Irbesartan promotes erection recovery after nerve‐sparing radical retropubic prostatectomy: a retrospective long‐term analysis

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction following radical prostatectomy (RP) is among the most common and dreaded adverse effects of the surgery. Multiple studies confirm the potential benefit of various drug classes to accelerate the return of erectile function (EF) after RP. There is pre‐clinical evidence supporting the use of angiotensin‐receptor blockers (ARBs) for this purpose, although this has not been studied in humans. The present study shows that there may be a benefit in the recovery of EF post‐RRP in patients taking a daily dose of irbesartan, an ARB, following RRP. In addition, the use of irbesartan may curb the loss of stretched penile length which occurs postoperatively. Further study in the form of prospective, randomized, placebo‐controlled clinical trials are necessary to confirm these findings.

OBJECTIVE

• ? To evaluate retrospectively the potential benefit of administering irbesartan, an angiotensin‐receptor blocker, to improve erectile function (EF) recovery after nerve‐sparing radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

• ? Before surgery potent patients who underwent nerve‐sparing RRP between April and December 2009 elected to start daily oral irbesartan 300 mg on postoperative day 1 (n= 17). A contemporaneously clinically matched cohort consisting of patients who declined irbesartan use served as the control group (n= 12).
• ? Postoperative ‘on demand’ use of erectile aids (phosphodiesterase type 5 [PDE5] inhibitors and intracavernous injections) was adopted.
• ? Potency was monitored by the administration of International Index of Erectile Function‐5 (IIEF‐5) questionnaires before surgery and at early (3 months) and long‐term (12 and 24 months) postoperative intervals.
• ? Stretched penile length (SPL) was measured both immediately and 3 months after surgery.

RESULTS

• ? EF status was no different between groups at baseline (P > 0.05).
• ? While the IIEF‐5 scores at 24 months after surgery were statistically similar between the two groups (control = 15.2 ± 2.0, irbesartan = 14.1 ± 3.1, P= 0.77), at 12 months the IIEF‐5 scores of the irbesartan group were significantly higher than those of the control group (14 ± 2.6 vs. 7.2 ± 1.6, P < 0.05).
• ? The proportional loss of SPL after RRP was less in the irbesartan than in the control group at 3 months (–0.9 ± 1.5% vs –5.6 ± 1.5, P < 0.05).

CONCLUSION

• ? Regular irbesartan use after nerve‐sparing RRP in patients with normal preoperative erectile function could improve EF recovery after surgery and mitigate early loss of SPL.

     

The impact of nerve‐sparing robot‐assisted radical prostatectomy on lower urinary tract function: Prospective assessment of patient‐reported outcomes and frequency volume charts

Aims

To elucidate the effects of a nerve‐sparing (NS) procedure on lower urinary tract symptoms (LUTS) and urinary function after robot‐assisted radical prostatectomy (RARP), the associations between the NS procedure and LUTS and urinary function were investigated.

Methods

The participants in this study were 200 consecutive patients who underwent RARP. These patients were categorized into unilateral and bilateral NS groups and the non‐NS group. The International Prostate Symptom Score (IPSS), quality of life (QOL) index, frequency‐volume chart, uroflowmetry, 1‐h pad test, and the 5‐item International Index of Erectile Function (IIEF‐5) questionnaire were evaluated before and after RARP.

Results

The total IPSS score was significantly lower in the unilateral (P = 0.03) and bilateral NS groups (P = 0.03) than in the non‐NS group after RARP. Diurnal maximum voided volume (MVV) values were significantly greater in the bilateral NS group than in the non‐NS group after RARP (P = 0.002). Nocturnal frequency was significantly decreased in the unilateral NS group than in the non‐NS group after RARP (3 months P = 0.01, 12 months P = 0.01). Erectile function was significantly better in both the unilateral NS group (P < 0.0001) and the bilateral NS group (P = 0.02) than in the non‐NS group 12 months after RARP.

Conclusions

The NS procedure in RARP has the possibility to improve not only erectile function, but also LUTS, owing to both the increase of MVV and the decrease of nocturia. Therefore, the NS procedure is also recommended from the viewpoint of early improvement of LUTS and lower urinary tract dysfunction after RARP.     

