Basic principles of anatomy for optimal surgical treatment of prostate cancer

The treatment of prostate cancer (PCa) with nerve sparing radical prostatectomy (NSRP) has experienced a substantial improvement in recent years due to new insights in anatomy of the prostate and of the adjacent structures. Knowledge of this specific anatomy is mandatory during RP in order to avoid injuries to functional tissue. Above all, these tissues are the neurovascular bundle (NVB) and the urethral sphincter. We therefore reviewed the available literature on prostatic anatomy and summarized it in this article. A search of the PubMed database was performed using the keywords radical prostatectomy, anatomy, neurovascular bundle, fascia, pelvis and sphincter. Relevant articles were reviewed, analyzed and summarized. This article gives an insight in the anatomy of the NVB, the urethral sphincter and the fascias surrounding the prostate. The NVB might be hampered near the seminal vesicles, at the lateral surface of the prostate and in the area of the prostato-urethral junction. The urethral sphincter might be hampered during dissection of the dorsal vein complex and during dissection of the urethra at the prostatic apex. Finally, the anatomy of the fascias surrounding the prostate is complex and can inter-individually vary substantially, which adds to the technical difficulties of NSRP. With this article we provide an overview on the complex anatomy of the prostate and the adjacent tissues. Respecting and considering these anatomic principles during NSRP should result in good postoperative functional outcome, as well as in good outcome in cancer control.     

Baseline Potency in Candidates for Bilateral Nerve-Sparing Radical Retropubic Prostatectomy

Objectives

To assess the baseline erectile function (EF) of patients with clinically localized prostate cancer (pCa), who are candidates for a bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP) to (a) objectively rate the preoperative self-reported subjective patient's EF and (b) investigate possible correlations between preoperative EF and demographic data and comorbidities.

Materials and methods

Two-hundred-thirty-four patients, who verbally self-reported they were preoperatively fully potent and strongly motivated to maintain postoperative EF, underwent a BNSRRP. A comprehensive medical and sexual history was obtained on hospital admission the day prior to surgery. Subjectively reported potency rate was compared with the scores of the International Index of Erectile Function (IIEF).

Results

The EF domain of the IIEF showed a baseline normal EF in only 43% of the subjects. In contrast, 13% had a mild erectile dysfunction (ED), 8% had a mild to moderate ED, 8% complained of a moderate ED, and as many as 28% reported severe EF impairment. Interestingly, 38% of the patients with severe ED did not attempt any intercourse during the last 4 weeks prior to surgery.

Conclusions

A significant proportion of patients with clinically localized pCa and self-reported total potency already had suffered from ED preoperatively. Incorrect timing of questionnaires administration, the potential influence of preoperative patient's psychological distress, and the implication of the patient's partner's psychological and sexual health may be contributing factors to the contradictory finding. The preoperative use of validated questionnaire may help to identify patients who can actually expect to regain potency following a BNSRRP.     

经腹膜外途径腹腔镜前列腺癌根治术中尿控技巧探讨

目的回顾性总结探讨经腹膜外途径腹腔镜下前列腺癌根治术中处理尿控的方法及技巧。方法临床选择T1～T3a前列腺癌患者44例,年龄为58～82岁,平均年龄为70.5岁。术前前列腺总特异性抗原(TPSA)为8.9～38.6 ng/ml。所有患者术前均行经直肠前列腺穿刺活检,病理明确诊断证实为前列腺癌,平均Gleason评分(5.6±2.5)分,44例患者均行经腹膜外途径腹腔镜下前列腺癌根治术。结果 44例患者均顺利完成手术,手术时间150～410分钟,平均手术时间(220±85)分钟;术中出血量300～1500ml,平均(400±220)ml;术后完全尿控33例(75.0%),部分尿控9例(20.5%)(1周后恢复),完全性尿失禁2例(4.5%)(持续3个月以上),术后病理切缘阳性6例(13.6%);直肠损伤1例,经保守治疗治愈。结论腹腔镜下前列腺癌根治术治疗局限性前列腺癌安全、有效,术后尿控效果与术中神经血管束(NVB)、远端尿道保留长度、正确处理膀胱颈部、膀胱尿道吻合的技巧处理及术者的经验相关。     

