Comparison of the rate, location and size of positive surgical margins after laparoscopic and robot-assisted laparoscopic radical prostatectomy

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

OBJECTIVE

• ? To review and compare the rate, location and size of positive surgical margins (PSMs) after pure laparoscopic radical prostatectomy (LRP) and robot‐assisted laparoscopic radical prostatectomy (RALP).

PATIENTS AND METHODS

• ? The study comprised 200 patients who underwent RALP and 200 patients who underwent LRP up to January 2008.
• ? We compared patient age, body mass index, preoperative prostate‐specific antigen (PSA), preoperative stage and grade, prostate size, pathological stage and grade and neurovascular bundle preservation, as well as PSM rate, size and location.
• ? Continuous and categorical data were compared using Student’s t‐test and Pearson’s chi‐squared test.
• ? Multivariate regression analyses were used to identify preoperative and intraoperative predictors of PSMs.

RESULTS

• ? Although the PSM rate was similar between the two groups (LRP: 12% vs RALP: 13.5%; P= 0.76), location and size were not. PSMs after LRP were mostly at the apex (58.3%; P= 0.038), while most PSMs after RALP were posterolateral ([PL] 48%; P= 0.046).
• ? In addition, the median margin size after RALP was significantly smaller than after LRP (RALP: 2 mm vs LRP: 3.5 mm; P= 0.041).
• ? In univariate and multivariate analyses, tumour‐node‐metastasis (TNM) stage and preoperative PSA were the only independent preoperative predictors of PSMs (P= 0.044 and P= 0.01, respectively).

CONCLUSION

• ? The PSM risk is dependent on TNM stage and preoperative PSA and not the surgical technique, when comparing LRP with RALP.

     

Positive surgical margins are a risk factor for significant biochemical recurrence only in intermediate-risk disease

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Positive surgical margins (PSMs) after radical prostatectomy are common, although their impact on the risk of disease recurrence is unknown. We examined the impact of PSMs on the risk of ‘significant’ biochemical recurrence stratified by their risk of occult metastatic disease. We find that only in intermediate‐risk disease does the presence of a PSM have a significant impact on the risk of recurrence, and this represents a failure of technique. By contrast, for high‐ and low‐risk disease, the risk of recurrence is driven by intrinsic tumour biology, and the presence of a PSM has little impact on outcome.

OBJECTIVE

• ? To determine the impact of surgical margin status on the risk of significant biochemical recurrence (prostate‐specific antigen [PSA] doubling time <3, <6 or <9 months) after prostatectomy.

MATERIALS AND METHODS

• ? Patients undergoing radical prostatectomy with complete clinical and pathological data and detailed PSA follow‐up were identified from two prospectively recorded databases.
• ? Patients were stratified according to their risk of occult systemic disease (low risk: PSA < 10 ng/dL, pT2 stage and Gleason score ≤6; intermediate risk: PSA 10–20 ng/dL, pT2 stage and/or Gleason score 7; high: PSA > 20 ng/dL or pT3‐4 stage or Gleason score 8–10) and the impact of a positive surgical margin (PSM) within each stratum determined by univariable and multivariable analysis.

RESULTS

• ? Of 1514 patients identified, 276 (18.2%), 761 (50.3%) and 477 (31.5%) were classified as having low‐, intermediate‐ and high‐risk disease respectively.
• ? A total of 370 (24.4%) patients had a PSM and with a median follow‐up of 22.2 months, and 165 (7%) patients had a biochemical recurrence.
• ? Sufficient PSA data was available to calculate PSA doubling times in 151/165 patients (91.5%).
• ? The PSM rate rose significantly, from 11% in low‐risk to 43% in high‐risk disease (P < 0.001), with similar positive associations noted with tumour grade, stage and serum PSA (P < 0.001).
• ? Patients with low‐risk disease had essentially identical risks of significant biochemical recurrence over the study period, regardless of surgical margin status. By contrast, in patients with both intermediate‐ and high‐risk disease, a PSM was a strong predictor of significant biochemical recurrence on univariable analysis. On multivariable analysis, howver, PSM predicted significant disease recurrence in intermediate‐risk disease only.

CONCLUSIONS

• ? PSM is a risk factor for significant biochemical recurrence only in intermediate risk disease.

     

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30–35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin‐positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy.

