Long-term outcome of radical cystectomy in ESDR patients with bladder urothelial carcinoma

Purpose  

The prevalence of urothelial carcinoma is high in dialysis patients. Radical cystectomy is an invasive procedure for patients with recurrent, multiple, or invasive bladder cancer. However, the prognosis of radical cystectomy in dialysis patients has rarely been reported. This study investigates the long-term outcome of radical cystectomy in dialysis patients with bladder urothelial carcinoma.     

Early oncological outcomes for bladder urothelial carcinoma patients treated with robotic-assisted radical cystectomy

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To determine oncological outcomes including early survival rates among unselected bladder urothelial carcinoma (BUC) patients treated with robotic‐assisted radical cystectomy (RRC).

PATIENTS AND METHODS

• ? Clinicopathologic and survival data were prospectively gathered for 85 consecutive BUC patients treated with RRC.
• ? The decision to undergo a robotic rather than open approach was made without regard to tumor volume or surgical candidacy.
• ? Kaplan–Meier survival rates were determined and stratified by tumor stage and LN positivity, and multivariate analysis was performed to identify independent predictors of survival.

RESULTS

• ? Patients were relatively old (25% >80 years; median 73.5 years), with frequent comorbidities (46% with ASA class ≥3). Of these patients 28% had undergone previous pelvic radiation or pelvic surgery, and 20% had received neoadjuvant chemotherapy.
• ? Extended pelvic lymphadenectomy was performed in 98% of patients, with on average 19.1 LN retrieved.
• ? On final pathology, extravesical disease was common (36.5%).
• ? Positive surgicalmargins were detected in five (6%) patients, all of whom had extravesical tumors with perineural and/or lymphovascular invasion, and most of whom were >80 years old.
• ? At a mean postoperative interval of 18 months, 20 (24%) patients had developed recurrent disease, but only three (4%) patients had recurrence locally. Disease‐free, cancer‐specific and overall survival rates at 2 years were 74%, 85% and 79%, respectively. Patients with low‐stage/LN(?) cancers had significantly better survival than extravesical/LN(?) or any‐stage/LN(+) patients, with stage being the most important predictor on multivariate analysis.

CONCLUSION

• ? RRC can achieve adequately high LN yields with a low positive margin rate among unselected BUC patients.
• ? Early survival outcomes are similar to those reported in contemporary open series, with an encouragingly low incidence of local recurrence, however long‐term follow‐up and head‐to‐head comparison with the open approach are still needed.

     

Impact of preoperative serum albumin-globulin ratio on disease outcome after radical cystectomy for urothelial carcinoma of the bladder

IntroductionThe Albumin-Globulin Ratio (AGR; albumin/total protein ? albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB.Material and MethodsWe conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA).ResultsOverall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1–1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1–1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07–1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy.ConclusionpAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation.     

Thromboembolic events in patients with urothelial carcinoma undergoing neoadjuvant chemotherapy and radical cystectomy

ObjectivesPatients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of this study was to assess the effect of cisplatin-based neoadjuvant chemotherapy (NCT) on the incidence of perioperative TEEs in patients undergoing radical cystectomy.Methods and materialsWe analyzed a consecutive sample of 202 patients with urothelial carcinoma treated with radical cystectomy between 2005 and 2013. Data were collected retrospectively by reviewing medical records. Median follow-up was 16.9 months. Events of interest were defined as venous or arterial TEEs occurring from the date of diagnosis to 30 days after surgery. TEE incidence among patients treated with NCT and cystectomy was compared with that among patients treated with cystectomy alone using Fisher exact test and Cox proportional hazards regression. Proportional hazards regression was also used to assess whether TEE is a predictor of cancer progression and survival.ResultsOf 202 patients, 17 (8.4%) developed a TEE, including 8 of 42 (19.1%) treated with NCT and cystectomy and 9 of 160 (5.6%) treated with cystectomy alone (risk ratio = 3.39, 95% CI: 1.39–8.24). After adjustment for observation time, there remained an association between treatment with NCT and risk of TEE (hazard ratio = 2.40; 95% CI: 0.92–6.27; P = 0.07). Overall, 7 events occurred before cystectomy and 10 occurred postoperatively. Among patients treated with NCT, 6 of 8 events occurred before cystectomy. Detection of TEE was clinically significant as preoperative TEE was found to be an independent predictor of progression and cancer-specific mortality (adjusted hazard ratio = 3.91, 95% CI: 1.34–11.45). The main limitations of our study are its retrospective data collection and small absolute number of events.ConclusionsTEE occurs commonly in patients with urothelial carcinoma undergoing NCT. Preoperative TEE is an independent predictor of progression and cancer-specific mortality.     

