Perivesical fat invasion in bladder cancer: implications for prognosis comparing pT2b,pT3a and pT3b stages and consequences for adjuvant chemotherapy indications

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The more that bladder cancer progresses from the urothelium to the outside of the bladder the worse the prognosis. To date, the use of adjuvant chemotherapy has not been completely defined. The present study clarifies the prognosis and benefits of adjuvant chemotherapy for different stages of bladder cancer that invade perivesical fat.

OBJECTIVE

• ? To assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical cystectomy (RC) in order to define potential situations where chemotherapy may be of benefit.

PATIENTS AND METHODS

• ? Between 1985 and 2009, 903 patients underwent a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre.
• ? In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour, and 129 patients (14.3%) a pT3b tumour.
• ? The median (range) overall follow‐up was 23 (1–350) months.
• ? Overall (OS), disease‐specific (DSS), metastases‐free (MFS) and local recurrence‐free survival (LRFS) was estimated and compared using Kaplan–Meier plots and log‐rank test.

RESULTS

• ? The 5‐year survivals pT2b and pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%, 44%, 40%, and 31% respectively).
• ? In pN0 disease, MFS differences between pT2b–pT3a and pT3b tumours were not significant in patients who had received adjuvant chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%, respectively).

CONCLUSIONS

• ? Bladder cancers invading perivesical tissue macroscopically have a greater propensity to produce lymph node metastases, local recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may receive more benefit from adjuvant chemotherapy.
• ? Our results could be a useful for selecting patients for adjuvant chemotherapy.

     

Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? In patients treated with radical cystectomy, pelvic lymph node dissection may have a beneficial effect on cancer control outcomes. We examined the effect of pelvic lymph node dissection on stage‐specific cancer control outcomes.

OBJECTIVE

• ? To examine the effect of stage‐specific pelvic lymph node dissection (PLND) on cancer‐specific (CSM) and overall mortality (OM) rates at radical cystectomy (RC) for bladder cancer.

METHODS

• ? Overall, 11 183 patients were treated with RC within the Surveillance, Epidemiology, and End Results database.
• ? Univariable and multivariable Cox regression analyses tested the effect of PLND on CSM and OM rates, after stratifying according to pathological tumour stage.

RESULTS

• ? Overall, PLND was omitted in 25% of patients, and in 50, 35, 27, 16 and 23% of patients with respectively pTa/is, pT1, pT2, pT3 and pT4 disease (P < 0.001).
• ? For the same stages, the 10‐year CSM‐free rates for patients undergoing PLND compared with those with no PLND were, respectively, 80 vs 71.9% (P = 0.02), 81.7 vs 70.0% (P < 0.001), 71.5 vs 56.1% (P = 0.001), 43.7 vs 38.8% (P = 0.006), and 35.1 vs 32.0% (P = 0.1).
• ? In multivariable analyses, PLND omission was associated with a higher CSM in patients with pTa/is, pT1 and pT2 disease (all P ≤ 0.01), but failed to achieve independent predictor status in patients with pT3 and pT4 disease (both P ≥ 0.05).
• ? Omitting PLND predisposed to a higher OM across all tumour stages (all P ≤ 0.03).

CONCLUSIONS

• ? Our results indicate that PLND was more frequently omitted in patients with organ‐confined disease.
• ? The beneficial effect of PLND on cancer control outcomes was more evident in these patients than in those with pT3 or pT4 disease.
• ? PLND at RC should always be considered, regardless of tumour stage.

     

International validation of the prognostic value of subclassification for AJCC stage pT3 upper tract urothelial carcinoma of the renal pelvis

Study Type – Prognosis (inception cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Tumour stage is a powerful predictor of clinical outcomes and the most important factor driving clinical decision‐making after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). It has been suggested that renal pelvic pT3 subclassification into microscopic infiltration of the renal parenchyma (pT3a) versus macroscopic infiltration or invasion of peripelvic adipose tissue (pT3b) has strong prognostic value. This is an external validation study of the prognostic value of pT3 subclassification of renal pelvic UTUC in a large international cohort of patients treated with RNU. pT3b UTUC is associated with features of aggressive tumour biology, disease recurrence and cancer‐specific mortality. However, pT3 subclassification is not an independent predictor of clinical outcomes.

OBJECTIVE

• ? To externally validate the prognostic value of subclassification of pT3 renal pelvic upper tract urothelial carcinoma (UTUC) in a large international cohort of patients treated with radical nephroureterectomy (RNU).