The timing of penile rehabilitation after bilateral nerve‐sparing radical prostatectomy affects the recovery of erectile function

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

OBJECTIVE

To define if erectile function (EF) outcomes were better in men with early institution of penile rehabilitation after radical prostatectomy (RP), as one of the mechanisms by which patients fail to recover EF after RP is collagenization of corporal smooth muscle with subsequent venous leak development, and rehabilitation is aimed at preventing these structural alterations.

PATIENTS AND METHODS

The study population comprised patients who: (i) had clinically organ‐confined prostate cancer; (ii) had fully functional erections, corroborated by the partner; (iii) had bilateral nerve‐sparing RP; and (iv) committed to pharmacological penile rehabilitation. Patients completed the International Index of Erectile Function (IIEF) serially after RP. Patients were instructed to obtain three erections/week using initially sildenafil, and if unsuccessful, then intracavernous injections. Patients were subdivided into those starting rehabilitation at <6 months after RP (early) and those starting at ≥6 months after RP (delayed).

RESULTS

There were 48 patients in the early group and 36 in the delayed group; patients in both groups were matched for age, comorbidity status and baseline EF. The mean duration after RP at the time of starting penile rehabilitation was 2 and 7 months in the early and delayed groups, respectively (P < 0.01). At 2 years after surgery there was a highly statistically significant difference in IIEF EF domain score between the early and delayed groups (22 vs 16, P < 0.001). There were also statistically significant differences between the groups in the percentage of men at 2 years after RP who had unassisted functional erections and sildenafil‐assisted functional erections (58% vs 30%, P < 0.01; 86% vs 45%, P < 0.01, respectively).

CONCLUSIONS

These data suggest that delaying the start of penile rehabilitation after RP is associated with poorer outcomes for EF.     

Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil

OBJECTIVE

To evaluate the effect of low‐dose sildenafil for rehabilitating erectile function after nerve‐sparing radical prostatectomy (NSRP), as the delay to recovery of erectile function after NSRP remains under debate.

PATIENTS AND METHODS

Forty‐three sexually active patients had a NSRP; at 7–14 days after surgery they had a Rigiscan® (Dacomed Corporation, Minneapolis, MN, USA) measurement of nocturnal penile tumescence and rigidity (NPTR). To support the recovery of spontaneous erectile function, 23 patients with preserved nocturnal erections received sildenafil 25 mg/day at night. A control group of 18 patients were then followed but had no phosphodiesterase‐5 inhibitors. The International Index of Erectile Function (IIEF)‐5 questionnaire was completed 6, 12, 24, 36 and 52 weeks after NSRP.

RESULTS

Of the 43 patients, 41 (95%) had one to five erections during the first night after catheter removal. In the group using daily sildenafil the mean IIEF‐5 score decreased from 20.8 before NSRP to 3.6, 3.8, 5.9, 9.6 and 14.1 at 6, 12, 24, 36 and 52 weeks after NSRP, respectively. In the control group the respective scores were 21.2, decreasing to 2.4, 3.8, 5.3, 6.4 and 9.3. There was a significant difference in IIEF‐5 score and time to recovery of erectile function between the groups (P < 0.001), with potency rates of 86% vs 66%.

CONCLUSION

The measurement of NPTR after NSRP showed erectile function even the ‘first’ night after catheter removal. In cases of early penile erection, daily low‐dose sildenafil leads to a significant improvement in the recovery of erectile function.     

The impact of cavernosal nerve preservation on continence after robotic radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Continence after radical prostatectomy (RP) has been linked to surgical techniques including careful dissection of the neurovascular bundles, bladder neck preservation, sparing of the puboprostatic ligaments and reconstruction of the posterior urethral plate or total reconstruction of the vesico‐urethral junction. Several authors have reported that men undergoing bilateral nerve‐sparing have quicker and better recovery of continence than men undergoing partial or non‐nerve‐sparing procedures. Others have reported that preoperative variables have a greater effect than technique on postoperative return to continence. We examine the association between baseline characteristics (age, International Index of Erectile Function [IIEF‐5] score, American Urological Association symptom score, body mass index [BMI], clinical T stage, Gleason score, and prostate‐specific antigen level), nerve‐sparing status, learning curve and overall continence at 1, 3 and 12 months after robotic RP. In addition, nerve‐sparing status was physically verified by comparing the amount of extraprostatic tissue seen on the wide excision side and nerve‐sparing side for unilateral nerve‐sparing procedures. After multivariate analysis, age, IIEF‐5 and BMI were found to affect continence in a statistically significant fashion, while nerve‐sparing status did not significantly affect continence.