T2期膀胱尿路上皮癌膀胱部分切除术和根治性膀胱切除术的比较分析

2.4     

NLR is predictive of upstaging at the time of radical cystectomy for patients with urothelial carcinoma of the bladder

ObjectiveTo evaluate the ability of preoperative neutrophil-lymphocyte ratio (NLR) to predict pathologic upstaging and nonorgan-confined (NOC) (≥pT3) disease.Methods and materialsAfter institutional review board approval, the records of consecutive patients undergoing radical cystectomy (RC) for urothelial carcinoma from 2002 to 2012 at the University of Wisconsin Hospital were reviewed. A total of 102 patients with NLR within 100 days of surgery were eligible for analysis. The primary outcome was difference in stage from preoperative assessment to time of RC. Differences in preoperative NLR between groups were evaluated with an unequal variance t test. A univariate analysis assessed whether NLR, preoperative stage, grade, associated lymphovascular invasion, preoperative hydronephrosis, gender, previous pelvic radiotherapy, previous intravesical bladder cancer treatments, or nodal stage were related to upstaging. Multivariate analyses were performed to evaluate the relationship of NLR to upstaging and relative organ-confined (≤pT2) and NOC disease.ResultsOf 390 consecutive patients undergoing RC, 102 patients met study criteria. Overall, 55 (53.9%) patients were upstaged, 25 (25.5%) were unchanged, and 21 (20.6%) were downstaged. Fifty-one patients (50%) were upstaged to more advanced disease (≥pT3). NLR and preoperative hydronephrosis were significantly related to pathologic tumor staging. NLR, preoperative hydronephrosis, and preoperative tumor stage were significantly related to upstaging to NOC disease. Patients who were upstaged to≥pT3 demonstrated statistically significant greater NLRs (4.33±0.87) compared with patients who remained at≤pT2 stage (2.66±0.29) (P<0.001).ConclusionsPreoperative NLR is a simple measurement that can be used to identify high-risk patients who may be upstaged at the time of RC and may benefit from neoadjuvant chemotherapy.     

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy

ObjectiveCarcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC).Materials and methodsA multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower.ResultsConcomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients.ConclusionThe presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.     

Adjuvant chemotherapy versus observation following radical cystectomy for locally advanced urothelial carcinoma of the bladder

BackgroundThe role of adjuvant chemotherapy (AC) in patients with locally advanced bladder cancer following radical cystectomy (RC) remains uncertain, with contemporary clinical trials underpowered and closed early due to low accrual.ObjectiveTo conduct observational analyses designed to emulate a completed randomized trial of AC in patients with locally advanced bladder cancer.Design, Settings, and ParticipantsBased on EORTC 30994 eligibility criteria, we identified adult patients aged 35 to 75 with pT3/pT4 Nany M0 or Tany pN1-3 M0, R0 urothelial carcinoma of the bladder treated with RC and lymphadenectomy from 2006 to 2015 in the National Cancer Database.Outcome Measurements and Statistical AnalysisA propensity score for receipt of AC within 3 months of RC was estimated, and the associations of AC with overall survival were evaluated after reweighting by stabilized inverse probability of treatment weights.ResultsOf the 2,416 patients who met inclusion criteria, 945 (39%) received AC after RC. After propensity score adjustment, baseline characteristics were well-balanced. Median follow-up was 26.0 months. After IPW-reweighting, overall survival was 43% vs. 36% at 5-years and 34% vs. 24% at 10-years, among those who did and did not receive AC, respectively (P < 0.01). In IPW-adjusted Cox regression models, AC was associated with improved all-cause mortality (HR 0.71; 95% CI 0.63–0.81; P < 0.01). Estimates were overall consistent in analyses that examined heterogeneity of treatment effects. Limitations include unmeasured confounding, selection bias, and lack of baseline renal function data.ConclusionIn observational analyses designed to emulate EORTC 30994, AC was associated with improved overall survival compared to observation after RC. Results were consistent across baseline patient and tumor characteristics.     