OBJECTIVE

• ? To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin.

PATIENTS AND METHODS

• ? Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected.
• ? Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin.

RESULTS

• ? At a median follow‐up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%.
• ? On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82–4.32, P < 0.001) compared with the presence of Gleason grade 3.
• ? Linear extent of margin involvement was also associated with recurrence (P= 0.009).
• ? Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence.
• ? On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29–4.03, P= 0.003).

CONCLUSION

• ? The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

     

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.

     

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.

     

Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Men fail active surveillance for a variety of reasons; however, no single reliable biomarker has been found to date which will identify these men from the outset. We know that there are about 35 prostate cancer risk alleles which have been discovered to influence risk of prostate cancer, from large‐scale genome‐wide association studies. Some of these have been associated with aggressive prostate cancer. Nobody has examined the potential for these risk alleles to predict men who might fail active surveillance. This study adds to the growing evidence that single nucleotide polymorphisms may be able to identify men who have aggressive prostate cancers, and that this could be part of a risk algorithm used in active surveillance protocols.

OBJECTIVE

• ? To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance.

PATIENTS AND METHODS

• ? We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate‐specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, ≤50% tumour involvement/core) but instead underwent early radical prostatectomy.
• ? We genotyped these men for 35 CaP risk alleles. We defined ‘unfavourable’ pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen.

RESULTS

• ? In all, 263 men (median age 60 [46–72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have ‘unfavourable’ pathological characteristics.
• ? The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with ‘unfavourable’ pathological characteristics.
• ? Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance.
• ? Carriers of any one of the significantly over‐represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001).
• ? Receiver–operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with ‘favourable’ and ‘unfavourable’ tumour features in their prostatectomy specimen.

CONCLUSION

• ? In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with ‘unfavourable’ pathological characteristics in their radical prostatectomy specimen.

     

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.

     

Population‐based comparative effectiveness of nephron‐sparing surgery vs ablation for small renal masses

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Case series of patients undergoing various forms of ablation show that it is technically feasible and possible for ablation to achieve short‐ and intermediate‐term cancer‐specific survival rates similar to those of controls undergoing partial nephrectomy. This is the first well‐powered study with a controlled design to compare effectiveness between partial nephrectomy and ablation.

OBJECTIVE

• ? To determine, in a population‐based cohort, if disease‐specific survival (DSS) was equivalent in patients undergoing ablation vs nephron‐sparing surgery (NSS) for clinical stage T1a renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? A retrospective cohort study was performed using patients from the Surveillance, Epidemiology and End Results cancer registry with RCC < 4 cm and no evidence of distant metastases, who underwent ablation or NSS.
• ? Kaplan–Meier and Cox regression analyses were performed to determine if treatment type was independently associated with DSS.

RESULTS

• ? Between 1998 and 2007, a total of 8818 incident cases of RCC were treated with either NSS (7704) or ablation (1114).
• ? The median (interquartile range) follow‐up was 2.8 (1.2–4.7) years in the NSS group and 1.6 (0.7–2.9) years in the ablation group, although 10% of each cohort were followed up beyond 5 years.
• ? After multivariable adjustment, ablation was associated with a twofold greater risk of kidney cancer death than NSS (hazard ratio 1.9, 95% confidence interval 1.1–3.3, P= 0.02).
• ? Age, gender, marital status and tumour size were also significantly associated with outcome.
• ? The predicted probability of DSS at 5 years was 98.3% with NSS and 96.6% with ablation.

CONCLUSION

• ? After controlling for age, gender, marital status and tumour size, the typical patient presenting with clinical stage T1a RCC, who undergoes ablation rather than NSS, has a twofold increase in the risk of kidney cancer death; however, at 5 years the absolute difference is small, and may only be realized by patients with long life expectancies.

     

Pathological stage distribution in patients treated with radical prostatectomy reflecting the need for protocol-based active surveillance: results from a contemporary European patient cohort

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Low‐risk prostate cancer is frequently diagnosed in the context of PSA screening or during a routine check‐up. For those patients, to avoid possible overtreatment AS is an increasingly chosen treatment option. However, the concept of AS could possibly misclassify potentially dangerous PCa as a low‐risk disease resulting in inferior cancer control outcomes. In the present study, we could demonstrate that the histopathological results of patients treated by RP in course of AS are significantly better if the selection criteria for AS are entirely fulfilled. Our findings underline the importance of a strict and precise admittance procedure for patients with early prostate cancer who are willing to undergo an AS programme.