PATIENTS AND METHODS

• ? The RNU specimens with pT3 UTUC of the renal pelvis from 284 patients at 11 centres located in Asia, North America and Europe were retrospectively evaluated. All specimens were reviewed by genitourinary pathologists at each institution. Tumours were categorized as pT3a (microscopic infiltration of the renal parenchyma) or pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue).

RESULTS

• ? Overall, 148 (52%) tumours were classified as pT3a and 136 (48%) as pT3b. Patients with pT3b disease were more likely to have high‐grade tumours and sessile tumour architecture (all P≤ 0.02). Patients with pT3b tumours were at increased risk of disease recurrence (5‐year estimates: 55% versus 42%, P= 0.012) and cancer‐specific mortality (CSM) (5‐year estimates: 48% versus 40%, P= 0.04). Lymph node status, tumour architecture and tumour grade were independently associated with disease recurrence, whereas lymph node status, tumour architecture and lymphovascular invasion were independently associated with CSM. Subclassification of pT3 tumours was not associated with recurrence or CSM in multivariable analyses.

CONCLUSION

• ? Patients with pT3b UTUC were more likely to have tumours with aggressive pathological features and were at higher risk of disease recurrence and CSM after RNU compared with patients with pT3a disease. However, the pT3 subclassification did not remain an independent predictor of disease recurrence or CSM after controlling for tumour grade, lymph node status, tumour architecture and lymphovascular invasion.

     

Selective bladder-sparing protocol consisting of induction low-dose chemoradiotherapy plus partial cystectomy with pelvic lymph node dissection against muscle-invasive bladder cancer: oncological outcomes of the initial 46 patients

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? TURBT plus full‐dose chemoradiotherapy (CRT) against MIBC allow more than 40% of patients to spare the bladder while maintaining survival outcomes comparable to those of radical cystectomy (RC) series, contributing to improvement of the patients’ quality of life. Limitations of these protocols, however, include 1) MIBC recurrence in the preserved bladder mainly due to subclinical residual disease in the original MIBC site, 2) potential lack of curative intervention to regional lymph nodes and 3) increased mortality of salvage RC due to previous high‐dose pelvic irradiation. We propose a novel selective bladder‐sparing protocol consisting of induction low‐dose CRT plus consolidative partial cystectomy with pelvic lymph node dissection, which potentially contributes to overcoming the limitations of the conventional bladder‐sparing protocols.

OBJECTIVE

• ? To evaluate oncological outcomes of muscle‐invasive bladder cancer (MIBC) patients who were treated with a selective bladder‐sparing protocol consisting of induction low‐dose chemoradiotherapy (LCRT) plus partial cystectomy (PC) with pelvic lymph node dissection.

PATIENTS AND METHODS

• ? From 1997–2010, 183 consecutive patients with cT2–4aN0M0 bladder cancer (median age 70 years, women/men = 46/137, T2/3/4a = 100/69/14) underwent debulking transurethral resection followed by LCRT (radiation at 40 Gy to the small pelvis concurrently with two cycles of i.v. cisplatin at 20 mg/day for 5 days).
• ? Criteria for PC include: (i) essentially solitary MIBC or intravesically circumscribed tumours (≈25% or less of the bladder in area, excluding the bladder neck and trigone); (ii) no involvement of bladder neck or trigone; and (iii) clinically, no residual disease or minimal amounts of non‐invasive disease in the original MIBC site after LCRT; otherwise, radical cystectomy (RC) is recommended.
• ? Primary and secondary endpoints were cancer‐specific survival (CSS) and intravesical MIBC recurrence‐free survival (MRFS) for bladder‐preserved patients, respectively.

RESULTS

• ? Of the 183 patients, 87 (48%) achieved a clinical complete response after LCRT and 65 (36%) met the PC criteria; 46 (25%) patients actually underwent PC, 86 (47%) had RC, and the remaining 51 (28%) had neither PC, nor RC.
• ? Histological examination of the 46 PC specimens showed residual muscle‐invasive disease in three (7%).
• ? Overall, 5‐year overall survival and CSS rates were 64% and 71%, respectively (median follow‐up for survivors of 45 months).
• ? In the 46 PC patients, neither MIBC, nor pelvic recurrence was observed; 5‐year CSS and MRFS rates were both 100%.
• ? In 13 non‐PC patients who achieved a complete response after LCRT and who met PC criteria but declined PC, 5‐year CSS and MRFS rates were 74% and 81%, respectively; CSS and MRFS were significantly better in the PC group than in the non‐PC group (P= 0.025 and 0.002, respectively).

