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.

     

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.

     

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.

     

Survival after radical cystectomy of non-bilharzial squamous cell carcinoma vs urothelial carcinoma: a competing-risks analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? To date, there is controversy about the impact of histological subtype of bladder cancer (nonbilharzial squanous cell carcinoma vs. urothelial carcinoma) on cancer control outcomes. Our study shows that the histological subtype may have an impact on the stage of bladder cancer at presentation. However, after adjusting to stage, the histological subtype has no impact on cancer control outcomes.

OBJECTIVES

• ? To test the effect of histological subtype (NBSCC vs UC) on cancer‐specific mortality (CSM), after adjusting for other‐cause mortality (OCM).
• ? In Western countries, non‐bilharzial squamous cell carcinoma (NBSCC) is the second most common histological subtype in bladder cancer (BCa) after urothelial carcinoma (UC).

PATIENTS AND METHODS

• ? We identified 12 311 patients who were treated with radical cystectomy (RC) between 1988 and 2006, within 17 Surveillance, Epidemiology and End Results (SEER) registries.
• ? Univariable and multivariable competing‐risks analyses tested the relationship between histological subtype and CSM, after accounting for OCM.
• ? Covariates consisted of age, sex, year of surgery, race, pathological T and N stages, as well as tumour grade.

RESULTS

• ? Histological subtype was NBSCC in 614 (5%) patients vs UC in 11 697 (95%) patients.
• ? At RC, the rate of non‐organ confined (NOC) BCa was higher in NBSCC patients than in their UC counterparts (71.7% vs 52.2%; P < 0.001).
• ? After adjustment for OCM, The 5‐year cumulative CSM rates were 25.0% vs 19.8% (P= 0.2) for patients with NBSCC vs UC organ confined (OC) BCa, respectively. The same rates were 46.3% vs 49.3% in patients with NOC BCa (P= 0.1).
• ? In multivariable competing‐risks analyses, histological subtype (NBSCC vs UC) failed to achieve independent predictor status of CSM in patients with OC (hazard ratio, 1.2; P= 0.06) or NOC BCa (hazard ratio, 1.1; P= 0.1).

CONCLUSIONS

• ? At RC, the rate of NOC BCa is higher in NBSCC patients than in their UC counterparts.
• ? Despite a more advanced stage at surgery, NBSCC histological subtype is not associated with a less favourable CSM than UC histological subtype, after accounting for OCM and the extent of the disease (OC vs NOC).

     

Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pT1 clear-cell renal cell carcinoma

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three‐dimensional tumour volume (cm³) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC‐specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC.

OBJECTIVE

• ? To address whether information on three‐dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone.

PATIENTS AND METHODS

• ? We identified 955 patients treated with radical nephrectomy or nephron‐sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non‐cystic clear‐cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients.
• ? We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis.
• ? Univariate and multivariable associations with RCC‐specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS

• ? Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30–15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83–7.85; P= 0.10).
• ? Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients.
• ? Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC‐specific death were similar.
• ? Multivariable adjustment did not alter our findings.

CONCLUSIONS

• ? Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC.
• ? Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.

     

The value of urinary prostate cancer gene 3 (PCA3) scores in predicting pathological features at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins. These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve‐sparing surgery.

OBJECTIVE

• ? To assess correlations between Prostate CAncer gene 3 (PCA3) levels and pathological features of radical prostatectomy (RP) specimens, which define cancer aggressiveness.

PATIENTS AND METHODS

• ? After digital rectal examination (DRE), first‐catch urine was collected from 160 patients with localized prostate cancer. The PCA3 score was calculated using the Gene Probe Progensa^? assay.
• ? PCA3 scores were then correlated to the pathological features of the RP specimens.

RESULTS

• ? PCA3 scores correlated significantly with tumour volume (r= 0.34, P < 0.01). A PCA3 score of >35 was an independent predictor in a multivariate analysis of a tumour volume >0.5 mL (odds ratio [OR] 2.7, P= 0.04).
• ? It was also an independent predictor of positive surgical margins (OR 2.4, P= 0.04). Receiver–operator characteristic curves indicated PCA3 as the most accurate predictor of positive margins (area under the curve [AUC] 0.62), in addition to a positive biopsy percentage (AUC 0.52).
• ? There was also a significant difference in the mean PCA3 score between Gleason score patient groups (6 vs ≥7) and pathological stage groups (pT0/2 vs pT3/4).

