Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guérin.

BACKGROUND AND OBJECTIVES: To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guérin (BCG) therapy. MATERIALS AND METHODS: This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. RESULTS: Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values <0.001, 0.03, 0.02, and 0.006, respectively) and when associated with positive MMP9 or p21, it was significantly correlated to progression (log rank P values 0.01 and 0.04, respectively). CONCLUSION: Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings.

Final outcomes of patients with low-risk prostate cancer suitable for active surveillance but treated surgically.

OBJECTIVE: To study the outcomes of a contemporary cohort of patients referred from around the UK with low-risk prostate cancer consistent with the UK National Institute for Health and Clinical Excellence guidelines for active surveillance but who were treated with laparoscopic radical prostatectomy (LRP) in a single surgeon series. PATIENTS AND METHODS: From 1080 consecutive patients who underwent LRP between March 2000 and April 2008, 549 patients (51%) had low preoperative risk disease (PSA level <10 ng/mL, clinical stage < or =T2a and biopsy Gleason score < or =6). The pathological outcomes of these 549 patients as well as a subgroup of 74 patients with preoperative prediction of 'insignificant' disease were assessed. RESULTS: The mean age of the patients was 61 years, the mean (range) PSA level was 6.1 (1-9) ng/mL; 38% of patients were staged as cT2a. In all, 126 patients (23%) were upgraded on final pathology to Gleason score > or =7. In all, 29 patients (5%) had extraprostatic extension with seminal vesicle invasion in five (0.9%). Of the 74 patients with preoperative prediction of insignificant disease, 61% had significant disease with 16% upgraded to an intermediate-risk group. Overall, there were positive margins in 44 patients (8.0%) and biochemical failure occurred in six patients (1.1%) with a median follow-up of 28 months. CONCLUSION: In this contemporary UK cohort of patients with apparently low- or favourable-risk prostate cancer, 23% will have higher grade disease than preoperatively predicted. Even though active surveillance is increasingly being recommended for managing low-risk localized prostate cancer, patients and their physicians need to be aware of the potential for harbouring more significant disease.

Strategies to preserve prostate health.

The present review addresses strategies to preserve prostate health, tackling the three most common prostatic problems with which men present to physicians, namely, prostate hypertrophy, prostatitis and prostate cancer. Unfortunately since a clear etiology does not exist for each of these problems, we have to rely on experimental research, epidemiologic and clinical data to design prevention strategies. A number of modifiable targets have been identified and some are cross-shared between these three very prevalent entities. However, since the pathogenesis of each condition seems multifactorial, and the interconnections between them inadequately understood, chemopreventive strategies are still in their infancy even after very large clinical trials -which produced often more questions than they delivered answers- have already been performed.

The impact of training on service provision in laparoscopic radical prostatectomy.

OBJECTIVE: To address concerns about the impact of training on patient outcomes during the 'learning curve' for laparoscopic radical prostatectomy (LRP), we compare the results of our patients undergoing LRP with and without trainees performing a substantial proportion of the cases. PATIENTS AND METHODS: In all, 771 consecutive cases of LRP were performed or supervised by one surgeon during a 7.5-year period, of which 114 (15%) were training cases. A five-port transperitoneal technique was used in the first 111 patients and an extraperitoneal approach in the remaining 660. Patient, operative and oncological outcome variables were compared using an independent samples t-test if continuous or with Fisher's exact test for rates. RESULTS: There were no differences in preoperative patient or cancer characteristics with the exception of body mass index (BMI) which was lower in the training cases (medians 25 and 26 kg/m(2), P = 0.02) and patient age which was higher (medians 64 and 62 years, P < 0.001). Operative time, which was longer in training cases (medians 200 and 175 min, P < 0.001) was the only significantly different operative variable between the groups. There were no statistically significant differences in postoperative (duration of catheterization, hospitalization time, complication rates, biochemical recurrence and pad-free rates at 1 year) or pathological (gland weight, positive surgical margin rate) outcomes between the groups. As Fellows did not perform the posterior or apical dissection steps in nerve-sparing cases, no evaluation of potency outcomes is included. CONCLUSIONS: Training cases took a median of 25 min longer to complete than non-training cases. However, other perioperative measures, complications rates and cancer outcomes were similar. Adequately supervised training in LRP does indeed take additional time but is essential for the dissemination of surgical skills and preservation of acceptable outcomes.

The first 1000 cases of laparoscopic radical prostatectomy in the UK: evidence of multiple 'learning curves'.