OBJECTIVE

• ? To compare the histopathological outcomes of patients treated with radical prostatectomy (RP) after an initial active surveillance (AS) for localized, low‐risk prostate cancers (PCa) among men who fulfilled the Epstein criteria at diagnosis with those who did not.

PATIENTS AND METHODS

• ? In all, 283 patients with localized PCa were initially managed at our institution with AS.
• ? In all, ≈50% originated from the European Randomized Study of Screening for Prostate Cancer (ERSPC) participants from Switzerland: 75 (26.5%) patients underwent treatment during follow‐up and 61 were treated with RP (21.6%).
• ? These patients were stratified into those who did (n= 39) vs those who did not (n= 22) entirely fulfil AS inclusion criteria according to Epstein et al. at PCa diagnosis.

RESULTS

• ? Patients who did completely fulfil the AS inclusion criteria had significantly lower prostate‐specific antigen (PSA)‐values (4.9 vs 7.8 ng/mL; P= 0.02), a significantly lower PSA density at diagnosis (0.09 vs 0.2 ng/mL/ccm; P= 0.007) and at RP, a higher proportion of organ‐confined cancers (89.7% vs 59.1%, P= 0.02) and fewer positive surgical margins (25.6% vs 40.9%).
• ? However, the rate of favourable histopathological outcome, defined as organ‐confined disease with negative surgical margins, was statistically significantly higher in the group fulfilling AS criteria (69.2% vs 40.9%; P= 0.03).

CONCLUSIONS

• ? In our AS series, 26.5% of the patients underwent definitive therapy.
• ? Most patients treated with RP had organ‐confined disease in the majority of cases, especially when the Epstein criteria were rigorously fulfilled at PCa diagnosis.
• ? This underlines the importance of a strict and precise per protocol AS for patients with early PCa, otherwise there is a risk of missing more significant disease.

     

Robotic radical prostatectomy as the initial step in multimodal therapy for men with high-risk localised prostate cancer: initial experience of 160 men

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The choice of therapy with high‐risk localised prostate cancer is difficult and, in the stark absence of any randomised trials, comparative retrospective analyses of case series continue to be necessary. Radical surgery has been considered by many to be inferior to a combination of radiotherapy (RT) and androgen deprivation therapy (ADT), but this changing perhaps coincidentally with the widespread acceptance of robot‐assisted laparoscopic prostatectomy surgery (RALP). Further evidence has now described the long‐term toxicities related to ADT, and this has strengthened a desire amongst many to at least defer, if not avoid, ADT unless absolutely necessary. This article presents a single‐centre experience of RALP in the setting of high‐risk localised disease, and concludes that RALP incorporating the use of post‐operative RT represents a strong perhaps optimum management strategy.

OBJECTIVES

• ? To report the outcome of robotic‐assisted laparoscopic radical prostatectomy (RALP) for men with localised high‐risk prostate cancer at diagnosis.
• ? Although commonly managed by radiotherapy (RT) with prolonged androgen‐deprivation therapy (ADT), we hypothesize that initiation of multimodal therapy with RALP is oncologically efficacious and may allow many men to avoid ADT.

PATIENTS AND METHODS

• ? Between December 2003 and September 2010, 1480 men underwent RALP of whom 160 fulfilled the National Comprehensive Control Network criteria for high‐risk disease (prostate‐specific antigen (PSA) >20 ng/mL and/or clinical stage, cT ≥ 3 and/or biopsy Gleason score ≥8).
• ? Biochemical recurrence (postoperative PSA ≥ 0.2) was used to assess outcome after RALP monotherapy.
• ? Treatment failure was defined as either a rising PSA level after salvage RT or the initiation of ADT.