CONCLUSIONS

• ? PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins.
• ? These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve‐sparing surgery.

     

Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non‐muscle‐invasive bladder cancer. Owing to high recurrence and progression rates, a two‐pronged strict surveillance regimen, consisting of both functional and oncological follow‐up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node‐positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi‐institutional project lends further support to the continued use of risk‐stratified follow‐up and emphasizes the need for earlier strict surveillance in patients with extravesical and node‐positive disease.

OBJECTIVES

• ? To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC).
• ? To establish appropriate surveillance protocols.

PATIENTS AND METHODS

• ? We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres.
• ? Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study.

RESULTS

• ? A total of 825 patients (43.6%) developed recurrence.
• ? According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant.
• ? The median (range) time to recurrence for the entire population was 10.1 (1–192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively.
• ? According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5‐yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1–72 months) than ≥pT3N0 tumours (10 months, range 1–70 months) or ≤pT2N0 tumours (14 months, range 1–192 months, P < 0.001).

CONCLUSIONS

• ? Differences in recurrence patterns after RC suggest the need for varied follow‐up protocols for each group.
• ? We propose a stage‐based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over‐investigation.

     

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.

     

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Nerve sparing radical prostatectomy has been associated with increased risk of positive surgical margins due to the close anatomical relationship of the neurovascular bundle to the posterolateral aspect of the prostatic fascia. Our study of 945 men who underwent radical prostatectomy be one experienced surgeon found no increased risk of positive surgical margins, whether the cancer was organ confined or extracapsular extension was present.

OBJECTIVE

• ? To examine whether nerve‐sparing surgery (NSS) is a risk factor for positive surgical margins (PSMs) in patients with either organ‐confined prostate cancer or extracapsular extension (ECE).

PATIENTS AND METHODS

• ? Clinicopathological outcome data on 945 consecutive patients treated with radical prostatectomy (RP) were prospectively collected.
• ? All patients underwent RP (bilateral, unilateral or non‐NSS) by one surgeon between 2002 and 2007.
• ? Risk of PSMs and their locations with respect to NSS was determined by multivariate logistic regression analysis adjusting for preoperative risk factors for PSMs within pT2, pT3a and pT3b tumours.

RESULTS

• ? Overall a PSM was identified in 19.6% of patients in an unscreened population with mean prostate‐specific antigen (PSA) level of 8.1 ng/mL.
• ? There was no significant difference in rates of PSMs between NSS groups on multivariate analysis (P= 0.147).
• ? There was no significant difference in pT2 (P= 0.880), pT3a (P= 0.175) or pT3b (P= 0.354) tumours.
• ? The only significant predictor of PSMs was preoperative PSA level (risk ratio 1.289, P= 0.006).
• ? There was no significant difference in the location of PSMs except for the pT3a group, where the patients that had bilateral NSS were at higher risk of a posterolateral PSM (P= 0.028).

CONCLUSIONS

• ? With appropriate selection of patients, NSS does not increase the risk of PSMs, whether the cancer is organ confined or ECE is present.
• ? The adverse impact of the NSS procedure in the hands of an experienced surgeon is minimal and is a realistic compromise to obtain the increase in health‐related quality of life offered by NSS.

     

Train hard and well but train intelligently: a comment on 'Operative experience of urological trainees in the UK'

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Married individuals have lower morbidity and mortality rates for all major causes of death. Cancer‐specific survival is better in married patients with testis cancer, prostate cancer, breast cancer, cervical cancer, as well as head and neck cancers. We have found the effect of marital status on outcomes after radical cystectomy to be variable, depending on gender and the outcome addressed. Being married is predictive of lower all‐cause mortality for both men and women relative to their separated, divorced or widowed (SDW) or never‐married counterparts. It is also predictive of lower bladder‐cancer‐specific mortality relative to SDW individuals. Marriage also exerts a protective effect on men regarding non‐organ‐confined disease, with those never having married having significantly higher rates.

OBJECTIVES

• ? To examine the effect of marital status (MS) on the rate of non‐organ‐confined disease (NOCD) at radical cystectomy (RC)
• ? To assess the effect of MS on the rate of bladder‐cancer‐specific mortality (BCSM) and all‐cause mortality (ACM) after RC for urothelial carcinoma of the urinary bladder (UCUB).