OBJECTIVE: To report the initial experience of one surgeon, with contemporary experience of both open radical prostatectomy (ORP) and reconstructive laparoscopy, in laparoscopic radical prostatectomy (LRP) in 1000 patients, and to investigate the rate of change of various outcome variables for this procedure with time. PATIENTS AND METHODS: Between March 2000 and December 2007, 1000 consecutive patients with clinical stage T < or = 3aN0M0 prostate cancer underwent LRP, either supervised (17%) or performed (83%), by one surgeon. The median prostate-specific antigen (PSA) level was 7.0 (1-50) ng/mL and median Gleason sum 6 (4-10); the clinical stage was T1 in 46.9%, T2 in 49.8% and T3 in 3.3%. RESULTS: The median (range) operative duration was 177 (78-600) min. There was one conversion (patient 8) to open surgery. The median blood loss was 200 (10-1300) mL and four patients were transfused (0.4%). The median postoperative hospital stay was 3.0 (3-28) nights. The median catheterization time was 10.0 (0.8-120) days. There were 48 complications (4.8%) requiring surgical intervention in 33 (3.3%) patients, 58% of these as a day-case admission. The positive margin rates according to d'Amico risk groups were: low, 9.1%; intermediate, 20.3%; and high, 36.8%. The overall positive margin rate was 13.3%. The PSA level was < or =0.1 mg/L at 3 months in 99.1% of patients. At a mean follow-up of 27.7 (3-72) months, 96.1% of patients were free of biochemical recurrence. In patients with a follow-up of > or =24 months potency rates peaked in the series at 86% for all men and 94% for men aged < or =65 years, and continence rates at 98% before declining thereafter in men with a shorter follow-up. CONCLUSION: The learning curve for operating time and blood loss was overcome within the first 100-150 cases, but complication and continence rates took 150-200 cases to reach a plateau. The longest learning curve was for potency, which did not stabilize until 700 cases. These learning curves are likely to be considerably shorter when surgeons are taught in departments with a high throughput of cases but both surgeons and patients should be aware of them. In view of these findings, the authors recommend that LRP should not be self-taught and should be learned within an immersion teaching programme. Even then, a large surgical volume is likely to be needed to maintain clinical outcomes at the highest level.

Does intrafascial dissection during nerve-sparing laparoscopic radical prostatectomy compromise cancer control?

UNLABELLED: To assess whether oncological outcomes are compromised by adopting the curtain dissection (CD) technique (high incision of the peri-prostatic fascia) during nerve-preserving radical prostatectomy (RP). PATIENTS AND METHODS: In all, 973 laparoscopic RPs (LRPs) were performed or supervised by one surgeon between March 2000 and October 2007 for cT1-3 N0M0 prostate cancer, of which 510 included bilateral neurovascular bundle preservation. A CD technique was used in 240 men and a standard dissection (StD) technique was used in 270, considered the control group. The technique was extraperitoneal, used five ports and included preservation of the seminal vesicle tips. Thermal energy was not used posterior or lateral to the prostate in either group. Patient, operative and oncological outcome variables were compared using an independent-sample t-test if continuous or with Fisher's exact test for rates. RESULTS: Patient and cancer characteristics before LRP were similar for the CD and StD groups, and there were no significant perioperative differences either. Positive margins occurred in 11.7% of the CD group and 11.1% of the StD group (P = 0.95). At a mean (range) follow-up of 11.7 (3-24) months for the CD group and 13.1 (3-24) months for the StD group, biochemical recurrence rates were 0% and 1.1%, respectively (P = 0.30). Potency (CD, 62%; StD, 61%; P = 0.89) and continence rates (StD, 97%; CD, 98%; P = 0.83) were comparable between the groups, but there was a statistically significant earlier return to continence in the CD group (P < 0.001 at 3 months). CONCLUSIONS: For carefully selected men there appears to be no compromise in cancer control with intrafascial dissection in the short term. However, equally there appears to be no significant improvement in potency after LRP. The earlier return to continence after intrafascial nerve-sparing suggests reduced dissection of periurethral supports rather than preservation of additional autonomic nerve fibres.

Tamsulosin oral controlled absorption system (OCAS) in the treatment of benign prostatic hypertrophy.

