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.

     

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).

     

EXTENDING THE INDICATIONS AND ANATOMICAL LIMITS OF PELVIC LYMPH NODE DISSECTION FOR PROSTATE CANCER: IMPROVED STAGING OR INCREASED MORBIDITY?

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

OBJECTIVE

• ? To assess, in a risk/benefit analysis, the additional risk for complications and benefits of extending the indications and anatomical limits of pelvic lymph node dissection (PLND).

PATIENTS AND METHODS

• ? In total, 971 consecutive patients with clinically localized prostate cancer underwent laparoscopic radical prostatectomy from 2003–2007.
• ? Before 1 February 2005, patients with a nomogram probability of lymph node invasion (LNI) <2% did not undergo PLND (No PLND group), whereas those with a LNI ≥2% had a PLND limited to the external iliac nodal group (limited PLND group).
• ? After 1 February 2005, all patients underwent a standard PLND including the external iliac, hypogastric and obturator fossa nodal groups (standard PLND group).
• ? The risk parameters were PLND‐related complications and operating time. Complications were graded using a modified Clavien classification. The benefit was the detection of nodal metastases.

RESULTS

• ? In the subgroup of patients with a LNI ≥2%, standard PLND was a superior operation than the limited PLND in detecting nodal metastases (14.3% vs 4.5%, respectively; P = 0.003).
• ? The risk/benefit of standard vs limited PLND would be one additional grade 3 complication per 20 additional patients with nodal metastases. In the subgroup of patients with LNI <2%, three patients (1.0%) had positive nodes after a standard PLND.
• ? The risk/benefit of standard PLND vs no PLND would be one additional grade 3 complication per three or four additional patients with nodal metastasis. The no PLND group was associated with the lowest risk of grade 1, 2 and 3 complications compared to either the limited or standard PLND groups (P < 0.001).

CONCLUSIONS

• ? In patients with LNI ≥2%, standard PLND detects more nodal metastasis. PLND is associated with higher but non‐prohibitive complications rate.
• ? The present study found no evidence that the incidence of complications would be reduced by a limited PLND.

     

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.

     

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.

     

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.

     

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.

     

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.

     

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.

     

Contemporary trends of in-hospital complications and mortality for radical cystectomy

Study Type – Therapy (trend analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Radical cystectomy (RC) carries significant risks of morbidity and mortality. Little is known whether in‐hospital outcomes are improving for RC. Using a contemporary population‐based cohort, the present study suggests minimal improvement in postoperative complications and mortality overall or by hospital‐volume category from 2001 to 2008. About 29% and 2% of patients undergoing RC will experience a postoperative complication or die during hospitalisation, respectively.

OBJECTIVE

• ? To characterise the contemporary trends of in‐hospital complications and mortality for radical cystectomy (RC) from a contemporary population‐based cohort, as patients undergoing RC for bladder cancer are at significant risk for complications and mortality and the degree to which in‐hospital outcomes have changed over time is unknown.

PATIENTS AND METHODS

• ? We identified 50 625 individuals who underwent RC for bladder cancer between 2001 and 2008 from the Nationwide Inpatient Sample.
• ? Multivariable regression models were used to identify hospital and patient covariates associated with in‐hospital complications and mortality and to estimate predicted probabilities of each outcome.
• ? Temporal trends of in‐hospital mortality and complications were assessed by Wilcoxon rank‐sum test.

RESULTS

• ? The proportion of patients with in‐hospital complications remained stable at 28.3% in 2001–2002 compared with 28.0% in 2007–2008 (P= 0.81 for trend).
• ? In‐hospital mortality was also unchanged from 2.4% in 2001–2002 compared with 2.3% in 2007–2008 (P= 0.87 for trend).
• ? While high‐volume hospitals were associated with lower odds of in‐hospital complications (odds ratio [OR] 0.77, P= 0.01) and mortality (OR 0.60, P= 0.02) compared with low‐volume hospitals, the predicted probabilities of in‐hospital complications or mortality were unchanged within each volume category between 2001 and 2008.