MATERIALS AND METHODS

• ? A total of 14 859 patients, who underwent RC for UCUB, were captured within the Surveillance, Epidemiology, and End Results database, between 1988 and 2006.
• ? Logistic regression analysis was used to assess the rate of NOCD (T_3‐4/N_I‐3/M₀) at RC and Cox regression analyses were used to assess BCSM and ACM.
• ? Analyses were stratified according to gender; covariates included socio‐economic status, tumour stage, age, race, tumour grade and year of surgery.

RESULTS

• ? Never‐married males had a higher rate of NOCD at RC (odds ratio = 1.22, P= 0.004), an effect not found in never‐married females.
• ? Separated, divorced or widowed (SDW) males (hazard ratio [HR]= 1.18, P= 0.005) and females (HR = 1.16, P= 0.002) had higher rates of BCSM than their married counterparts.
• ? SDW and never‐married males had higher rates of ACM than their married counterparts (HR = 1.22, P < 0.001 and HR = 1.26, P < 0.001, respectively).
• ? SDW and never‐married females also had higher rates of ACM than married females (HR = 1.24, P < 0.001 and HR = 1.22, P= 0.01, respectively).

CONCLUSIONS

• ? For both men and women, being SDW conveyed an increased risk of BCSM after RC.
• ? SDW and never marrying had a deleterious effect on ACM.
• ? Unfavourable stage at RC was also seen more commonly in never‐married males.

     

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.

     

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.

     

Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

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

OBJECTIVE

• ? To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well‐studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS

• ? A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution.
• ? The results were classified into two groups based on the total serum testosterone: group1, <3 ng/mL; group 2, ≥3 ng/mL.
• ? Student’s t‐test was used to compare continuous variables, and Fisher’s exact test or the chi‐squared test was used to compare categorical variables.
• ? Survival curves were established using the Kaplan–Meier method and compared using the log‐rank test. In all tests, P < 0.05 was considered to indicate statistical significance.

RESULTS

• ? All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co‐morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels.
• ? In pathological specimens, low total testosterone (<3 ng/mL) was an independent risk factor for high Gleason score (>7) and for locally advanced pathological stage (pT3 and pT4).
• ? Higher preoperative testosterone correlated with disease confined to the gland.
• ? There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other.

CONCLUSION

• ? Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

     

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.

     

Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer

Study Type – Prognosis (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? PSA screening reduces prostate cancer mortality but also may lead to unnecessary biopsies and overdiagnosis of insignificant tumours. PSA velocity (PSAV) risk count (number of serial PSAV exceeding 0.4 ng/ml/year) significantly improves the performance characteristics of screening for overall prostate cancer and high‐grade disease on biopsy. Risk count may be useful to reduce unnecessary biopsies and prostate cancer overdiagnosis compared to PSA alone.

OBJECTIVE

• ? To determine whether the prostate‐specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life‐threatening tumours.

PATIENTS AND METHODS

• ? From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening‐study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer.
• ? The PSAV risk count was determined as the number of PSAV measurements of >0.4 ng/mL/year (0, 1, or 2).
• ? We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen‐detected and high‐grade prostate cancer.

RESULTS

• ? The PSAV was >0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001).
• ? After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2‐fold increased risk of prostate cancer (95% confidence interval 7.0–9.6, P < 0.001) and 5.4‐fold increased risk of Gleason score 8–10 prostate cancer on biopsy.
• ? Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P= 0.031) and reclassified individuals for the risk of high‐grade prostate cancer (net reclassification, P < 0.001).

CONCLUSIONS

• ? Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high‐grade disease.
• ? Compared with men with a risk count of ≤1, those with two PSAV measurements of >0.4 ng/mL/year (risk count 2) had an 8‐fold increased risk of prostate cancer and 5.4‐fold increased risk of Gleason 8–10 disease on biopsy, adjusting for age and PSA level.
• ? Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low‐risk prostate cancer.

     

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.