RESULTS

• ? The mean age ± standard deviation was 63.1 ± 6.3 years. Median PSA level was 9.95 ng/mL (interquartile range 6.0–21.4).
• ? Analysis of prostatectomy specimen showed Gleason 8–10 cancers in 65 (41%), and extracapsular disease, pT ≥ 3, in 96 (60%) of which seminal vesicle invasion was evident in 36 (23%). Downgrading by prostatectomy occurred in 64 (40% of total group) and five (3%) were downstaged to pT2 disease. By contrast, any upgrading occurred in 29 (18% of total group) and upstaging occurred in 68 (43%). The overall positive surgical margin rate was 38%, correlating with stage pT2 (15%) or pT3 (53%).
• ? With median follow‐up of 26.2 months (interquartile range 5.5–37.3), two non‐cancer‐related deaths have occurred (overall survival 98.8%; cancer‐specific survival 100%), and biochemical recurrence has occurred in 53 men (33%). RALP surgery has served as monotherapy (n= 117, 73%), or has been followed by salvage RT (n= 24, 15%) and/or ADT (n= 43, 27%). Overall 2‐year and 3‐year treatment failure was 31 and 41%, respectively.
• ? Serum PSA level was the only independent predictor of overall treatment failure (hazard ratio [HR] 1.02, P= 0.001) although a strong trend was observed for both clinical stage (HR 1.22, P= 0.058) and the number of positive biopsy cores on transrectal biopsy (HR 1.06, P= 0.057).

CONCLUSIONS

• ? RALP incorporating the use of postoperative RT is a good multimodal management strategy for men with this aggressive variant of prostate cancer.
• ? At median follow‐up in excess of 2 years, we found low rates of treatment failure enabling a high proportion of men to remain free of ADT.

     

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.

     

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high‐grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low‐ and intermediate‐risk features; there is a paucity of data about preoperative criteria to identify men with high‐grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high‐grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high‐grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate‐specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high‐grade prostate cancer as to their risk of favourable or unfavourable disease at RP.

OBJECTIVE

• ? To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8–10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).

PATIENTS AND METHODS

• ? The Institutional Review Board‐approved institutional RP database (1982–2010) was analysed for men with high‐Gleason prostate cancer on biopsy; 842 men were identified.
• ? The 10‐year biochemical‐free (BFS), metastasis‐free (MFS) and prostate cancer‐specific survival (CSS) were calculated using the Kaplan–Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8–10 and pT3b or N1.
• ? Preoperative characteristics were compared using appropriate comparative tests.
• ? Logistic regression determined preoperative predictors of unfavourable pathology.

RESULTS

• ? There was favourable pathology in 656 (77.9%) men. The 10‐year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively.
• ? In contrast, men with unfavourable pathological findings had significantly worse 10‐year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001).
• ? In multivariable logistic regression, a prostate‐specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38–3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55–4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59–4.09, P < 0.001), increasing number of cores positive with high‐grade cancer (OR 1.16, 95% CI 1.01–1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17–4.35, P= 0.015) were predictive of unfavourable pathology.

CONCLUSIONS

• ? Men with high‐Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis.
• ? Among men with high‐Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high‐grade cancer and >50% core involvement are predictive of unfavourable pathology.

     

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.

     

Evolution of the clinical presentation of men undergoing radical prostatectomy for high-risk prostate cancer

Study Type – Prognosis cohort series (multi‐centre) Level of Evidence 4 What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at a higher rate in the prostate cancer population. This study adds greater than 20‐year data regarding the continued evolution of high‐risk prostate cancer toward high‐Gleason disease as the sole determinant of high‐risk status prior to radical prostatectomy. It validates the accumulation of multiple‐risk factors as a poor prognostic indicator in a radical prostatectomy population and demonstrates long‐term cancer specific outcomes, extending the findings demonstrated by previous publications.

OBJECTIVE

• ? To investigate the outcomes and potential effect of improved longitudinal screening in men presenting with high‐risk (advanced clinical stage [>T2b], Gleason score 8–10 or prostate‐specific antigen [PSA] level >20 ng/mL) prostate cancer (PC).

PATIENTS AND METHODS

• ? The Institutional Review Board approved, Institutional Radical Prostatectomy Database (1992–2010) was queried for men with high‐risk PC based on D'Amico criteria.
• ? Year of surgery was divided into two cohorts: the Early PSA Era (EPE, 1992–2000) and the Contemporary PSA Era (CPE, 2001–2010).
• ? PC features and outcomes were evaluated using appropriate comparative tests.