The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the alpha(1a) and alpha(1d) adrenergic receptor subtypes. The oral-controlled absorption system (OCAS((R))) represents a drug delivery refinement that incorporates a matrix of gel-forming and gel-enhancing agents to promote a constant drug release independent of environmental food or fluid. There are clinical data to support the concept that drug peaks are lessened and that drug release continues throughout the alimentary tract due to the OCAS formulation. Furthermore this equates with less adverse effects on physiologic parameters. To date however improvements in cardiovascular symptoms such as dizziness, headache and syncope have not been demonstrated in healthy men. Ejaculatory dysfunction appears less problematic with the OCAS preparation. Tamsulosin OCAS may be of greatest benefit to men with cardiovascular co-morbidities taking anti-hypertensive medications that might predispose them to symptomatic hypotensive episodes. It will be necessary to evaluate this group of men more closely in further trials to determine what they stand to gain from changing medications, and then relate this to drug costs to draw a final conclusion as to the place of tamsulosin OCAS in contemporary urological practice.

Curtain dissection of the lateral prostatic fascia and potency after laparoscopic radical prostatectomy: a veil of mystery.

OBJECTIVE: To assess the effect on potency recovery of incorporating a high incision of the lateral prostatic fascia (LPF) or curtain dissection (CD) into our technique of laparoscopic nerve-sparing radical prostatectomy (LNSRP). PATIENTS AND METHODS: In all, 137 bilateral neurovascular bundle (NVB) preserving LNSRPs were performed, incorporating curtain dissection (CD) of the LPF. Potency was assessed at 1, 3, 6 and 12 months using validated questionnaires and compared with a control group (CG) of standard NVB preservation. RESULTS: There were no conversions to open surgery in either group. The median operative duration in the CD group and the CG was 178 min and 174 min (P = 0.04), blood loss was 300 mL and 200 mL (P = 0.01), and the positive margin rate was 16.1% and 24.1% (P = 0.04), respectively. At a mean follow-up of 5.8 months in the CD group and 28.2 months in the CG, potency rates were 21.1% and 8.8% at 1 month (P = 0.01), and 68.4% and 67.2% at 12 months (P = 1.00), respectively. CONCLUSION: The potency rate was significantly higher in the CD group at 1 month than in the CG, thereafter the rates were similar between the groups. We think that the merit of this technique is in improved visualization of the basal prostatic contour during antegrade NVB dissection, rather than preserving important nerve fibres. This may explain the lower basal positive margin rate in the CD group of 0% vs 5.8% in the CG (P = 0.007).

The once and future role of cytoreductive nephrectomy.

The role of nephrectomy in the setting of metastatic renal cell carcinoma has long been controversial and has continued to evolve over the last two decades. The practice of cytoreductive nephrectomy has only recently been widely accepted following the publication of 2 large multi-center randomized controlled trials that established a survival benefit for those patients undergoing nephrectomy followed by interferon treatment. Half a decade later, the new paradigm looks set to be questioned with the rapid emergence of tyrosine kinase inhibitors (TKIs). This article reviews the evolution of cytoreductive nephrectomy and speculates on its role in the new frontier of molecular targeting for metastatic renal cell carcinoma.

Systematic lateral prostate biopsy--are the benefits worth the costs?

PURPOSE: We quantified the additional benefit of routinely adding 4 lateral biopsies to the initial sextant and transrectal ultrasound lesion targeted biopsy pattern in terms of cancer detection. We related this to costs. MATERIALS AND METHODS: Prospective data were accrued on 1,010 consecutive patients referred for initial transrectal ultrasound directed prostate biopsy between June 16, 2000 and September 1, 2005. Costs were estimated for the pathology and clinical departments in terms of staff time. RESULTS: Of 1,010 patients 494 (48.9%) were diagnosed with prostate adenocarcinoma. In these cases 411 cancers (83%) were found in medial samples, including 107 (22%) isolated to medial cores alone and 304 (62%) in medial and lateral cores. Only 55 patients (5.4%) had cancer isolated to systematic lateral cores. Of these cancers 30 (3%) were defined as clinically significant based on Gleason grade 7 or greater, or Gleason grade 6 involving more than 5% of any core. There was a 24% increase in biopsy related costs and a 36% increase in pathology costs associated with the 4 additional lateral biopsies. CONCLUSIONS: Medial sextant and targeted biopsy directed at transrectal ultrasound identified lesions detects 94.6% of the prostate cancer that is detected with a 10 core biopsy protocol. The latter detects an extra 3% of clinically significant prostate cancer, while increasing costs by 30%. It is important to consider the absolute benefits of systematic lateral prostate biopsy in light of this additional expense when selecting an appropriate transrectal ultrasound biopsy regimen for a patient suspected of harboring prostate cancer.