CONCLUSIONS

• ? In‐hospital complications and mortality for RC remain unchanged from 2001 to 2008.
• ? While high‐volume hospitals continue to have better outcomes, there is little evidence that postoperative mortality and morbidity are improving among low‐, medium‐ and high‐volume hospitals.
• ? Increased attention is needed to identify the modifiable aspects of postoperative care to improve in‐hospital outcomes and safety for patients undergoing RC.

     

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.

     

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.

     

Compliance with biopsy recommendations of a prostate cancer risk calculator

Study Type – Diagnostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? So far, few publications have shown that a prediction model influences the behaviour of both physicians and patients. To our knowledge, it was unknown whether urologists and patients are compliant with the recommendations of a prostate cancer risk calculator and their reasons for non‐compliance. Recommendations of the European Randomized study of Screening for Prostate Cancer risk calculator (ERSPC RC) about the need of a prostate biopsy were followed in most patients. In most cases of non‐compliance with ‘no biopsy’ recommendations, a PSA level ≥3 ng/mL was decisive to opt for biopsy. Before implementation of the ERSPC RC in urological practices at a large scale, it is important to obtain insight into the use of guidelines that might counteract the adoption of the use of the RC as a result of opposing recommendations.

OBJECTIVES

• ? To assess both urologist and patient compliance with a ‘no biopsy’ or ‘biopsy’ recommendation of the European Randomized study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC), as well as their reasons for non‐compliance.
• ? To assess determinants of patient compliance.

PATIENTS AND METHODS

• ? The ERSPC RC calculates the probability on a positive sextant prostate biopsy (P_posb) using serum prostate‐specific antigen (PSA) level, outcomes of digital rectal examination and transrectal ultrasonography, and ultrasonographically assessed prostate volume. A biopsy was recommended if P_posb≥20%.
• ? Between 2008 and 2011, eight urologists from five Dutch hospitals included 443 patients (aged 55–75 years) after a PSA test with no previous biopsy.
• ? Urologists calculated the P_posb using the RC in the presence of patients and completed a questionnaire about compliance.
• ? Patients completed a questionnaire about prostate cancer knowledge, attitude towards prostate biopsy, self‐rated health (12‐Item Short Form Health Survey), anxiety (State Trait Anxiety Inventory‐6, Memorial Anxiety Scale for Prostate Cancer) and decision‐making measures (Decisional Conflict Scale).

RESULTS

• ? Both urologists and patients complied with the RC recommendation in 368 of 443 (83%) cases.
• ? If a biopsy was recommended, almost all patients (96%; 257/269) complied, although 63 of the 174 (36%) patients were biopsied against the recommendation of the RC.
• ? Compliers with a ‘no biopsy’ recommendation had a lower mean P_posb than non‐compliers (9% vs 14%; P < 0.001).
• ? Urologists opted for biopsies against the recommendations of the RC because of an elevated PSA level (≥3 ng/mL) (78%; 49/63) and patients because they wanted certainty (60%; 38/63).

CONCLUSIONS

• ? Recommendations of the ERSPC RC on prostate biopsy were followed in most patients.
• ? The RC hence may be a promising tool for supporting clinical decision‐making.

     

Selecting men diagnosed with prostate cancer for active surveillance using a risk calculator: a prospective impact study

Study Type – Prognosis (cohort series) Level of Evidence 2a What's known on the subject? and What does the study add? The present study is one of the first to investigate urologists' and patients' compliance with recommendations based on a risk calculator that calculates the probability of indolent prostate cancer. A threshold was set for a recommendation of active surveillance vs active treatment. Active surveillance recommendations based on a prostate cancer risk calculator were followed by most patients, but 30% with active treatment recommendations chose active surveillance instead. This indicates that the threshold may be too high for urologists and patients.

OBJECTIVES

• ? To assess urologists' and patients' compliance with treatment recommendations based on a prostate cancer risk calculator (RC) and the reasons for non‐compliance.
• ? To assess the difference between patients who were compliant and non‐compliant with recommendations based on this RC.