RESULTS

• ? In total, 667 men had high‐risk PC in the EPE and 764 in the CPE.
• ? In the EPE, 598 (89.7%) men presented with one high‐risk feature; 173 (29.0%) men had a Gleason score of 8–10 on biopsy. In the CPE, 717 (93.9%) men presented with one high‐risk feature (P= 0.004) and 494 (68.9%) men had a Gleason score of 8–10.
• ? At 10 years, biochemical‐free survival (BFS) was 44.1% and 36.4% in the EPE and CPE, respectively (P= 0.04); metastases‐free survival (MFS) was 77.1% and 85.1% (P= 0.6); and PC‐specific survival (CSS) was 83.3% and 96.2% (P= 0.5).
• ? BFS, MFS and CSS were worse for men with more than one high‐risk feature in both eras.

CONCLUSIONS

• ? Over the PSA era, an increasing percentage of men with high‐risk PC were categorized by a biopsy Gleason score of 8–10.
• ? The accumulation of multiple high‐risk features increases the risk of biochemical recurrence, the development of metastases and death from PC.
• ? BFS, MFS and CSS are stable over the PSA era for these men. The balance between a greater proportion of men having high Gleason disease and a greater proportion with small, less advanced tumours may explain the stability in MFS and CSS over time.

     

Prognostic value of insulin-like growth factor II mRNA binding protein 3 in patients treated with radical prostatectomy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Insulin‐like growth factor II mRNA binding protein 3 (IMP3) is associated with poor outcomes in a variety of malignancies. The role of IMP3 in protate cancer remains poorly understood. IMP3 expression was associated with features of aggressive biology and aggressive prostate cancer recurrence after surgery. Although IMP3 is differentially expressed in patients with features of biologically aggressive prostate cancer, it does not have independent prognostic value in patients treated with RP.

OBJECTIVE

• ? To evaluate the association of insulin‐like growth factor II mRNA binding protein 3 (IMP3) with pathological features and outcomes in patients treated with radical prostatectomy (RP).

PATIENTS AND METHODS

• ? Immunohistochemical staining for IMP3 was performed on archival tissue microarray specimens from 232 consecutive patients treated with RP for clinically localized disease.
• ? None of the patients received neoadjuvant or adjuvant radiation or hormone therapy.
• ? IMP3 expression was histologically categorized as normal or abnormal.
• ? Disease recurrence was classified as aggressive if metastases were present, post‐recurrence prostate‐specific antigen (PSA) doubling time was less than 10 months, or if the patients failed to respond to salvage local radiation therapy.

RESULTS

• ? The median follow‐up was 69.8 months (interquartile range [IQR]: 40.1–99.5).
• ? IMP3 expression was abnormal in 42 (18.1%) of 232 patients.
• ? IMP3 expression was associated with extracapsular extension (P= 0.020), seminal vesicle invasion (P= 0.024), lymphovascular invasion (P= 0.036) and a high pathological Gleason score (P= 0.009).
• ? The 5‐year PSA recurrence‐free survival for IMP3‐negative patients was 83% (standard error [SE]= 3) vs 67% (SE = 8) in IMP3‐positive patients (log‐rank test, P= 0.015).
• ? In a multivariable analysis that adjusted for the effects of surgical margins, extracapsular extension and seminal vesicle invasion, PSA (hazard ratio [HR]: 1.04, P= 0.013), lymph node metastasis (HR: 16.7, P < 0.001) and a high pathological Gleason score (HR 4.3, P= 0.008) were significantly associated with PSA recurrence‐free survival, whereas IMP3 expression was not (P= 0.11). Similarly, IMP3 expression was only associated with aggressive recurrence (HR 3.2, P= 0.006).

CONCLUSION

• ? IMP3 expression is abnormal in approximately one‐fifth of prostate cancers. Although IMP3 is differentially expressed in patients with features of biologically aggressive prostate cancer, it does not have an independent prognostic value in patients treated with RP.

     

Open radical prostatectomy in the elderly: a case for concern?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Adverse outcomes after radical prostatectomy are more often recorded in the elderly. In the USA, elderly patients undergoing radical prostatectomy are treated at institutions where suboptimal outcomes are recorded.

OBJECTIVE

• ? To assess the rate of adverse outcomes after open radical prostatectomy (ORP) in the elderly and to examine the effect of annual hospital caseload (AHC) and academic institutional status on adverse outcomes in these of patients.