     

Robot-assisted nerve-sparing radical cystectomy with bilateral extended pelvic lymph node dissection (PLND) and intracorporeal urinary diversion for bladder cancer: initial experience in 27 cases

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Robot‐assisted (RA) procedures are increasingly being performed as minimally invasive surgical approaches. RA radical cystectomy (RARC) has the advantages of decreased blood loss, decreased time to flatus, decreased time to bowel movement and decreased analgesic use compared with open RC. Positive surgical margin rates and lymph node yields are similar to open RC. RARC was suggested to have the advantage of having fewer complications compared with open RC. To date, very few authors have reported their experience with totally intracorporeal RARC including the urinary diversion. This case series of totally intracorporeal RARC including the urinary diversion reports the operative and postoperative variables, pathological variables, complications, oncological outcomes, functional outcomes and the feasibility of these complex procedures. Advantages of using the surgical robot enable the console surgeon to preserve the neurovascular bundles with excellent surgical oncological safety. Outcomes of the present series suggest that RARC seems to have excellent short‐term surgical and pathological outcomes and satisfactory functional results. Additionally, performing the whole procedure totally intracorporeally might lead to decreased insensible fluid loss from the bowels, which might also prevent development of electrolyte imbalance resulting in earlier bowel function recovery. Additional advantages of this approach include decreased wound infection and dehiscence, better wound healing and better cosmesis.

OBJECTIVE

• ? To report the outcomes of 27 patients whom we performed robot‐assisted radical cystoprostatectomy and cystectomy (RARC) with intracorporeal urinary diversion (Studer pouch and ileal conduit) for bladder cancer.

PATIENTS AND METHODS

• ? Between December 2009 and December 2010, we performed RARC in 25 men (intrafascial bilateral [22], unilateral [one], non‐neurovascular bundle [NVB] sparing [two]), NVB‐sparing RARC with anterior pelvic exenteration in two women, bilateral extended robot‐assisted pelvic lymph node dissection (RAPLND) (25), intracorporeal Studer pouch (23), ileal conduit (two), and extracorporeal Studer pouch (two) construction.
• ? Patient demographics, operative and postoperative variables, pathological variables, complications (according to modified Clavien system) and functional outcomes were evaluated.

RESULTS

• ? The mean (sd , range) operative duration, intraoperative estimated blood loss and mean lymph node (LN) yield were 9.9 (1.4, 7.1–12.4) h, 429 (257, 100–1200) mL and 24.8 (9.2, 8–46), respectively.
• ? The mean (sd , range) hospital stay was 10.5 (6.8, 7–36) days, there was one perioperative death (3.7%), lodge drains were removed at a mean of 11.3 (5.6, 9–35) days and surgical margins were negative in all but one patient who had pT4b disease.
• ? The postoperative pathological stages were: pT0 (five), pTis (one), pT1 (one), pT2a (five), pT2b (three), pT3a (six), pT3b (two), pT4a (three) and pT4b (one).
• ? Positive LNs and incidental prostate cancer were detected in six and nine patients, respectively and at a mean follow‐up of 6.3 (2.9, 1.8–11.3) months, three patients died from metastatic disease and one from cardiac disease.
• ? According to the modified Clavien system, there were nine minor (Grade 1 and 2) and four major (Grade 3–5) complications in the perioperative (0–30 days) period; four minor and three major complications in the postoperative (31–90 days) period. Of the available 18 patients, 11 were fully continent, four had mild and two had severe day‐time incontinence.

CONCLUSIONS

• ? Bilateral NVB‐sparing RARC with RAPLND and intracorporeal Studer pouch or ileal conduit reconstruction are complex procedures with acceptable morbidity, excellent short‐term surgical and pathological outcomes and satisfactory functional results.
• ? Studies with more patients and longer follow‐ups are required to evaluate the feasibility of these RA totally intracorporeal complex procedures.

     

Survival after partial and radical nephrectomy for the treatment of stage T1bN0M0 renal cell carcinoma (RCC) in the USA: a propensity scoring approach

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Partial nephrectomy has become the standard of care for T1a renal tumours, and the application of nephron‐sparing techniques has increasingly been expanded to patients with localized T1b cancers. However, the relative efficacy of partial versus radical nephrectomy for these medium‐sized tumours has yet to be definitively established. This study employs a propensity scoring approach within a large US population‐based cohort to determine that no survival differences exist among patients with T1b renal tumours undergoing partial versus radical nephrectomy.