The nature and extent of urinary morbidity in relation to prostate brachytherapy urethral dosimetry.

PURPOSE: This study investigates whether the location and dose of urethral radiation received during transperineal interstitial permanent prostate brachytherapy determine the degree and type of urinary symptoms experienced subsequently. METHODS AND MATERIALS: Data from a prospectively acquired database of 219 men treated with transperineal interstitial permanent prostate brachytherapy using (125)I (prescribed dose 145Gy) between May 2001 and June 2003 were reviewed. To assess the effect of regional urethral dosimetry, the prostate was divided into equal thirds (proximal, mid, and apical) with doses beyond this considered distal. Mean and peak doses for each region were correlated with total International Prostate Symptom Score (IPSS) and the irritative and obstructive components of the score. IPSS values at 1 month postimplant, time to resolution of IPSS, and the need for catheterization were used as outcome variables and analyzed with respect to dose using logistic and linear regression. RESULTS: Peak and average doses with standard deviations to the proximal urethra were 168 (24) and 147 (24)Gy, mid prostatic urethra 192 (24) and 181 (21)Gy, and apical urethra 201 (28) and 192 (26)Gy. Catheterization was required for 28 men and was predicted by larger pretreatment transrectal ultrasound (TRUS) volume (OR 1.06 per unit change; 95% CI 1.03-1.10; p<0.001) and lower UV(150) (OR 0.30; 95% CI 0.13-0.68; p=0.004) in multivariate analysis. Greater IPSS at baseline (p<0.001) and preoperative TRUS volume (p=0.012) but conversely smaller D(30) doses (p=0.003) were predictive of IPSS outcomes at 1 month. IPSS returned to within two points of baseline for 72.2% of men by 1 year and 83.3% by 24 months. This was predicted by higher IPSS at baseline (OR 6.0; 95% CI 2.72-13.22; p<0.001), higher D(30) (OR 1.17; 95% CI 1.01-1.36; p=0.031), and lower V(100) (OR 0.39; 95% CI 0.22-0.70; p=0.002). Prostatic urethral segmental dosimetry failed to predict the need for catheterization, the nature of the urinary symptoms, or their time to resolution. CONCLUSIONS: Previously identified factors of importance for urinary morbidity such as pretreatment prostate volume and baseline urinary function were reemphasized in this study. Regional urethral dosimetry within contemporary practice does not seem to influence the nature or extent of urinary symptoms after prostate brachytherapy. Consequently, region sparing dosimetric modifications are not warranted to alter symptomatic outcomes.

Consolidative renal cell carcinoma metastatectomy for partial response after multitargeted tyrosine kinase inhibitor therapy.

The advent of molecularly targeted agents is rapidly changing the management of metastatic renal cell carcinoma. A case in which surgical metastatectomy was used in the setting of dramatic but incomplete disease response to sunitinib is presented. Some of the issues complicating operative intervention in the setting of multitargeted tyrosine kinase inhibitors are discussed.

Management of low-stage testicular seminoma.

Testicular seminoma represents a modern model of a multidisciplinary approach to a curable neoplasm. Surgeons, radiation oncologists, and medical oncologists play an important role in disease detection, diagnosis, treatment, and follow-up. This article focuses on the management of men who have early-stage seminoma, which represents stage I and IIa (minimal retroperitoneal spread). In stage I disease, the major controversies continue to revolve around surveillance versus adjuvant treatment and more recently adjuvant radiotherapy or carboplatin-based chemotherapy. Focus on long-term complications, such as cardiovascular disease, gastrointestinal disease, and secondary cancers, has led to the concept of increased surveillance with therapy for those who relapse. Radiation therapy remains the mainstay of therapy for patients who have stage IIa disease.

The continuing importance of transrectal ultrasound identification of prostatic lesions.