PATIENTS AND METHODS

• ? Within the Health Care Utilization Project Nationwide Inpatient Sample, we focused on ORPs performed between 1998 and 2007. Subsequently, we restricted to patients aged ≥75 years.
• ? In both datasets, we examined transfusion rates, intra‐operative and postoperative complication rates, and in‐hospital mortality rates.
• ? Stratification was performed according to AHC tertiles and academic status.
• ? Multivariable logistic regression analyses were fitted.

RESULTS

• ? Of 115 554 ORP patients, 2109 (1.8%) were aged ≥75 years.
• ? In multivariable analyses performed in the entire cohort, elderly age increased homologous blood transfusion rates (P < 0.001), intra‐operative (P= 0.001) and postoperative (P < 0.001) complication rates, and the mortality rate (P= 0.007).
• ? Most elderly were treated at low or intermediate AHC (68.5%) and non‐academic centres (56.2%).
• ? Within the elderly cohort, intra‐operative (2.9%) and postoperative (22.2%) complications tended to be highest at low AHC institutions compared to institutions of intermediate (2.7% and 17.4%) and high AHC (1.7% and 14.5%). Similarly, intra‐operative (2.7% vs 2.1%) and postoperative complications (19.1% vs 13.9%) tended to be higher at non‐academic than academic centres.
• ? In multivariable analyses performed in the elderly subgroup, low AHC predicted higher intra‐operative complications and higher homologous transfusions, whereas non‐academic status predicted higher postoperative complications.

CONCLUSIONS

• ? Adverse outcomes are more often recorded in the elderly.
• ? Most elderly are treated at institutions where suboptimal outcomes are recorded.

     

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.

     

Comparison of outcomes between pure laparoscopic vs robot-assisted laparoscopic radical prostatectomy: a study of comparative effectiveness based upon validated quality of life outcomes

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Few studies exist comparing functional outcomes between RALP and LRP using validated questionnaires. This single surgeon study utilizes data from the EPIC questionnaire that was collected prospectively to compare urinary and sexual function after prostatectomy. In this comparison, return of post‐prostatectomy continence was similar between groups while RALP patients demonstrated earlier return of sexual function.

OBJECTIVE

• ? To compare perioperative, oncological and functional outcomes of laparoscopic radical prostatectomy (LRP) and robot‐assisted laparoscopic radical prostatectomy (RALP) with emphasis on health‐related quality of life (HRQOL) data as few studies exist.

PATIENTS AND METHODS

• ? Patients underwent RALP or LRP by a single, fellowship trained surgeon with a standard clinical care pathway.
• ? HRQOL data using the Expanded Prostate Cancer Index Composite (EPIC) were collected at 0, 3, 6 and 12 months after 175 consecutive LRP and 174 RALP procedures.
• ? Urinary and sexual function outcomes were compared using two methods: (1) EPIC summary/subscale analyses described as percent return to baseline function and (2) traditional single‐question analysis.

RESULTS

• ? The two groups were statistically similar with respect to demographics, clinical stage, perioperative outcomes, stage‐specific surgical margin rates, and baseline urinary and sexual function scores.
• ? There was no statistical difference in postoperative urinary function between RALP and LRP using EPIC or single‐question analyses at 3, 6 and 12 months.
• ? EPIC questionnaire data showed a greater return to baseline sexual function over time (mixed model analysis) in RALP than in LRP patients who had a bilateral nerve sparing procedure (Sexual Summary Score, P= 0.005; Sexual Function and Bother Subscales, P= 0.007).
• ? Using EPIC, RALP patients receiving a bilateral nerve sparing procedure showed improved percent return to baseline potency at 3 and 6 months (P < 0.025) compared with LRP patients, but had similar outcomes at 12 months (73.7% vs 66.2%, P= 0.3).
• ? Single‐question analysis suggested improved potency after RALP compared with LRP, with a greater percentage of RALP patients reporting successful sexual intercourse in the past 4 weeks (87.5% vs 66.7% at 12 months, P= 0.06).

CONCLUSIONS

• ? When comparing surgical techniques, RALP and LRP groups showed statistically similar postoperative urinary function outcomes.
• ? RALP patients had an earlier return of sexual function when compared with LRP patients after a bilateral nerve sparing procedure.

     

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.