CONCLUSIONS

• ? In the current selective bladder‐sparing protocol, one‐third of MIBC patients met the PC criteria; when patients from this group underwent PC with pelvic lymph node dissection, their oncological outcomes were excellent.
• ? Consolidative PC potentially reduces MIBC recurrence in the preserved bladder, eventually improving survival in properly selected MIBC patients.

     

RADICAL CYSTECTOMY FOR BCG FAILURE: HAS THE TIMING IMPROVED IN RECENT YEARS?

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? High‐grade Ta‐T1‐carcinoma in situ bladder cancer is a heterogeneous group; long‐term studies have shown that intravesical BCG therapy can be inadequate in a substantial percentage. Despite concerns about delay in performing RC for patients failing one or more courses of BCG, in our study we have not observed a trend towards a lower pathological stage for patients undergoing RC after BCG.

OBJECTIVE

• ? To analyse if there is a trend in recent years towards performing radical cystectomy (RC) before muscle invasion or extravesical spread after failure of bacille Calmette–Guérin (BCG) for high grade Ta/T1 bladder cancer. Although BCG is indicated for prophylaxis after endoscopic tumour resection there is still a risk of progression.

PATIENTS AND METHODS

• ? A retrospective analysis of our RC database (1992–2008) was performed to identify patients who underwent RC after receiving BCG.
• ? Relevant clinical and pathological data for the patients with clinical stage Ta, T1 and/or Tis at initial transurethral resection of bladder tumour were analysed.
• ? Pathological stage and survival for patients undergoing RC from 2003 to 2007 (group 2) were compared with those for patients operated between 1992 and 2002 (group 1).

RESULTS

• ? A total of 152 patients were included (75 in group 2 and 77 in group 1). Both groups were similar in T‐stage before BCG initiation, number of BCG cycles received and time interval to RC.
• ? There was no change in the proportion of patients undergoing RC with ≥pT2 bladder cancer in recent years (P= 0.5).
• ? Fifty‐two percent of group 2 and 43% of group 1 had ≥pT2 BC. The 5‐year survival was similar.

CONCLUSIONS

• ? Despite concerns about delay in performing RC for patients failing one or more courses of BCG we have not observed a trend towards a lower pathological stage for patients undergoing RC after BCG.
• ? A high proportion of patients have muscle‐invasive bladder cancer; more than 10% have lymph node metastasis.

     

Upper urinary tract transitional cell carcinoma: location is not correlated with prognosis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Tumour location has been shown to be of prognostic importance in UUT‐TCC, with tumours of renal pelvis having a better prognosis than ureteral tumours. Patients from Balkan Endemic Nephropathy (BEN) areas had a higher frequency of pelvis tumours. Also, we found that belonging to a BEN area is an independent predictor of disease recurrence.

OBJECTIVE

• ? To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT‐TCC).

PATIENTS AND METHODS

• ? A single‐centre series of 189 consecutive patients who were treated surgically for UUT‐TCC between January 1999 and December 2009 was evaluated.
• ? Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT‐TCC were excluded.
• ? In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour.
• ? Recurrence‐free probabilities and cancer‐specific survival were estimated using the Kaplan–Meier method and Cox regression analyses.

RESULTS

• ? The 5‐year recurrence‐free and cancer‐specific survival estimates for the cohort in the present study were 66% and 62%, respectively.
• ? The 5‐year bladder‐only recurrence‐free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P= 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non‐Balkan endemic nephropathy areas; 95% confidence interval, 1.37–5.98; P= 0.005) were associated with disease recurrence
• ? Tumour location was not associated with disease recurrence in any of the analyses.
• ? There was no difference in cancer‐specific survival between renal pelvis and ureteral tumours (P= 0.476).
• ? Using multivariate analysis, pT classification (HR, 8.04; P= 0.001) and lymph node status (HR, 4.73; P= 0.01) were the only independent predictors associated with a worse cancer‐specific survival.

CONCLUSION

• ? Tumour location is unable to predict outcomes in a single‐centre series of consecutive patients who were treated with radical nephroureterectomy for UUT‐TCC.

     

Risk group stratification to predict recurrence after transurethral resection in Japanese patients with stage Ta and T1 bladder tumours: validation study on the European Association of Urology guidelines

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? EAU guidelines on non‐muscle‐invasive bladder tumours have been widely used for the prediction of recurrence after TUR. However, there are substantial differences in bladder cancer incidence and mortality rates between European countries and Japan. This study provides useful factors for predicting recurrence and validation of EAU guidelines on the risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.

OBJECTIVE

• ? To validate the European Association of Urology (EAU) guidelines on risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.