High Chance of Late Recovery of Urinary and Erectile Function Beyond 12 Months After Radical Prostatectomy

Urinary incontinence (UI) and erectile dysfunction (ED) after radical prostatectomy (RP) can impose a strong burden. While most studies focus on certain time points after RP when analyzing functional outcome, there is paucity of evidence on late functional recovery in patients with UI or ED at 12 mo after RP. Using longitudinal patient data from a large European single-center, we show that the chance of regaining continence among patients (n = 974) with UI (≥1 pad/24 h) at 12 mo after RP was 38.6% after 24 mo and 49.7% after 36 mo. The corresponding rates for patients (n = 1115) with ED (defined as International Index of Erectile Function-5 score <18) at 12 mo after RP were 30.8% at 24 mo and 36.5% at 36 mo after RP. Patients with postoperative UI or ED 12 mo after RP should be counseled about their good chance of achieving continence or potency in the course of time.

Predictive and Prognostic Models in Radical Prostatectomy Candidates: A Critical Analysis of the Literature

Context

Numerous predictive and prognostic tools have recently been developed for risk stratification of prostate cancer (PCa) patients who are candidates for or have been treated with radical prostatectomy (RP).

Objective

To critically review the currently available predictive and prognostic tools for RP patients and to describe the criteria that should be applied in selecting the most accurate and appropriate tool for a given clinical scenario.

Evidence acquisition

A review of the literature was performed using the Medline, Scopus, and Web of Science databases. Relevant reports published between 1996 and January 2010 identified using the keywords prostate cancer, radical prostatectomy, predictive tools, predictive models, and nomograms were critically reviewed and summarised.

Evidence synthesis

We identified 16 predictive and 22 prognostic validated tools that address a variety of end points related to RP. The majority of tools are prediction models, while a few consist of risk-stratification schemes. Regardless of their format, the tools can be distinguished as preoperative or postoperative. Preoperative tools focus on either predicting pathologic tumour characteristics or assessing the probability of biochemical recurrence (BCR) after RP. Postoperative tools focus on cancer control outcomes (BCR, metastatic progression, PCa-specific mortality [PCSM], overall mortality). Finally, a novel category of tools focuses on functional outcomes. Prediction tools have shown better performance in outcome prediction than the opinions of expert clinicians. The use of these tools in clinical decision-making provides more accurate and highly reproducible estimates of the outcome of interest. Efforts are still needed to improve the available tools’ accuracy and to provide more evidence to further justify their routine use in clinical practice. In addition, prediction tools should be externally validated in independent cohorts before they are applied to different patient populations.

Conclusions

Predictive and prognostic tools represent valuable aids that are meant to consistently and accurately provide most evidence-based estimates of the end points of interest. More accurate, flexible, and easily accessible tools are needed to simplify the practical task of prediction.     

Combined reporting of cancer control and functional results of radical prostatectomy