OBJECTIVE

? To evaluate associations between baseline characteristics, nerve‐sparing (NS) status and return of continence, as a relationship may exist between return to continence and preservation of the neurovascular bundles for potency during radical prostatectomy (RP).

PATIENTS AND METHODS

? The study included 592 consecutive robotic RPs completed between 2002 and 2007. ? All data were entered prospectively into an electronic database. ? Continence data (defined as zero pads) was collected using self‐administered validated questionnaires. ? Baseline characteristics (age, International Index of Erectile Function [IIEF‐5] score, American Urological Association symptom score, body mass index [BMI], clinical T‐stage, Gleason score, and prostate‐specific antigen level), NS status and learning curve were retrospectively evaluated for association with overall continence at 1, 3 and 12 months after RP using univariate and multivariable methods. ? Any patient taking preoperative phosphodiesterase inhibitors was excluded from the postoperative analysis.

RESULTS

? Complete data were available for 537 of 592 patients (91%). ? Continence rates at 12 months after RP were 89.2%, 88.9% and 84.8% for bilateral NS, unilateral NS and non‐NS respectively (P= 0.56). ? In multivariable analysis age, IIEF‐5 score and BMI were significant independent predictors of continence. ? CavernosalNS status did not significantly affect continence after adjusting for other co‐variables.

CONCLUSION

? After careful multivariable analysis of baseline characteristics age, IIEF‐5 score and BMI affected continence in a statistically significant fashion. This suggests that baseline factors and not the physical preservation of the cavernosal nerves predict overall return to continence.     

A double‐blind placebo‐controlled study of the efficacy and safety of pentoxifylline in early chronic Peyronie’s disease

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

OBJECTIVE

To analyse the safety and efficacy of pentoxifylline sustained‐release (PTX‐SR) treatment in patients with early chronic Peyronie’s disease (PD).

PATIENTS AND METHODS

In all, 228 patients with a mean (sd ) age of 51 (9) years who had early chronic PD were randomized to receive 400 mg PTX‐SR (Apo‐Pentoxifylline, Apotex Inc., Toronto, Canada) twice daily (group 1, 114) or similar regimen of placebo (group 2, 114) for 6 months. A medical history was taken and the men had a complete physical examination. The following variables were assessed before and after therapy: penile curvature and penile artery spectral traces (end‐diastolic velocity, EDV, peak systolic velocity, PSV, and resistivity index, RI, of the right and left cavernous arteries assessed with dynamic penile duplex ultrasonography), plaque characteristics (assessed by penile X‐ray and penile ultrasonography), pain (assessed by visual analogue scale), erectile function (assessed by the International Index of Erectile Function, IIEF questionnaire), treatment satisfaction (assessed by Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire), and side‐effects. Patient perception of penile curvature and plaque size, and mean weekly intercourse attempts were also assessed.

RESULTS

Overall, 36.9% of patients who received PTX‐SR reported a positive response, vs only 4.5% in the placebo group. Of patients in PTX‐SR group, 12 (11%) had disease progression, vs 46 (42%) in placebo group (P = 0.01). Improvement in penile curvature (P = 0.01), and plaque volume (P = 0.001) was significantly greater in patients treated with PTX‐SR than placebo. The increase in IIEF total score was significantly higher in the PTX‐SR group (P = 0.02). Mean PSV changes after therapy compared to baseline were statistically significant between PTX‐SR (right, +11.4%, left, +11.7%) and placebo‐treated (+0.2% and ?4.2%, respectively) patients (both P = 0.04).

CONCLUSIONS

PTX‐R was moderately effective in reducing penile curvature and plaque volume in patients with early chronic PD. Further studies with different treatment regimens are needed to better elucidate the beneficial effects of PTX‐SR in PD.     

Early oncological outcomes of robot‐assisted radical prostatectomy for high‐grade prostate cancer

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

OBJECTIVE

To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence‐free survival (BCRFS) after robot‐assisted radical prostatectomy (RARP).