PATIENTS AND METHODS

• ? A cohort of 592 Japanese patients who were treated with transurethral resection (TUR) and histopathologically diagnosed with Ta and T1 urothelial carcinoma of the bladder were enrolled in this retrospective study.
• ? The primary endpoint of the present study was recurrence‐free survival, and the median follow‐up duration was 37 months in recurrence‐free survivors.

RESULTS

• ? Multivariate Cox proportional hazards regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), prior recurrence rate, number of tumours and T category were independent predictors of time to recurrence (P < 0.05). According to the EAU guidelines for predicting recurrence, the vast majority of Japanese patients were classified into intermediate risk.
• ? The intermediate‐risk patients were further divided into intermediate‐low‐risk and intermediate‐high‐risk subgroups based on the European Organization for Research and Treatment of Cancer risk table, and a significant difference in the recurrence‐free survival rates was found between these subgroups (P < 0.001).
• ? It was also found that patients with high risk combined with intermediate‐high risk had significantly poorer recurrence‐free survival rates than those with low risk combined with intermediate‐low risk (P < 0.001).

CONCLUSIONS

• ? This is the first report on the ECOG PS as a potentially useful predictor for bladder tumour recurrence.
• ? The risk group stratification of the EAU guidelines for recurrence might not be applicable to Japanese patients with Ta and T1 bladder tumours, but the subgroup classification of intermediate risk could be appropriate.

     

Significant impact of age at diagnosis on the prognosis of Japanese patients with pT1 renal cell carcinoma following surgical resection

Study Type – Prognosis (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Several parameters significantly associated with the prognosis of patients with small venal cell carcinoma (RCC) have been reported; however, the outcomes described in such studies are not totally consistent, and the majority of these studies were based on the data from Western populations. Age of diagnosis is a significant predictor of disease recurrence as well as overall survivals in Japanese patients with pT1 RCC following surgical resection; therefore, intensive follow‐up of older patients is necessary even for those with pT1 RCC.

OBJECTIVE

• ? To retrospectively review oncological outcomes following surgical resection in Japanese patients with pT1 renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? The present study included a total of 832 consecutive Japanese patients who underwent either radical or partial nephrectomy and were subsequently diagnosed as having localized pT1 RCC.
• ? The significance of several clinicopathological factors in their postoperative outcomes was analysed.

RESULTS

• ? The median (range) age of the 832 patients was 66 (31–90) years. Radical and partial nephrectomies were performed for 710 patients (85.3%) and 122 patients (14.7%), respectively. Distribution of pathological stage was pT1a in 582 patients (70.0%) and pT1b in 250 patients (30.0%).
• ? During the observation period (median 44 months, range 3–114 months), postoperative disease recurrence developed in 38 patients (4.6%) and death occurred in 34 (4.1%). The 5‐year recurrence‐free and overall survival rates were 93.6% and 94.1%, respectively.
• ? Of several factors examined, only age at diagnosis was identified as an independent predictor of both postoperative disease recurrence and overall survival in these patients. Furthermore, there were significant differences in the recurrence‐free and overall survivals among patient groups stratified by age at diagnosis.

CONCLUSION

• ? These findings suggest that age at diagnosis is a significant predictor of disease recurrence as well as overall survival in patients with pT1 RCC following surgical resection; therefore, intensive follow‐up of older patients is necessary even for those with pT1 RCC.

     

Local recurrence after tumour enucleation for renal cell carcinoma with no ablation of the tumour bed: results of a prospective single-centre study

Study Type – Therapy (individual cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Tumour enucleation was demonstrated to be an oncologically safe conservative treatment for small renal masses in agreement with the EAU guidelines. Nevertheless, the theoretical increased risk of positive surgical margins and local recurrence, led some authors to hypothesize a possible key role of laser or diathermy ablation of the tumour bed to free the kidney parenchyma from any tumour cells that extended in the kidney parenchyma. Our pathological and clinical results showed that tumour enucleation with no ablation of the tumour bed (e.g. diathermy, argon beam or Nd‐YAG laser) can ensure negative surgical margins and it is not associated with an increased risk of local recurrence.

OBJECTIVE

• ? To prospectively evaluate the risk of positive surgical margins and local recurrence after blunt tumour enucleation (TE) with no ablation of the tumour bed.

PATIENTS AND METHODS

• ? Between 2005 and 2007, data were gathered prospectively from 201 consecutive patients who had open TE with no ablation of the tumour bed.
• ? Overall, 164 consecutive patients had TE for single sporadic renal cell carcinoma (RCC).
• ? All patients had an abdominal computed tomography (CT) at the last follow‐up visit.