INTRODUCTION: The results of radical prostatectomy (cancer control, continence and sexual potency) are currently presented separately, while the success of this surgery depends on a combination of good cancer control with maintenance of continence and erections. We propose a score to jointly evaluate and report cancer control and functional results. METHODS: The results of 205 radical prostatectomies were studied at one year. Cancer control was evaluated by PSA. Continence and sexual potency were evaluated by a self-administered questionnaire. Each patient was attributed 0 or 4 points according to the presence of absence of biochemical progression (PSA>0.2 ng/ml), 0 or 2 points according to the presence or absence of urinary incontinence (use of pads) and 0 or 1 point according to the presence or absence of impotence (no erections). The sum of these points provided a score classifying the patient into 8 distinct categories, from 0 to 7, each corresponding to a specific status (from 0 (0+0+0): no cancer control-incontinence-impotence to 7 (4+2+1): cancer control-continence-sexual potency). RESULTS: One year after the operation, 175 (85%) of patients had a PSA less than 0.2 ng/ml, 135 (65.8%) were continent and 64 (32.7%) reported erections. All patients with a score > or =4 had good cancer control, with no functional disorders for a score of 7 (4+2+1) (20%), no disorders of continence for a score of 6 (4+2+0) (31.5%), no disorders of erection for a score of 5 (4+0+1) (8.3%), or with incontinence and impotence for a score of 4 (4+0+0) (21.9%). All patients with a score <4 had a PSA>0.2 ng/ml, but with no functional disorders for a score of 3 (0+2+1) (2.4%), no incontinence for a score of 2 (0+2+0) (8.3%), and no impotence for a score of 1 (0+0+1) (1.9%). 1.9% of patients were incontinent, impotent and showed signs of biochemical progression (score 0=0+0+0). CONCLUSION: This score allows analysis of the global (cancer control and functional) results of radical prostatectomy and would facilitate comparisons between various surgical techniques (type of approach, nerve-sparing techniques) and various centres.     

Costs of Radical Prostatectomy for Prostate Cancer: A Systematic Review

ContextRobot-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted as a new approach for radical prostatectomy (RP) in patients with prostate cancer (PCa). The use of new technology may increase costs for RP.ObjectiveTo summarize data on direct costs of various approaches to RP and to discuss the consequences of cost differences.Evidence acquisitionA systematic literature search was performed in March 2012 using the PubMed, Web of Science, and Cochrane Library databases. A complex search strategy was applied. Articles were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Articles reporting on direct costs of RP (open retropubic [RRP], radical perineal [RPP], laparoscopic [LRP], RALP) in men with clinically localized PCa were eligible for study inclusion.Evidence synthesisOf 1218 articles initially screened by title, the multistep, systematic search identified 11 studies presenting direct costs of different approaches to RP. Of the 11 studies, 7 compared the costs of different RP approaches. Minimally invasive RP (MIRP) (ie, LRP or RALP) was more expensive than RRP in most studies, mainly due to increased surgical instrumentation costs. In the comparative studies, costs ranged from (in US dollars) $5058 to $11 806 for MIRP and from $4075 to $6296 for RRP, with RALP having the highest direct costs. In one study applying standardized, health economic-evaluation criteria, RALP was not found to be cost effective. Limitations of this review include significant differences in observational study designs and an absence of prospective comparative studies. Moreover, there are limited post-RP data on the costs of adjuvant treatments and other health care–related expenses after PCa surgery.ConclusionsFew studies compared direct costs of different approaches to RP. The use of new technology, particularly RALP, results in added costs for the procedure. Cost effectiveness of new technologies should be assessed before widespread adoption. To date, in the lone study to evaluate this, RALP was not found to be cost effective from a health care, economic standpoint. However, longer follow-up of patients is required to better evaluate its impact on overall costs and quality of PCa care.     

Are We Improving Erectile Function Recovery After Radical Prostatectomy? Analysis of Patients Treated over the Last Decade

Background

The last decade has seen several advances in radical prostatectomy (RP) technique and post-RP care that are relevant to erectile function (EF) recovery.

Multi-institutional Validation of the CAPRA-S Score to Predict Disease Recurrence and Mortality After Radical Prostatectomy

Background

The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally.

Objective

To validate CAPRA-S in a large, multi-institutional, external database.

Design, setting, and participants

The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670 men (92%) had complete data to calculate a CAPRA-S score.

Intervention

RP.

Outcome measurements and statistical analysis

The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index.

Results and limitations

The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0–2, 3–5, and 6–10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The c-index for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events.

Conclusions

In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index >0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy.     

External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis

Background

Long-term survival can be achieved in patients affected by localized prostate cancer (PCa) treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). However, development of a second primary tumor is still poorly investigated.

