub-classification based on clinicopathological factors.

Methods

The subjects of this study were 422 patients with Stage II CRC, who underwent curative surgery with dissection of more than 12 lymph nodes. We used the logistic regression analysis or model and Cox’s proportional hazard regression model for analysis.

Results

Preoperative carcinoembryonic antigen (CEA) level (p = 0.0057), macroscopic type (p = 0.0316), and depth of invasion (p = 0.0401) were extracted as independent risk factors for recurrence, whereas the preoperative CEA level (p = 0.0045) and depth of invasion (p = 0.0395) were extracted as independent predictors of 5-year disease-free survival. We defined depth of invasion (pT4) and the preoperative CEA level (abnormal) as risk factors for recurrence, and classified Grade A as a normal CEA level regardless of depth invasion, Grade B as depth of invasion to pT3 and an elevated CEA level, and Grade C as depth of invasion to pT4 and an elevated CEA level. There were significant differences in cumulative 5-year disease-free survival rates among each grade (Grade A vs. Grade B, p = 0.0474; Grade A vs. Grade C, p < 0.0001; Grade B vs. Grade C, p = 0.0134).

Conclusion

The sub-classification of Stage II CRC, according not only to depth of invasion but also to preoperative CEA level, is important for predicting the prognosis.