RESULTS

• ? The pathological review showed that 70.2% of tumours were pT1a, 18.9% were pT1b, 1.8% were pT2 and 9.1% were pT3a.
• ? The mean (range, interquartile range) tumour greatest dimension was 3.5 (0.5–12.5, 2.4–4.1) cm.
• ? Although no deliberate attempt to resect normal parenchyma was performed, the pathological analysis showed the presence of a thin layer of parenchyma with a mean (range) thickness of 0.97 (0.31–1.60) mm, around the tumour. None of the patients had positive surgical margins.
• ? At a mean (median, range) follow up of 40 (38, 25–62) months, three (1.8%) patients had local recurrence, of whom one (0.6%) had a true local recurrence at the enucleation site detected 35 months after surgery, while two had kidney recurrence elsewhere associated with concurrent systemic metastases diagnosed 16 and 13 months after surgery.

CONCLUSIONS

• ? TE with no ablation of the tumour bed is a safe technique with a local recurrence rate of 0.6%.
• ? The histopathological analysis showed the presence of a minimal tumour‐free surgical margin, although no deliberate attempt to resect normal parenchyma is performed.

     

Treatment changes and long‐term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non‐muscle‐invasive bladder cancer (NMIBC)?

Study Type – Therapy (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? HAL fluorescence cystoscopy is known to improve tumour detection in NMIBC cases and to have a potentially favourable impact concerning the recurrence rates. The present trial assessed the advantages of HAL cystoscopy with regard to postoperative treatment changes and 2 years' recurrence rates, subjects that are poorly evaluated in the literature.

OBJECTIVES

• ? To evaluate in a prospective, randomized study the impact of hexaminolevulinate blue‐light cystoscopy (HAL‐BLC) on the diagnostic accuracy and treatment changes in cases of non‐muscle invasive bladder cancer (NMIBC) compared with standard white‐light cystoscopy (WLC).
• ? To compare the long‐term recurrence rates in the two study arms.

PATIENTS AND METHODS

• ? In all, 362 patients suspected of NMIBC were included in the trial based on positive urinary cytology and/or ultrasonographic suspicion of bladder tumours and underwent transurethral resection of bladder tumours.
• ? A single postoperative mytomicin‐C instillation was performed in all cases, intravesical chemotherapy for intermediate‐risk patients and BCG instillations for high‐risk cases.
• ? The follow‐up protocol consisted of urinary cytology and WLC every 3 months for 2 years.
• ? Only first‐time recurrences after the initial diagnosis were considered.

RESULTS

• ? In the 142 patients with NMIBC in the HAL‐BLC series, tumour detection rates significantly improved for carcinoma in situ, pTa andoverall cases.
• ? In 35.2% of the cases, additional malignant lesions were found by HAL‐BLC and consequently, the recurrence‐ and progression‐risk categories of patients and subsequent treatment improved in 19% of the cases due to fluorescence cystoscopy.
• ? In all, 125 patients in the HAL‐BLC group and 114 of the WLC group completed the follow‐up.
• ? The recurrence rate at 3 months was lower in the HAL‐BLC series (7.2% vs 15.8%) due to fewer ‘other site’ recurrences when compared with the WLC series (0.8% vs 6.1%).
• ? The 1 and 2 years recurrence rates were significantly decreased in the HAL‐BLC group compared with the WLC group (21.6% vs 32.5% and 31.2% vs 45.6%, respectively).

CONCLUSIONS

• ? HAL‐BLC was better than WLC for detecting NMIBC cases and improved tumour detection rates.
• ? HAL‐BLC significantly modified the postoperative treatment of cases.
• ? The 3 months, 1 and 2 years recurrence rates were significantly improved in the HAL‐BLC arm.

     

Does the presence of muscularis propria on transurethral resection of bladder tumour specimens affect the rate of upstaging in cT1 bladder cancer?

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? It is already known and accepted that the presence of mucularis propria (MP) on bladder biopsy is incremental to the clinical staging process for this disease entity. This study establishes that the lack of MP also portends a higher risk of pathologic upstaging at the time of radical cystectomy. OBJECTIVE

• ? To determine how the presence of MP on T1 biopsy specimens affects the outcome of patients undergoing RC as compared to when no MP is identified in the TURBT specimen.