Open radical retropubic prostatectomy using high anterior release of the levator fascia and constant haptic feedback in bilateral neurovascular bundle preservation plus early postoperative phosphodiesterase type 5 inhibition: a contemporary series

Background

Patients with newly diagnosed localized prostate cancer who choose surgery want cure and decent quality of life, namely, pad-free urinary control and, often, erectile function satisfactory for sexual intercourse.

Objective

Determine in a prospective study the positive surgical margin rate and functional outcomes for a consecutive series of patients undergoing open radical retropubic prostatectomy (ORRP) with bilateral neurovascular bundle preservation (BNVBP) performed by one experienced surgeon.

Design, setting, and participants

Of 197 consecutive patients undergoing BNVBP during 2008, 123 were evaluable, allowing both immediate postoperative phosphodiesterase type 5 inhibition (PDE5i) and a third-party questionnaire with validated urinary and erectile function domains provided preoperatively and at 3, 6, and 12 mo postoperatively.

Intervention

Two interventions were used: (1) ORRP with ×4.3 optical loupes and constant digital tactile monitoring during BNVBP preceded by high anterior release (HAR) of levator fascia and neurovascular bundles and (2) early postoperative PDE5i.

Measurements

Age; biopsy Gleason score; clinical stage; preoperative prostate-specific antigen level; pathologic grade; stage; margin status; University of California, Los Angeles Prostate Cancer Index domain for urinary pad use and bother; and International Index of Erectile Function-5 (IIEF-5) were used.

Results and limitations

Surgical margins were positive in 1 of the 123 evaluable patients (1%). At 1 yr, 95% of patients were pad-free. Satisfactory erectile function was achieved by 109 patients (89%): 82 (67%) scored an IIEF-5 of 22–25, and 27 (22%) scored <22–25 with ≥4 on either satisfaction or confidence questions or achieved “full” erection within the first year. Mean hospital stay was 1.3 d. Limitations were (1) observational, noncomparative, single-surgeon series and (2) in third-party methodology, failure to capture patient answers for all questionnaire intervals with resultant inability to address durability of functional results for all patients.

Conclusions

ORRP using ×4.3 optical loupe magnification, constant haptic feedback in BNVBP with HAR, and immediate postoperative PDE5i yielded satisfactory outcomes.     

Long-term Distress After Radical Prostatectomy Versus Watchful Waiting in Prostate Cancer: A Longitudinal Study from the Scandinavian Prostate Cancer Group-4 Randomized Clinical Trial

Background

Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups.

Objective

To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally.

Design, setting, and participants

The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up.

Intervention

RP compared with WW.

Outcome measurements and statistical analysis

A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model.

Results and limitations

Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30–40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook.

Conclusions

Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management.     

Retropubic,Laparoscopic, and Robot-Assisted Radical Prostatectomy: A Systematic Review and Cumulative Analysis of Comparative Studies

Context

Despite the wide diffusion of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP), only few studies comparing the results of these techniques with the retropubic radical prostatectomy (RRP) are currently available.

Objective

To evaluate the perioperative, functional, and oncologic results in the comparative studies evaluating RRP, LRP, and RALP.

Evidence acquisition

A systematic review of the literature was performed in January 2008, searching Medline, Embase, and Web of Science databases. A “free-text” protocol using the term radical prostatectomy was applied. Some 4000 records were retrieved from the Medline database; 2265 records were retrieved from the Embase database;, and 4219 records were retrieved from the Web of Science database. Three of the authors reviewed the records to identify comparative studies. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK).

Evidence synthesis

Thirty-seven comparative studies were identified in the literature search, including a single, randomised, controlled trial.With regard to the perioperative outcome, LRP and RALP were more time consuming than RRP, especially in the initial steps of the learning curve, but blood loss, transfusion rates, catheterisation time, hospitalisation duration, and complication rates all favoured LRP. With regard to the functional results, LRP and RRP showed similar continence and potency rates. Similarly, no significant differences were identified between LRP and RALP, while a single, nonrandomised, prospective study suggested advantages in terms of both continence and potency recovery after RALP, compared with RRP. With regard to the oncologic outcome, LRP and RALP were associated with positive surgical margin rates similar to those of RRP.