PATIENTS AND METHODS

Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of ≥0.2 ng/mL with a second rising value. The Kaplan–Meier method and log‐rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling.

RESULTS

The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow‐up was 23 (10–46) months and 19 (7–37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se ) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS.

CONCLUSIONS

Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high‐grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours.     

The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double‐blind placebo‐controlled and randomized study

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

OBJECTIVE

To determine the safety and efficacy of adjunctive bupropion sustained‐release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side‐effect of SSRIs and the most effective treatments have yet to be determined.

PATIENTS AND METHODS

The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression‐Sexual Function (CGI‐SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period.

RESULTS

After 12 weeks of treatment, the mean (sd ) scores for CGI‐SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI‐SF score were correlated (P= 0.003). In linear regression analyses the CGI‐SF score was not affected significantly by the duration of SD, type of SSRI used and age.

CONCLUSIONS

Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.     

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy

Study Type – Prognosis (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Cardiovascular disease is a leading cause of death in prostate cancer patients. Pretreatment ED is a surrogate for vascular pathology. Aggressive treatment of medical co‐morbidity in prostate cancer patients may positively impact overall survival.

OBJECTIVE

• ? To evaluate the relationship between pre‐treatment erectile function and all‐cause mortality in patients with prostate cancer treated with brachytherapy.

PATIENTS AND METHODS

• ? In all, 1279 consecutive patients with clinically localized prostate cancer and pre‐implant erectile function assessed by the International Index of Erectile Function‐6 (IIEF‐6) underwent brachytherapy.
• ? Potency was defined as an IIEF‐6 score of ≥13 without pharmacological or mechanical support.
• ? Patients were stratified into IIEF‐6‐score cohorts (≤12, 13–23 and 24–30).
• ? The median follow‐up was 5.0 years.

RESULTS

• ? The 8‐year overall survival (OS) of the study population was 85.1%.
• ? The 8‐year OS for IIEF‐6scores ≤12, 13–23 and 24–30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001).
• ? Cardiovascular events accounted for a significant portion of deaths in each IIEF‐6 group.
• ? When combined with other risk factors for cardiovascular disease, an IIEF‐6 score of ≤12 had an additive effect on all‐cause mortality (IIEF‐6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%).

CONCLUSIONS

• ? A pre‐implant IIEF‐6score of ≤12 was associated with a higher incidence of all‐cause mortality.
• ? Pre‐treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients.
• ? Aggressive treatment of medical co‐morbidity is warranted to impactOS.

     

Comparison of impact of monopolar versus bipolar resection of the prostate on erectile function in patients with benign hyperplasia of the prostate

Introduction and Objective

The incidence of erectile dysfunction (ED) after TURP for BPH is still debated. Current study aims at comparing the impact of monopolar and bipolar TURP on the sexual function of male patients with LUTS, using the IIEF EF-domain score (questions 1–5, 15) and to identify statistical risk factors associated with development of post-operative ED.

An open-label, multicentre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy

Associate Editor Michael G. Wylie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVES

To compare treatment preference, efficacy, and tolerability of sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction (ED) in men naïve to phosphodiesterase 5 (PDE5) inhibitor therapy.

PATIENTS AND METHODS

This was an open‐label, crossover study of sildenafil and tadalafil (taken as needed). After a 4‐week baseline assessment, 367 men with ED (mean age 54 years) were randomized to receive sildenafil for 12 weeks followed by tadalafil for 12 weeks or vice versa (8‐week dose optimization and 4‐week assessment phases). During dose optimization, patients started taking 25‐ or 50‐mg sildenafil or 10‐mg tadalafil and could titrate to find their optimum dose (25‐, 50‐ or 100‐mg sildenafil; 10‐ or 20‐mg tadalafil). After completing both 12‐week periods, patients chose which treatment to continue during an 8‐week extension. Efficacy was measured with the International Index of Erectile Function (IIEF) and Sexual Encounter Profile (SEP) diary.

RESULTS

Of the 291 men who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose tadalafil (P < 0.001) for the 8‐week extension. The IIEF erectile function domain scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient percentage success scores for SEP2 (penetration) were: baseline (46%), sildenafil (post‐baseline 82%) and tadalafil (post‐baseline 85%; P = 0.06, sildenafil vs tadalafil), and for SEP3 (successful intercourse) were: baseline (19%), sildenafil (post‐baseline 72%), and tadalafil (post‐baseline 77%; P = 0.003, sildenafil vs tadalafil). The only treatment‐emergent adverse events that were reported by >5% of men were headache and flushing.