PATIENTS AND METHODS

• ? Patients were retrospectively identified from the Columbia University Urologic Oncology Database.
• ? From January 1986 to October 2009, 114 patients diagnosed with cT1N0M0 bladder cancer who underwent RC within 4 months of their last biopsy were identified.
• ? Patients were stratified based on the presence of MP on T1 biopsy, and upstaging was defined as any tumor T2 or greater, N+, or M+ at the time of radical cystectomy.
• ? The rate of upstaging was assessed using univariate and multivariate regression models; Kaplan meier curves were also extrapolated for each cohort to compare disease specific and overall survival patterns.

RESULTS

• ? Of the 114 patients evaluated in this study, 24 (20.2%) did not have MP on their T1 biopsy before RC. The rate of upstaging (>=pT2) stratified by the presence of MP on biopsy was 50% and 78%, respectively (p = 0.017).
• ? On univariate analysis, lack of MP on biopsy was associated with an increased risk of upstaging (HR 3.52, p = 0.021, CI 1.2–10.3), however did not reach significance as an independent predictor (HR 2.9, p = 0.056, CI 0.97–8.9).
• ? At a mean follow‐up of 33.5 months, there was no difference in disease specific (p = 0.41) and overall survival (p = 0.68) between groups.

CONCLUSIONS

• ? The lack of MP on TURBT for high grade cT1N0M0 bladder cancer portends a high likelihood of upstaging at RC, although this risk did not translate into a detectable increased risk of disease specific mortality.

     

Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

• ? To confirm the recurrence‐preventing efficacy and safety of 18‐month bacillus Calmette‐Guérin (BCG) maintenance therapy for non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

• ? The enrolled patients had been diagnosed with recurrent or multiple non‐muscle‐invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT).
• ? The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once‐weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non‐maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence‐free survival (RFS).

RESULTS

• ? Efficacy analysis was performed for 115 of the full‐analysis‐set population of 116 eligible patients, including 41 maintenance group patients, 42 non‐maintenance group patients and 32 epirubicin group patients.
• ? At the 2‐year median point of the overall actual follow‐up period, the final cumulative RFS rates in the maintenance, non‐maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively.
• ? The RFS following TURBT was significantly prolonged in the maintenance group compared with the non‐maintenance group (generalized Wilcoxon test, P= 0.0190).

CONCLUSION

• ? BCG maintenance therapy significantly prolonged the post‐TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi-institutional study

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Few studies supported the expanded indications for nephron‐sparing surgery (NSS) in selected patients with 4.1 cm renal tumours in the size range (T1b). However, all these comparative studies included both imperative and elective partial nephrectomy and patient selection for analysis was based on pathological stage (pT1) and not on clinical stage (cT1). Patients with clinically organ‐confined RCC (cT1) who are candidates for elective PN have a limited risk of clinical understaging. NSS is not associated with an increased risk of recurrence and cancer‐specific mortality both in cT1a and cT1b tumours

OBJECTIVE

• ? To compare the oncological outcomes of patients who underwent elective partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organ‐confined renal masses ≤7 cm in size (cT1).

PATIENTS AND METHODS

• ? The records of 3480 patients with cT1N0M0 disease were extracted from a multi‐institutional database and analyzed retrospectively.

RESULTS

• ? In patients who underwent PN, the risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases.
• ? With regard to the cT1a patients, the 5‐ and 10‐year cancer‐specific survival (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%, respectively, after PN (log‐rank test: P = 0.01).
• ? With regard to cT1b patients, the 5‐year CSS probabilities were 92.6% after RN and 90% after PN, respectively (log‐rank test: P = 0.89).
• ? Surgical treatment failed to be an independent predictor of CSS on multivariable analysis, both for cT1a and cT1b patients.
• ? Interestingly, PN was oncologically equivalent to RN also in patients with pT3a tumours (log‐rank test: P = 0.91).

CONCLUSIONS

• ? Elective PN is not associated with an increased risk of recurrence and cancer‐specific mortality in both cT1a and cT1b tumours.
• ? Data from the present study strongly support the use of partial nephrectomy in patients with clinically T1 tumours, according to the current recommendations of the international guidelines.

     

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.

     

Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment

Study Type – Therapy (case series)
Level of Evidence 4 What's known on the subject? and What does the study add? Intravesical BCG treatment has been used worldwide for many decades but there are only a few published reports on persisting BCG infection of the urinary bladder. This is the first report on large tuberculosis‐like ulcers of the urinary bladder after intravesical BCG treatment. The finding results in a recommendation to take urine cultures for mycobacteriae in patients with unclear inflammatory lesions in the bladder after instillation of BCG.