Conclusions

The quality of the available comparative studies was not excellent. LRP and RALP are followed by significantly lower blood loss and transfusion rates, but the available data were not sufficient to prove the superiority of any surgical approach in terms of functional and oncologic outcomes. Further high-quality, prospective, multicentre, comparative studies are needed.     

Evaluation of early pelvic floor physiotherapy on the duration and degree of urinary incontinence after radical retropubic prostatectomy in a non-teaching hospital

The objective of this study was to study the effect of early pelvic floor re-education on the degree and duration of incontinence and to evaluate the results of radical retropubic prostatectomy (RRP) performed in a non-teaching hospital. This is a non-randomised study. From March 2000 to November 2003, 57 consecutive men, who underwent RRP for localized prostate cancer, participated in a pelvic floor re-educating program. Continence was defined as a loss of no more than 2-g urine on the 24-h pad test and no use of pads. The 24-h pad test was performed once in every 4 weeks until the patient indicated that he was continent. Diurnal and nocturnal continence was achieved after 1, 2, 3, 6 and 12 months post catheter removal in 40, 49, 70, 86 and 88% of all men, respectively. Comparison of our results with current literature suggest that the time period towards continence after a RRP can be shortened relevantly if pelvic floor re-education is started directly after catheter removal.     

Significance of the Percentage of Prostate Needle Biopsy Cores with Cancer as a Predictor of Disease Extension in Radical Prostatectomy Specimens in Japanese Men

Objectives: To evaluate the significance of the percent of positive biopsy cores (PPBC) with cancer, which has been shown to be one of the most useful predictors of prostate cancer extension in patients undergoing radical prostatectomy. Materials and methods: This study included 120 patients who underwent radical prostatectomy for prostate cancer without any neoadjuvant therapies. All of these patients were diagnosed by random prostate biopsy targeting 8 cores; that is, standard sextant cores and 2 additional cores from the bilateral anterior lateral horns. We evaluated the appropriate cut-off points of PPBC for predicting disease extension according to the number of biopsy cores. Based on these criteria, multivariate analysis was then performed to determine whether PPBC could be an independent factor differentiating organ-confined disease from extraprostatic disease. Results: The most suitable PPBC cut-off value using findings targeting 8 cores for predicting disease extension was 37.5%. If PPBC was calculated based on the outcome of standard sextant cores alone, it is most appropriate to use 33.3% as the cut-off point. Multivariate analysis showed that PPBC calculated based on the standard sextant cores and percent of cancer in the biopsy set could be used as independent factors predicting disease extension irrespective of other biopsy-associated factors. Conclusions: For predicting disease extension, it may be useful to calculate PPBC based on the outcomes of standard sextant biopsy cores alone even if additional cores were taken, and that PPBC calculated in such a way may be the strongest preoperative predictor of prostate cancer extension in Japanese men scheduled for radical prostatectomy.     

Pelvic Lymph Node Dissection During Robot-assisted Radical Prostatectomy: Efficacy,Limitations, and Complications—A Systematic Review of the Literature

Context

Pelvic lymph node dissection (PLND) in prostate cancer is the most effective method for detecting lymph node metastases. However, a decline in the rate of PLND during radical prostatectomy (RP) has been noted. This is likely the result of prostate cancer stage migration in the prostate-specific antigen-screening era, and the introduction of minimally invasive approaches such as robot-assisted radical prostatectomy (RARP).

Objective

To assess the efficacy, limitations, and complications of PLND during RARP.

Evidence acquisition

A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1990 to December 2012. The literature search used the following terms: prostate cancer, radical prostatectomy, robot-assisted, and lymph node dissection.