CONCLUSIONS

In men with ED who were naïve to PDE5 inhibitor therapy, sildenafil and tadalafil were both effective and well tolerated. After treatment with sildenafil and tadalafil, 29% of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8‐week extension.

     

Investigation of a complex plant extract for mild to moderate erectile dysfunction in a randomized,double‐blind,placebo‐controlled,parallel‐arm study

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

OBJECTIVE

To assess the effects of a complex plant extract (Prelox®, a formulation of pine bark extract and l ‐arginine aspartate; Horphag Research UK Ltd, London, UK) on erectile dysfunction (ED) in men, as sexual desire typically persists in ageing men, while their erectile and endothelial function gradually declines.

PATIENTS AND METHODS

In this double‐blind, placebo‐controlled study we assessed the effects of Prelox in 124 patients (aged 30–50 years) with moderate ED over an investigational period of 6 months. The International Index Of Erectile Function (IIEF) was used to quantify changes in sexual function.

RESULTS

The erectile domain of the IIEF (questions 1–5 plus 15) improved with Prelox from a baseline mean (sd ) score of 15.2 (6.6) to 25.2 (2.1) after 3 months and 27.1 (2.1) after 6 months of treatment. In the placebo group there was an increase from a baseline score of 15.1 (7.0) to 19.1 (3.0) and 19.0 (3.1) after 3 and 6 months, respectively. The effects with Prelox were statistically significant compared with placebo (P < 0.05). Mean (sd ) total plasma testosterone levels increased significantly from 15.9 (2.3) to 18.9 (2.6) nmol/L (P < 0.05) after 6 months with Prelox, compared to an increase from 16.9 (2.4) to 17.3 (2.3) nmol/L in the placebo group.

CONCLUSION

This study shows that Prelox is effective for improving erectile function, and that this effect persists on continuous therapy for up to 6 months. Moreover, there is some evidence that erectile function continues to improve the longer the therapy is used.     

Combination of intralesional verapamil and oral antioxidants for Peyronie's disease: a prospective,randomised controlled study

The aim of this study was to evaluate the efficacy of the association of intralesional verapamil (ILV) injection with oral antioxidants compared with ILV monotherapy in patients with early onset of Peyronie's disease (PD) at 12‐week follow‐up. Group A (n = 52) received ILV 10 mg weekly for 12 weeks, while group B (n = 53) received ILV 10 mg weekly for 12 weeks + antioxidants orally one tablet once a day for 3 months. The main efficacy outcomes were the change in plaque size (PS), penile curvature (PC), visual analogue score (VAS), IIEF‐15 and IIEF‐15 subdomains. Both groups showed significant improvement from baseline to week 12 relative to PS and PC, while group B also in IIEF‐15 score (mean difference: 5.51, P < 0.01) and VAS (mean difference: ?2.71, P < 0.01). No significant differences were observed between both groups in PS and PC. Finally, both groups showed significant increase in orgasmic function (IIEF‐OF) and overall satisfaction (IIEF‐OS), while group B showed significant improvement also in intercourse satisfaction (IIEF‐IS). Significant differences were found relative to IIEF‐OF, IIEF‐IS, IIEF‐OS and VAS scores in the group B compared with group A. Patients affected by PD may benefit from combination treatment with ILV and oral antioxidants thanks to the improvement in IIEF‐OF, IIEF‐IS and IIEF‐OS at 12 weeks.     

Urokinase‐plasminogen‐activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer

OBJECTIVE

To evaluate the expression of urokinase‐plasminogen‐activator receptor (uPA‐R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis.

PATIENTS AND METHODS

In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA‐R expression was detected by dual‐immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow‐up was initiated to detect tumour relapse (defined as a prostate‐specific antigen (PSA) level of ≥0.2 ng/mL).

RESULTS

Overall, there was expression of ‘CK + uPA‐R’ in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high‐risk cancer (P = 0.005). The relative risk for CK + uPA‐R expression in the BM was 3.1 times higher in high‐risk than in low‐risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA‐R expression in BM or PB. The PSA‐recurrence free survival was significantly lower in patients with CK + uPA‐R‐positive BM cells (P = 0.01).