OBJECTIVE

• ? To report a late bacille Calmette–Guérin (BCG) complication previously not described in the literature.

PATIENTS AND METHODS

• ? We reviewed our database with 858 patients treated with BCG from 1986 to 2008 and identified 13 male patients (1.8% of all male patients) who had a large tuberculous‐like bladder ulcer.

RESULTS

• ? All patients had high‐grade tumours and seven had tumours invading lamina propria before BCG treatment. A solitary ulceration or inflammatory lesion, 10–50 mm in diameter, was seen at routine follow‐up cystoscopy 2–34 months (median 8 months) after the first instillation. Significantly more patients had been treated with BCG‐RIVM than with BCG‐Tice (10/320 vs. three of 454, P < 0.01). BCG was cultured from urine 3–34 months (median 14 months) after the last instillation.
• ? So far, eight patients have been successfully treated with rifampicin and isoniazid. Nine patients are still tumour‐free 15–66 months (median 44 months) after the last transurethral resection before BCG treatment.
• ? Another three patients had one to two non‐invasive recurrences. One patient had an invasive recurrence and underwent cystectomy. The present study is limited by biases associated with its retrospective design.

CONCLUSIONS

• ? This is the first report on persisting BCG infections with large inflammatory lesions in the bladder. Treatment is effective and the oncological outcome is good.
• ? Mycobacterial cultures of the urine should be performed in BCG‐patients with unclear inflammatory lesions in the bladder since a delayed diagnosis of a persistent BCG infection could result in a permanently reduced bladder capacity.
• ? Large studies are warranted to study differences in efficacy and side‐effects between different BCG strains.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

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

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.

     

Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder

What's known on the subject? and What does the study add? Steroid hormone receptor signals have been implicated in bladder tumourigenesis and tumour progression. The expression of androgen and/or oestrogen receptors has been assessed in bladder cancer, leading to conflicting data of expression levels and their relationship to histopathological characteristics of the tumours. We simultaneously analyze three receptors in non‐neoplastic bladder tissues as well as in primary and metastatic bladder tumour specimens. Our data demonstrate that the expression status correlates with tumour grades/stages and patients’ outcomes.

OBJECTIVE

• ? To assess the expression of the androgen receptor (AR) and oestrogen receptors (ERs) in bladder tumours because recent studies have shown conflicting results and the prognostic significance of their expression remains unclear.

PATIENTS AND METHODS

• ? We investigated the expression of AR, ERα and ERβ in 188 bladder tumour specimens, as well as matched 141 non‐neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry.
• ? We then evaluated the relationships between their expression and the clinicopathological features available for the present patient cohort.

RESULTS

• ? AR/ERα/ERβ was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumours and 71%/64%/71% of metastatic tumours.
• ? Significantly lower expression of AR/ERα was found in high‐grade tumours (36%/23%) and tumours invading muscularis propria (33%/19%) compared to low‐grade tumours (55%; P= 0.0232/38%; P= 0.0483) and tumours not invading muscularis propria (51%; P= 0.0181/35%; P= 0.0139), respectively.
• ? Significantly higher expression of ERβ was found in high‐grade tumours (58%) and tumours invading muscularis propria (67%) compared to low‐grade tumours (29%; P= 0.0002) and tumours not invading muscularis propria (34%; P < 0.0001), respectively.
• ? Kaplan–Meier and log‐rank tests further showed that positivity of ERβ (but not AR or ERα) was associated with the recurrence of low‐grade tumours (P= 0.0072); the progression of low‐grade tumours (P= 0.0005), high‐grade tumours not invading muscularis propria (P= 0.0020) and tumours invading muscularis propria (P= 0.0010); or disease‐specific mortality in patients with tumours invading muscularis propria (P= 0.0073).

CONCLUSIONS

• ? Compared to benign bladders, a significant decrease in the expression of AR, ERα or ERβ in bladder cancer was seen.
• ? Loss of AR or ERα was strongly associated with higher grade/more invasive tumours, whereas ERβ expression was increased in high‐grade/invasive tumours and predicted a worse prognosis.

     

Radical cystectomy for patients with pT4 urothelial carcinoma in a large population‐based study

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Given the natural history of pT4 urothelial carcinoma of the urinary bladder, and the substantially poorer survival of pT4 patients relative to pT3, it may be argued that radical cystectomy is not justified in these patients. Relying on a large population‐based retrospective analysis, the current study identified two main categories of patients with pT4 urothelial carcinoma of the urinary bladder. The first comprised of patients with pT4b disease, whose disease phenotype was clearly more aggressive than their pT3 counterparts. The second group consisted of patients with pT4a disease, whose disease phenotype was very similar to patients with pT3. These findings indicate that patients with pT4b disease should be provided with the maximal amount of therapeutic interventions, such as administration of early adjuvant chemotherapy and perhaps early adjuvant radiotherapy.