PURPOSE: In light of a recent tendency toward systematic nontargeted biopsy we reassessed whether identification and biopsy of ultrasonographically suspicious lesions contribute to the detection of prostate cancer. MATERIALS AND METHODS: We reviewed prospectively gathered data on 7,426 transrectal ultrasound directed prostatic biopsies performed at our institution between June 16, 2000 and September 1, 2005. Patients underwent systematic biopsy (6 to 10 cores on initial biopsy and 13 to 15 on rebiopsy) with additional sampling of visible suspicious lesions. The RR for finding cancer in transrectal ultrasound positive and negative patients was calculated for likely independent prognostic variables. RESULTS: A total of 3,828 biopsies (51.5%) were transrectal ultrasound negative and 3,598 (48.5%) were transrectal ultrasound positive. Prostate cancer was detected in 3,258 biopsies (43.9%). For each independent variable the RR for prostate cancer was higher if a sonographic lesion was present. A lesion increased the likelihood of cancer detection (57.8% vs 30.8%, RR 1.8). Biopsies from lesions identified by transrectal ultrasound had a greater median percent of the core involved with cancer (50% vs 10%, p <0.001) and they were more likely to have Gleason score 7 or greater (69.3% vs 28.3%, p <0.001). CONCLUSIONS: Biopsies taken when a prostatic lesion is identified by transrectal ultrasound are almost twice as likely to show cancer than when no lesion is visible. These cancers are of higher grade and volume and, therefore, they are more clinically significant. The search for and targeted biopsy of suspicious lesions seen on transrectal ultrasound remains important for prostate cancer diagnosis.

Preoperative evaluation of the "hostile pelvis" in radical prostatectomy with computed tomographic pelvimetry.

OBJECTIVE: To determine whether preoperative pelvimetry based on computed tomography (CT) can be used to predict technical difficulties during open radical prostatectomy (RP). PATIENTS AND METHODS: An open RP database accrued prospectively between January 1997 and June 2005 was used to identify 450 patients with preoperative pelvic imaging. Of these, 165 had adequate imaging of the pelvis with CT to allow pelvimetry using software provided with the medical imaging records. Several pelvic measurements were recorded in conjunction with body mass index and transrectal ultrasonographic estimates of prostatic volume. Outcome measures used to reflect technical surgical difficulties included operative duration, blood transfusion requirements within 30 days of RP, the pathological positive surgical margin and prostatic capsular breech rate. Logistic and linear regression analyses were used to determine the relationship between variables before and after RP. RESULTS: The selected pelvimetric measurements failed to predict either operative duration or the peri-operative blood transfusion requirement. Prostatic volume was predictive of operative duration; for every increase of 20 mL in prostate volume the duration increased by 8.4 min. Although pelvimetric measures failed to predict positive surgical margins at pathology, the transverse diameter predicted the likelihood of a positive margin due to capsular breech. With every 8.6 mm (1 sd) decrease in transverse diameter, the odds of a capsular breech resulting in positive surgical margins increased 5.3 times (95% confidence interval 2.1-20.0, P = 0.002). CONCLUSIONS: Although the "hostile pelvis" influences the likelihood of prostatic capsular breech resulting in positive surgical margins, CT pelvimetric screening of patients before RP is unlikely to be cost-effective. Routine pelvic CT in the evaluation of patients before RP is not supported.

Randomized trial comparing holmium laser enucleation of prostate with plasmakinetic enucleation of prostate for treatment of benign prostatic hyperplasia.

OBJECTIVES: To compare the alternative energy sources of the holmium:yttrium-aluminum-garnet laser and bipolar plasmakinetic energy for endoscopic enucleation. METHODS: A prospective, randomized controlled trial was undertaken, with 20 patients assigned to each group. The preoperative and postoperative measures included transrectal ultrasound-assessed prostate volume, postvoid residual urine volume, and urodynamic evaluation findings. The intraoperative measures included procedure length, energy use, and specimen weight. All adverse events were recorded at each postoperative visit in a 1, 3, 6, and 12-month protocol. RESULTS: No differences were found in the preoperative characteristics between the two groups. The significant differences favoring holmium laser enucleation of the prostate compared with plasmakinetic enucleation of the prostate were seen in the operative time (43.6 versus 60.5 minutes), recovery room time (47.1 versus 65.6 minutes), and bladder irrigation requirement (5% versus 35%). The outcomes after holmium laser enucleation of the prostate and plasmakinetic enucleation of the prostate were in all other respects similar by the postoperative outcome measures assessed. CONCLUSIONS: Plasmakinetic enucleation of the prostate is a safe and technically feasible procedure for the enucleation of prostatic adenomata. Plasmakinetic enucleation of the prostate is limited by the longer operative and recovery room times, as well as a more pronounced postoperative irrigation requirement because of reduced visibility and a greater propensity for bleeding. The transfusion rates and catheterization and hospitalization times were similar. The optimal energy source for enucleation should still be considered the holmium laser, but bipolar energy can be considered by users already experienced with holmium laser enucleation of the prostate.