Loss of SPINK1 expression is associated with unfavorable outcomes in urothelial carcinoma of the bladder after radical cystectomy

BackgroundWe assessed the association of serine protease inhibitor Kazal type I (SPINK1) expression with clinicopathologic outcomes in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC).Materials and methodsTissue microarrays comprising 438 consecutive UCB patients treated with RC between 1988 and 2003 and 62 cases of normal urothelium controls were evaluated for SPINK1 protein expression by immunohistochemistry (IHC). Semiquantitative evaluation was performed by 2 pathologists blinded to clinical outcomes (loss of expression: <50% cells or intensity 0–2).ResultsIn normal urothelium, SPINK1 expression was noted in umbrella cells of 32 of 62 controls (52%); 254 RC patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with higher pathologic stages (P = 0.002) and presence of lymph node metastasis (P = 0.04). At a median follow-up of 130 months (IQR: 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (P = 0.02) and cancer-specific mortality (P = 0.03). On multivariable analysis that adjusted for the effects of standard clinicopathologic parameters, SPINK1 was not an independent predictor of disease recurrence (P = 0.09) or cancer-specific mortality (P = 0.12).ConclusionsOver half of UCB patients treated with RC exhibit loss of SPINK1 expression. Loss of SPINK1 correlates with features of biologically aggressive UCB. Although SPINK1 expression did not have independent prognostic value in RC patients, it may serve as a biomarker for tumor staging and may be useful as an adjunct in clinical decision-making.     

P0 stage at radical cystectomy for bladder cancer is associated with improved outcome independent of traditional clinical risk factors

OBJECTIVES: Final pathologic specimen free of detectable disease (P0) is not uncommon in patients undergoing cystectomy for bladder cancer, especially in the era of neoadjuvant chemotherapy. To improve our understanding of its significance in a contemporary series, we performed an outcomes analysis of this cohort of patients. METHODS: Over the last 15 yr, 1104 patients with bladder cancer underwent radical cystectomy at our institution. Of these, 120 (11%) were pT0N0M0 (P0) in the surgical specimen and form the basis of this report. Survival data were estimated by method of Kaplan and Meier, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied. RESULTS: Clinical stages were cT1, 21 patients; cT2, 65; cT3b, 20; cT4a, 11; and cT4b, 3. The 5-yr estimates of overall (OS), disease-specific (DSS), and recurrence-free survival (RFS) rates were 84%, 88%, and 84%, respectively. With mean follow-up of 43 mo, 11 patients developed recurrences, 9 of whom died of disease. Median time to recurrence was 7.7 mo (range: 2.2-45 mo). On multivariate analysis, presence of lymphovascular invasion and concomitant carcinoma in situ on the transurethral resection of the bladder tumor specimen were the only significant prognostic factors associated with shorter OS (p = 0.04) and RFS (p = 0.049), respectively. Notably, patients who received preoperative chemotherapy (n = 77) had 5-yr survival rates similar to those of patients who did not. CONCLUSION: Although patients who are P0 at cystectomy have a good prognosis, not all can be considered cured. The favorable prognosis conferred by a P0 state appears to be independent of whether this is achieved by neoadjuvant chemotherapy or by thorough transurethral resection before cystectomy.     

Variability of treatment selection among surgeons for patients with cT1 urothelial carcinoma

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVES

To report the heterogeneity in the treatment of patients with cT1 urothelial carcinoma by different surgeons, and to report outcomes in patients with and without bacillus Calmette‐Guérin (BCG) treatment.

PATIENTS AND METHODS

We retrospectively reviewed 396 patients who had undergone a re‐staging transurethral resection (TUR) for cT1 bladder cancer. We assessed both differences in the treatment by surgeon, and the association of early treatment with BCG with recurrence, progression and bladder cancer‐specific death.