OBJECTIVES

• ? To compare survival after partial nephrectomy (PN) vs radical nephrectomy (RN) among patients with stage TIb renal cell carcinoma (RCC) using a propensity scoring approach.
• ? Propensity score analysis is a statistical methodology that controls for non‐random assignment of patients in observational studies.

PATIENTS AND METHODS

• ? Using the Surveillance, Epidemiology, and End Results registry, 11 256 cases of RCCs of 4–7 cm that underwent PN or RN between 1998 and 2007 were identified.
• ? Propensity score analysis was used to adjust for potential differences in baseline characteristics between patients in the two treatment groups.
• ? Overall survival (OS) and cancer‐specific survival (CSS) of patients undergoing PN vs RN was compared in stratified and adjusted analysis, controlling for propensity scores.

RESULTS

• ? In all, 1047 (9.3%) patients underwent PN. For the entire cohort, no difference in survival was found in patients treated with PN as compared with RN, as shown by the adjusted hazard ratio (HR) for OS (1.10; 95% confidence interval [CI]: 0.91–1.36) and renal‐CSS (HR 0.91; 95% CI: 0.65–1.27).
• ? When the cohort was stratified by tumour size and age, no difference in survival was identified between the groups.

CONCLUSIONS

• ? Even when stratified by tumour size and age, a survival difference between PN and RN in a propensity‐adjusted cohort of patients with T1b RCC could not be confirmed.
• ? If validated in prospective studies, PN may become the preferred treatment for T1b renal tumours in centres experienced with nephron‐sparing surgery.

     

'Zero ischaemia', sutureless laparoscopic partial nephrectomy for renal tumours with a low nephrometry score

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Ischaemic injury produced by hilar clamping during partial nephrectomy is the main determinant of renal function loss. The exact measurement of ipsilateral renal function loss can be underestimated by serum creatinine levels and estimated GFR. Few reports of unclamped laparoscopic partial nephrectomy (LPN) are available in the literature, although this technique shows promising results. The present study includes a series of patients with the longest follow‐up of LPN without hilar clamping and without parenchymal reconstruction. Excellent cancer control and optimum renal functional preservation suggest that this technique could be performed in selected patients, i.e. those with small and peripheral tumours (also classified as low nephrometry score tumours).

OBJECTIVE

• ? To describe the technique and report the results of ‘zero ischaemia’, sutureless laparoscopic partial nephrectomy (LPN) for renal tumours with a low nephrometry score.

PATIENTS AND METHODS

• ? Between August 2003 and January 2010, data from 101 consecutive patients who underwent ‘zero ischaemia’, sutureless LPN were collected in a prospectively maintained database.
• ? Inclusion criteria were tumour size ≤4 cm, predominant exophytic growth and intraparenchymal depth ≤1.5 cm, with a minimum distance of 5 mm from the urinary collecting system.
• ? Hilar vessels were not isolated, tumour dissection was performed with 10‐mm LigaSure^TM (Covidien, Boulder, CO, USA) and haemostasis was performed with coagulation and biological haemostatic agents without reconstructing the renal parenchyma.
• ? Clinical, perioperative and follow‐up data were collected prospectively, and modifications of functional outcome variables were analysed using the paired Wilcoxon test.

RESULTS

• ? The median (range) tumour size was 2.4 (1.5–4) cm, and the median (range) intraparenchymal depth was 0.7 (0.4–1.4) cm.
• ? Hilar clamping was not necessary in any patient, and suture was performed in four patients to ensure complete haemostasis. The median (range) operation duration was 60 (45–160) min, and median (range) intraoperative blood loss was 100 (20–240) mL.
• ? Postoperative complications included fever (n= 4), low urinary output (n= 3) and haematoma, which was treated conservatively (n= 2). The median (range) hospital stay was 3 (2–5) days. The pathologist reported 30 benign tumours and renal cell carcinoma in 71 cases (pT1a in 69 patients, and pT1b in two patients).
• ? At a median follow‐up of 57 months, one patient underwent radical nephrectomy for ipsilateral recurrence. The 1‐year median (range) decrease of split renal function at renal scintigraphy was 1 (0–5) %.

CONCLUSIONS

• ? Zero ischaemia LPN is a reasonable approach to treating small and peripheral tumours, and a sutureless procedure is feasible in most cases.
• ? This technique has a low complication rate and provides excellent functional outcome without impairing oncological results.

     

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.