PATIENTS AND METHODS

• ? Eight urologists from five Dutch hospitals included 240 patients with prostate cancer (PCa), aged 55–75 years, from December 2008 to February 2011.
• ? The urologists used the European Randomized Study of Screening for Prostate Cancer RC which predicts the probability of potentially indolent PCa (P[indolent]), using serum prostate‐specific antigen (PSA), prostate volume and pathological findings on biopsy.
• ? Inclusion criteria were PSA <20 ng/mL, clinical stage T1 or T2a–c disease, <50% positive sextant biopsy cores, ≤20 mm cancer tissue, ≥40 mm benign tissue and Gleason ≤3 + 3. If the P(indolent) was >70%, active surveillance (AS) was recommended, and active treatment (AT) otherwise.
• ? After the treatment decision, patients completed a questionnaire about their treatment choice, related (dis)advantages, and validated measurements of other factors, e.g. anxiety.

RESULTS

• ? Most patients (45/55, 82%) were compliant with an AS recommendation. Another 54 chose AS despite an AT recommendation (54/185, 29%).
• ? The most common reason for non‐compliance with AT recommendations by urologists was the patient's preference for AS (n= 30). These patients most often reported the delay of physical side effects of AT as the main advantage (n= 19).
• ? Those who complied with AT recommendations had higher mean PSA levels (8 vs 7 ng/mL, P= 0.02), higher mean amount of cancer tissue (7 vs 3 mm, P < 0.001), lower mean P(indolent) (36% vs 55%, P < 0.001), and higher mean generic anxiety scores (42 vs 38, P= 0.03) than those who did not comply.

CONCLUSIONS

• ? AS recommendations were followed by most patients, while 29% with AT recommendations chose AS instead.
• ? Although further research is needed to validate the RC threshold, the current version is already useful in treatment decision‐making in men with localized PCa.

     

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.

     

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.

     

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.

     

Contrast-enhanced ultrasonography with contrast-tuned imaging technology for the detection of prostate cancer: comparison with conventional ultrasonography

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The present study was to perform contrast‐tuned imaging (CnTI) technology to detect prostate cancer and compare the use of CnTI technology for the detection of prostate cancer with conventional ultrasonography. The preliminary data from our study suggested that targeted biopsy of the prostate with CnTI technology could improve the cancer detection and detect higher grade prostate cancers.

OBJECTIVES

• ? To perform contrast‐enhanced ultrasonography (CEUS) using contrast‐tuned imaging (CnTI) technology to detect prostate cancer.
• ? To evaluate the detection of prostate cancer with CnTI compared with conventional grey‐scale and power Doppler ultrasonography.

PAIENTS AND METHODS

• ? In all, 150 patients referred for prostate biopsy were evaluated using transrectal grey‐scale, power Doppler and CnTI ultrasonography.
• ? Biopsy was performed at 10 sites in each patient. If an abnormality was found at any of these three ultrasonography examinations, a biopsy specimen was targeted towards from the corresponding site.
• ? The performances of the three ultrasonography techniques for prostate cancer detection were compared.

RESULTS

• ? Prostate cancer was detected at 383 sites from 73 patients. The combination of these three examinations detected more patients with prostate cancer than grey‐scale (P= 0.002), power Doppler (P= 0.001) or baseline imaging (the combination of grey‐scale and power Doppler; P= 0.031) alone.
• ? By biopsy site, CnTI had higher sensitivity and accuracy (73.1% and 83.7%) than grey‐scale (50.9%; P < 0.001 and 78.8%; P < 0.001) or power Doppler (48.3%; P < 0.001 and 77.7%; P < 0.001), while the specificity was similar for grey‐scale (88.4%), power Doppler (87.8%) and CnTI (87.3%; P > 0.05 in each case). CnTI had higher sensitivity (73.1% vs 62.9%; P < 0.001), specificity (87.3% vs 82.1%; P < 0.001) and accuracy (83.7% vs 77.2%; P < 0.001) than baseline imaging.
• ? The mean Gleason score of CnTI‐positive cases was significantly higher than CnTI‐negative cases (7.1 vs 6.3; P= 0.002).