RESULTS

Muscle was captured in the re‐staging TUR specimen in a median of 76% of patients (range 50–94 when stratified by surgeon). On multivariable analysis there was significant heterogeneity among surgeons in the use of early cystectomy (P < 0.001), deferred cystectomy (P < 0.001), and BCG (P= 0.014). However, there was no significant heterogeneity between surgeons in clinical outcome for recurrence (P= 0.9) and overall survival (P= 0.3). Among 288 patients placed on surveillance, the 5‐year probability (95% confidence interval) of freedom from recurrence was 45 (36–54)% for those receiving and 54 (44–62)% for those not receiving early BCG. On multivariable analysis, early BCG was not significantly associated with recurrence (P= 0.14). The cumulative incidence of progression was ≈10% for both groups, and the cumulative incidence of bladder cancer‐specific death was ≈7% for both groups. The cumulative incidence of deferred cystectomy before progression was 14% for those receiving and 15% for those not receiving early BCG.

CONCLUSIONS

There is a significant variability among surgeons in the management of patients with T1 disease. The similar outcome for the BCG‐treated and ‐untreated patients in our study is most likely confounded by patient selection.     

Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: A multi-institutional investigation

Purpose

To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy.

Kidney disease progression in patients of upper tract urothelial carcinoma following unilateral radical nephroureterectomy

Objectives: To compare the renal outcomes in patients of unilateral renal cell carcinoma (RCC) with upper tract urothelial carcinoma (UTUC) following surgical resection of the tumor-bearing kidney, and to investigate the potential predictors in renal function decline. Patients and methods: In this retrospective cohort study, 319 RCC patients undergoing radical nephrectomy (RN) and 297 UTUC patients undergoing radical nephroureterectomy were recruited from a tertiary medical center between 2001 and 2010. Demographic data, co-morbidity, smoking habit, baseline estimated glomerular filtration rate (eGFR) calculated by chronic kidney disease-epidemiology equation, as well as tumor staging of RCC and UTUC, were recorded. The primary endpoint was serum creatinine doubling and/or end-stage renal disease (ESRD) necessitating long-term dialysis. Cox proportional hazard model and Fine and Gray's competing risk regression accounting for death were used to model renal outcome. Results: UTUC patients had a higher incidence rate of renal function deterioration than RCC patients did (15.01 vs. 2.68 per 100 person-years, p<0.001). In Cox proportional hazard model and Fine and Gray's competing risk regression, UTUC was significantly associated with increased risk of creatinine doubling and/or ESRD necessitating dialysis (hazard ratio, 3.13; 95% confidence interval, 2.01–4.87) as compared to RCC following unilateral RN. Nevertheless, our study is observational in nature and cannot prove causality. Conclusions: UTUC per se is strongly associated with kidney disease progression as compared to RCC following unilateral nephrectomy. Further studies are needed to elucidate this association.     

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.     

Prostatic involvement by urothelial carcinoma of the bladder: clinicopathological features and outcome after radical cystectomy

OBJECTIVES: To review the long-term outcome of prostatic involvement in patients with bladder cancer (BC) treated with radical cystectomy (RC), as urothelial carcinoma (UC) involving the prostate occurs in such patients, and prostatic invasion by UC is by transmural invasion (contiguous), or when UC develops from the epithelium of the prostatic urethra (not contiguous). PATIENTS AND METHODS: Between 1992 and 2006, 351 men had RC for BC by one surgeon at our centre; they were stratified into those with contiguous or non-contiguous disease, based on prostatic stromal involvement. Relevant clinical and pathological data were collected and the survival analysed. RESULTS: In all, 24% (78/320) of the patients who had RC had prostatic involvement; 29 (9%) and 49 (15%) had contiguous and non-contiguous involvement, respectively. In the non-contiguous group, there was stromal and non-stromal UC involvement in 18 (37%) and 31 (63%), respectively. The overall 5-year survival of contiguous, non-contiguous and no prostatic involvement was 6%, 57% and 66% (P < 0.001). The 5-year overall survival of stromal and non-stromal UC was 26% and 74% (P = 0.008). There was no statistical difference in survival between contiguous and non-contiguous stromal involvement (P = 0.58). CONCLUSIONS: Prostatic UC with no stromal involvement did not alter the survival predicted by the primary bladder stage. Stromal involvement of the prostate has a poor prognosis regardless of the mode of invasion.