CONCLUSION

In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high‐risk disease. All patients with a later PSA relapse had had uPA‐R expression in their DTC from the BM. DTC with uPA‐R expression was an adverse prognostic factor for prostate cancer.     

Impact of previous mesh hernia repair on the performance of open radical prostatectomy – complications and functional outcome

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

OBJECTIVES

To determine the impact of previous inguinal mesh hernia repair (IMHR) on the performance of subsequent open radical retropubic prostatectomy (ORRP).

PATIENTS AND METHODS

A total of 1466 patients underwent ORRP for clinically localized prostate cancer from 2004 to 2008; 51 patients (3.5%) presented with a history of IMHR. Body‐mass index (BMI), perioperative blood loss (PBL), operating time (OT), performance of pelvic lymph node dissection (PLD), positive resection‐margins (R1), continence and potency between the groups were analysed using Mann–Whitney U and χ² tests.

RESULTS

Fifty‐one patients with previous IMHR were compared with 1466 patients without previous mesh implantation (nMI) who underwent ORRP. Mean age was 66.8 years and mean BMI 25.7. No statistically difference in the mean OT (68 vs 72 min, P= 0.112), mean PBL (167 vs 156 ml, P= 0.089) or R1 was observed in the pT2‐stage tumors (3% vs 9.7%, P= 0.197), or in the pT3‐stage tumors (16% vs 21%, P= 0.386). After 3 months 85% showed full continence in the nMI group vs 83.9% MI group (P= 0.864) and after 12 months 94.5% of the nMI patients vs 97.6% with mesh (P= 0.610). The IIEF‐5 score after 3 months showed a median of 9.0 in the MI group and 4.5 in the nMI group (P= 0.116) and after 12 months 12.0 in the MI group and 9.0 in the nMI group (P= 0.511). PLD was significantly more feasible in patients that underwent only unilateral IMHR compared with bilateral IMHR (96% vs 40%, P= 0.001) and significantly less feasible if previous IMHR was operated laparoscopically than with an open access (47% vs 88%, P= 0.014).

CONCLUSION

No impairment of perioperative variables or functional outcome during ORRP was observed in patients with IMHR. PLD could be performed in a significantly fewer patients who underwent bilateral IMHR or laparoscopic IMHR.     

Androgen deprivation therapy before radical prostatectomy is associated with poorer postoperative erectile function outcomes

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Erectile dysfunction is a recognized complication of radical prostatectomy. Androgen deprivation therapy adversely impacts sexual function. Our study shows that the preoperative use of androgen deprivation therapy significantly reduces erectile function recovery after radical prostatectomy. The underneath pathophysiological mechanisms for this to occur are reviewed.

OBJECTIVE

• ? To define the impact of androgen deprivation therapy (ADT), undergone before radical prostatectomy (RP), on erectile function (EF) recovery.

MATERIAL AND METHODS

• ? A total of 38 consecutive patients presenting to a sexual medicine clinic after undergoing RP who had received ADT before RP (ADT+ group) were compared with a contemporary, age and comorbidity‐matched cohort of 94 patients who did not receive ADT (ADT‐ group) before undergoing RP.
• ? Medical records were reviewed for demographics, comorbidity profiles and duration of ADT exposure.
• ? All the patients underwent Doppler penile ultrasonography within 6 months of RP and were administered the International Index of Erectile Function (IIEF) questionnaire.
• ? All the patients underwent evaluation of EF recovery. We analysed the incidence of venous leak (VL), mean IIEF EF domain score and proportion of men with EF domain scores ≥24 at 18 months after RP.

RESULTS

• ? The mean age, comorbidity profiles, median Gleason score, median pre‐treatment PSA level, and mean time to evaluation after RP were similar between the two groups.
• ? The median duration of ADT exposure in the ADT+ group was 3 months.
• ? The incidence of VL within 6 months of surgery was 60% for the ADT+ and 20% for the ADT‐ group (P < 0.001). Likewise, the IIEF EF domain scores and proportion of men with EF domain scores ≥24 at 18 months were significantly lower in the ADT+ group, even when controlled for nerve‐sparing status.