CONCLUSIONS

• ? CEUS using CnTI technology enables a visualization of the microvasculature associated with prostate cancer.
• ? CnTI technology could be used to guide biopsy and improve the detection rate of prostate cancer.
• ? CnTI technology was able to detect higher grade prostate cancers.

     

Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long‐term androgen‐deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long‐term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate‐term follow‐up of a large series of men treatment with RP for cT3 prostate cancer. We report long‐term follow‐up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long‐term follow‐up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone.

OBJECTIVE

• ? To present long‐term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated.

PATIENTS AND METHODS

• ? We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997.
• ? Survival was estimated using the Kaplan–Meier method.
• ? Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome

RESULTS

• ? The median (range) postoperative follow‐up was 14.3 (0.1–23.5) years.
• ? Down‐staging to pT2 disease occurred in 26% (223/843) at surgery.
• ? Local recurrence‐free, systemic progression‐free and cancer‐specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years.
• ? On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P= 0.01), non‐diploid chromatin content (HR 1.8; P= 0.01), positive surgical margins (HR 2.1; P= 0.007), and seminal vesicle invasion (HR 2.1; P= 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer‐specific mortality (HR 0.88; P= 0.01)

CONCLUSIONS

• ? RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow‐up presented here.
• ? RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours.

     

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Pelvic lymph‐node dissection during radical prostatectomy for prostate cancer is certainly a fundamental staging procedure but its therapeutic role is yet under debate. This retrospective study suggests that, in patients with intermediate‐ and high‐risk of prostate cancer, the greater the number of lymph‐nodes removed, the lower the risk of biochemical relapse, even in the presence of 1 or 2 lymph‐node metastasis. However, the Will Rogers phenomenon must be considered due to the retrospective nature of the present study.

OBJECTIVE

• ? To assess the impact of pelvic lymph node dissection (PLND) and of the number of lymph nodes (LNs) retrieved during radical prostatectomy (RP) on biochemical relapse (BCR) in pNX/0/1 patients with prostate cancer according to the clinical risk of lymph node invasion (LNI).

PATIENTS AND METHODS

• ? We evaluated 872 pT2‐4 NX/0/1 consecutive patients submitted to RP between October 1995 and June 2009, with the following inclusion criteria: (i) a follow‐up period ≥12 months; (ii) the avoidance of neoadjuvant hormonal therapy or adjuvant hormonal and/or adjuvant radiotherapy; (iii) the availability of complete follow‐up data; (iv) no pathological T0 disease; (v) complete data regarding the clinical stage and Gleason score (Gs), the preoperative prostate‐specific antigen (PSA) level and the pathological stage.
• ? The patients were stratified as having low risk (cT1a‐T2a and cGs ≤6 and PSA level < 10 ng/mL), intermediate risk (cT2b‐T2c or cGs = 7 or PSA level = 10–19.9) or high risk of LNI (cT3 or cGs = 8–10 or PSA level ≥ 20).
• ? The 872 patients were divided into two LN groups according to the number of LNs retrieved: group 1 had no LN or one to nine LNs removed; group 2 had 10 or more LNs.
• ? The variables analysed were LN group, age, PSA level, clinical and pathological stage and Gs, surgical margin status, LN status and number of LN metastases; the primary endpoint was the BCR‐free survival.

RESULTS

• ? The mean follow‐up was 55.8 months.
• ? Of all the patients, 305 (35%) were pNx and 567 (65.0%) were pN0/1.
• ? Of the 567 patients submitted to PLND, the mean number of LNs obtained was 10.9, and 49 (8.6%) were pN1.
• ? In the 402 patients at low risk of LNI, LN group was not a significant predictor of BCR at univariate analysis, while in the 470 patients at intermediate and high risk of LNI, patients with ≥10 LNs removed had a significantly lower BCR‐free survival at univariate and multivariate analysis.

CONCLUSION

• ? In our study population, a more extensive PLND positively affects the BCR‐free survival regardless of the nodal status in intermediate‐ and high‐risk prostate cancer.