OBJECTIVE

• ? To examine cancer‐specific mortality (CSM) in patients with pT4N_0–3M₀ urothelial carcinoma of the urinary bladder (UCUB) and to compare it to patients with pT3N_0–3M₀, in a population‐based cohort treated with radical cystectomy (RC).

PATIENTS AND METHODS

• ? RCs were performed in 5625 pT3‐T4bN_0–3M₀ patients with UCUB within 17 Surveillance, Epidemiology and End Results (SEER) registries between 1988 and 2006.
• ? Univariable and multivariable models tested the effect of pT4a vs pT4b vs pT3 stages on CSM.
• ? Covariates consisted of age, gender, race, lymph node status and SEER registries.
• ? All analyses were repeated in 3635 pN₀ patients.

RESULTS

• ? Of 5625 patients, 2043 (36.3%) had pT4aN_0–3, 248 (4.4%) had pT4bN_0–3 and 3334 had pT3N_0–3 (59.3%) UCUB.
• ? The 5‐year CSM was 57.6% vs 81.7% vs 53.9% for, respectively, pT4aN_0–3 vs pT4bN_0–3 vs pT3N_0–3 patients (all log‐rank P= 0.008).
• ? In multivariable analyses the rate of CSM was 2.3‐fold higher in pT4b vs pT3 (P < 0.001), 1.1‐fold higher in pT4a vs pT3 (P= 0.002) and 2.0‐fold higher in pT4a vs pT4b patients.
• ? After restriction to pN₀ stage, pT4b patients had a 2.3‐fold higher rate of CSM than pT3 patients (P < 0.001) and pT4b patients had a 2.1‐fold higher rate of CSM than pT4a patients (P < 0.001).
• ? The CSM rate was the same for pT4a and pT3 patients (P= 0.1).

CONCLUSIONS

• ? Our findings indicate that patients with pT4a UCUB have similar CSM as those with pT3 UCUB.
• ? Consequently, RC should be given equal consideration in patients with pT3 and pT4a UCUB.

     

Comparison of oncological outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for the management of clear‐cell renal cell carcinoma: a multi‐institutional study

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic radical nephrectomy (LRN) can be performed by a retroperitoneal approach with similar efficacy compared to the transperitoneal approach. However, the oncological acceptance of LRN has been based on studies which have been carried out primarily by transperitoneal approach, and oncological results of the retroperitoneal approach alone are lacking. Our study confirmed that retroperitoneal laparoscopic radical nephrectomy is oncologically‐equivalent to transperitoneal approach in homogeneous group with the final pathological diagnosis of clear cell RCC.

OBJECTIVE

• ? To investigate the oncological efficacy of retroperitoneal laparoscopic radical nephrectomy (RLRN) compared with transperitoneal laparoscopic radical nephrectomy (TLRN) for the management of clear‐cell renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? With emphasis on survival and disease recurrence, a retrospective analysis was made of 580 patients who underwent TLRN (472 patients) or RLRN (108 patients) at 23 institutions between January 1997 and December 2007.
• ? Inclusion criteria were clear‐cell RCC, stage pT1 to pT2 without any nodal involvement, and metastasis.
• ? Overall survival and recurrence‐free survival curves were estimated using the Kaplan–Meier method.
• ? To assess the association between the surgical approach and survival outcomes, Cox proportional hazard models were constructed.

RESULTS

• ? The median follow‐up was 30 months in the TLRN group and 35.6 months in the RLRN group. Both groups were comparable regarding age, gender, body mass index (BMI), Fuhrman’s grade, size of tumours and stage.
• ? Kaplan–Meier curves and the log‐rank test showed no significant difference between the TLRN and RLRN groups in 5‐year overall (92.6% vs 94.5%; P = 0.669) and recurrence‐free survival (92.0% vs 96.2%; P = 0.244).
• ? In a Cox regression model with age, gender, Eastern Cooperative Oncology Group performance status, BMI, nuclear grade and T‐stage adjusted variables, no significant difference was found between the two surgical approaches.

CONCLUSION

• ? The present study is the largest oncological analysis for laparoscopic radical nephrectomy (LRN) comparing transperitoneal and retroperitoneal approaches. The data from it provide the objective evidence to suggest similar oncological outcomes for both approaches to LRN.