CONCLUSION

• ? Our data suggest that preoperative use of ADT adversely impacts EF outcomes and should therefore be avoided in the absence of robust data suggesting any oncological benefit.

     

The effect of Gleason score on the predictive value of prostate‐specific antigen doubling time

Study Type – Prognosis (individual cohort series)
Level of Evidence 2b

OBJECTIVE

To evaluate the influence of the pathological Gleason score on the predictive value of the prostate‐specific antigen (PSA) doubling time (DT), as this variable predicts a patient’s risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production.

PATIENTS AND METHODS

We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer‐specific survival (CSS) rates were estimated using the Kaplan‐Meier method and Cox proportional hazard regression models.

RESULTS

A PSA DT of <18 vs >18 months predicted a lower 10‐year systemic progression‐free survival for patients with tumours having a pathological Gleason score of <7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8–10 (57% vs 73%, P = 0.042). A PSA DT after RP of <12 months was significantly associated with a lower 10‐year systemic progression‐free survival for patients with tumours having a Gleason score of <7 (77% vs 94%, P < 0.001) and 7 (61% vs 86%, P < 0.001), but not 8–10 (61% vs 75%, P = 0.11). The ability of PSA DT before and after RP to predict systemic progression and CSS decreased with increasing Gleason score.

CONCLUSIONS

The PSA DT remains associated with outcome both before and after RP across increasing pathological Gleason scores, although the predictive ability of PSA DT is diminished in Gleason 8–10 cancers.     

A Comparative Study of Voiding and Sexual Function after Total Mesorectal Excision with Autonomic Nerve Preservation for Rectal Cancer: Laparoscopic Versus Robotic Surgery

Purpose

To evaluate the protection of the urogenital function after robot-assisted total mesorectal excision (R-TME) for rectal cancer compared to those of laparoscopic TME (L-TME).

Methods

69 patients who underwent L-TME (n?=?39) or R-TME (n?=?30) were prospectively enrolled. Their urogenital function was evaluated by uroflowmetry, a standard questionnaire of the international prostate symptom score (IPSS) and the international index of erectile function (IIEF) before surgery and 1, 3, 6, and 12?months after surgery. The pre- and postoperative IPSS and IIEF scores were compared to detect functional deterioration by paired t test for each group. How postoperative IPSS and IIEF scores and uroflowmetry data deviated from the preoperative values (??) were statistically compared between the two groups.

Results

The IPSS score significantly increased 1?month after surgery; the recovery from decreased urinary function took 6?months for patients in the L-TME group (8.2?±?6.3; P?=?0.908) but 3?months in the R-TME group (8.36?±?5.5; P?=?0.075). The ??IPSS scores were significantly different between the two groups at 3?months (P?=?0.036). In male patients (L-TME 20, R-TME 18), the total IIEF score in R-TME and L-TME significantly decreased 1?month after surgery, L-TME gradually recovered over 12?months (46.00?±?16.9; P?=?0.269), but R-TME recovered within 6?months (44.61?±?13.76; P?=?0.067). The ??IIEF score value was not significantly different at any time between the two groups, but in an itemized analysis of the change in erectile function and sexual desire, there were significant differences at 3?months between the two groups.

Conclusions

R-TME for rectal cancer is associated with earlier recovery of normal voiding and sexual function compared to patients who underwent L-TME, although this result needs to be verified by larger prospective comparative studies.     

Does hormonal manipulation in conjunction with permanent interstitial brachytherapy,with or without supplemental external beam irradiation,improve the biochemical outcome for men with intermediate or high‐risk prostate cancer?

OBJECTIVE

To determine whether hormonal manipulation improves the biochemical outcome for men with intermediate or high‐risk prostate cancer and undergoing permanent brachytherapy with or without supplemental external beam radiation therapy.

PATIENTS AND METHODS

From April 1995 to August 2000, 350 patients with intermediate‐risk (225 men; a Gleason score of ≥ 7 or a prostate specific antigen, PSA, level of ≥ 10 ng/mL or clinical stage ≥ T2b) or high‐risk features (125 men; two or three of a Gleason score of ≥ 7 or PSA ≥ 10 ng/mL or clinical stage ≥ T2b) underwent transperineal ultrasonography‐guided permanent brachytherapy. No patient underwent pathological lymph node staging. Of these patients, 293 received supplemental external beam radiation therapy (EBRT), 141 received hormonal manipulation, with 82 having hormonal therapy for ≤ 4 months (median 4) for cytoreduction, while 59 had neoadjuvant and adjuvant hormonal manipulation (median 8 and 12 months for intermediate‐ and high‐risk, respectively). The median patient age was 68.5 years. No patient was lost to follow‐up. The mean (sd ) and median follow‐up was 50 (18) and 49 months (calculated from the day of implantation). Biochemical disease‐free (BDF) survival was defined using a consensus definition. The clinical variables evaluated for BDF survival included risk group, Gleason score, patient age, clinical T‐stage and pretreatment PSA. Treatment variables included use of hormonal manipulation stratified into cytoreductive (≤ 4 months) vs adjuvant (> 4 months) regimens, supplemental EBRT, isotope and dosimetric variables.

RESULTS

For intermediate‐risk patients, the 6‐year actuarial BDF survival rates were 98%, 96% and 100% for hormone naïve, cytoreductive and adjuvant treatment, respectively (P = 0.693); for high‐risk patients the respective values were 79%, 94% and 92% (P = 0.046). When stratified by pretreatment PSA, hormonal manipulation improved the outcome for patients with a PSA of ≥ 10 ng/mL (P = 0.019), but not for those with < 10 ng/mL (P = 0.661). Hormonal status was not statistically significant in predicting biochemical outcome when stratified by Gleason score. The follow‐up in hormone‐naïve patients was significantly longer than that in hormonally manipulated patients, at 55 (20) vs 43 (15) months (P < 0.001). In a multivariate analysis only the Gleason score predicted failure in intermediate‐risk patients, while pretreatment PSA, the use of hormonal manipulation and Gleason score predicted the outcome in high‐risk patients (P = 0.035). For both hormone‐naïve and hormonally manipulated BDF patients, the median PSA level after implantation was < 0.1 ng/mL.

CONCLUSION

In patients treated by permanent prostate brachytherapy, hormonal manipulation improved the biochemical outcome for those at high‐risk and those with an initial PSA of ≥ 10 ng/mL, but not for those with intermediate‐risk features. The use of hormonal therapy for> 4 months conferred no additional biochemical advantage over short‐course regimens. Because the follow‐up in hormone‐naïve patients was longer than that for those receiving hormonal manipulation, additional follow‐up will be mandatory to confirm the durability of these findings.

     

Analysis of association between the 5‐HTTLPR and STin2 polymorphisms in the serotonin‐transporter gene and clinical response to a selective serotonin reuptake inhibitor (sertraline) in patients with premature ejaculation

Study Type – Therapy (cohort)
Level of Evidence 2b

OBJECTIVE

To test the hypothesis that polymorphism within the gene‐linked polymorphic region (5‐HTTLPR) and second intron of SLC6A4 gene (STin2) is associated with selective serotonin‐reuptake inhibitors (SSRIs) response in subjects with premature ejaculation (PE).

PATIENTS AND METHODS

In all, 246 men with PE were recruited in this study. They were asked to take sertraline 50 mg daily for 2 weeks, and thereafter 100 mg daily, for a 12‐week treatment period. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IELT), and International Index of Erectile Function (IIEF). The efficacy of treatment was assessed using responses to IIEF, and geometric mean IELT evaluation. 5‐HTTLPR was genotyped using polymerase chain reaction techniques. A repeated‐measures analysis of variance of geometric mean IELT was done to test a genotype effect on treatment outcome with SSRI (sertraline).

RESULTS

Of 227 participants who completed the study, 175 (77.1%) responded to sertraline (IELT >1 min). Overall the patients had a 3.7‐fold (95% confidence interval, CI, 1.72–5.46) increase of the geometric mean IELT (P = 0.001). The results showed that responses were significantly better for the L_A/L_A genotype of the 5‐HTTLPR polymorphism than for S‐allele carriers (P = 0.001). The STin2 12/12 genotype was found more often in those responding to sertraline than in those not responding (P = 0.001). The probability of patients responding sufficiently to sertraline with an L_A/L_A genotype was highest (odds ratio 4.66, 95% CI, 2.48–6.14).

CONCLUSIONS

These findings indicate that the genotype of 5‐HTT contributes in unique ways to the variation in the outcome of PE treatment with SSRIs.