Evidence synthesis

The median value of nodal yield at PLND during RARP ranged from 3 to 24 nodes. As seen in open and laparoscopic RP series, the lymph node positivity rate increased with the extent of dissection during RARP. Overall, PLND-only related complications are rare. The most frequent complication after PLND is symptomatic pelvic lymphocele, with occurrence ranging from 0% to 8% of cases. The rate of PLND-associated grade 3–4 complications ranged from 0% to 5%. PLND is associated with increased operative time. Available data suggest equivalence of PLND between RARP and other surgical approaches in terms of nodal yield, node positivity, and intraoperative and postoperative complications.

Conclusions

PLND during RARP can be performed effectively and safely. The overall number of nodes removed, the likelihood of node positivity, and the types and rates of complications of PLND are similar to pure laparoscopic and open retropubic procedures.     

Effects of Tadalafil Treatment on Erectile Function Recovery Following Bilateral Nerve-sparing Radical Prostatectomy: A Randomised Placebo-controlled Study (REACTT)

Background

The potential rehabilitative and protective effect of phosphodiesterase type 5 inhibitors (PDE5-Is) on penile function after nerve-sparing radical prostatectomy (NSRP) remains unclear.

Objective

The primary objective was to compare the efficacy of tadalafil 5 mg once daily and tadalafil 20 mg on demand versus placebo taken over 9 mo in improving unassisted erectile function (EF) following NSRP, as measured by the proportion of patients achieving an International Index of Erectile Function-Erectile Function domain (IIEF-EF) score ≥22 after 6-wk drug-free washout (DFW). Secondary measures included IIEF-EF, Sexual Encounter Profile question 3 (SEP-3), and penile length.

Design, setting, and participants

Randomised, double-blind, double-dummy, placebo-controlled trial in men ≤68 yr of age with adenocarcinoma of the prostate (Gleason ≤7) and normal preoperative EF who underwent NSRP at 50 centres from nine European countries and Canada.

Interventions

1:1:1 randomisation to 9 mo of treatment with tadalafil 5 mg once daily, tadalafil 20 mg on demand, or placebo followed by a 6-wk DFW and 3-mo open-label tadalafil once daily (all patients).

Outcome measurements and statistical analysis

Logistic regression, mixed-effects model for repeated measures, and analysis of covariance, adjusting for treatment, age, and country, were applied to IIEF-EF scores ≥22, SEP-3, and penile length.

Results and limitations

Four hundred twenty-three patients were randomised to tadalafil once daily (n = 139), on demand (n = 143), and placebo (n = 141). The mean age was 57.9 yr of age (standard deviation: 5.58 yr); 20.9%, 16.9%, and 19.1% of patients in the tadalafil once daily, on demand, and placebo groups, respectively, achieved IIEF EF scores ≥22 after DFW; odds ratios for tadalafil once daily and on demand versus placebo were 1.1 (95% confidence interval [CI], 0.6–2.1; p = 0.675) and 0.9 (95% CI, 0.5–1.7; p = 0.704). At the end of double-blind treatment (EDT), least squares (LS) mean IIEF-EF score improvement significantly exceeded the minimally clinically important difference (MCID: ΔIIEF-EF ≥4) in both tadalafil groups; for SEP-3 (MCID ≥ 23%), this was the case for tadalafil once daily only. Treatment effects versus placebo were significant for tadalafil once daily only (IIEF-EF: p = 0.016; SEP-3: p = 0.019). In all groups, IIEF-EF and SEP-3 decreased during DFW but continued to improve during open-label treatment. At month 9 (EDT), penile length loss was significantly reduced versus placebo in the tadalafil once daily group only (LS mean difference 4.1 mm; 95% CI, 0.4–7.8; p = 0.032).

Conclusions

Tadalafil once daily was most effective on drug-assisted EF in men with erectile dysfunction following NSRP, and data suggest a potential role for tadalafil once daily provided early after surgery in contributing to the recovery of EF after prostatectomy and possibly protecting from penile structural changes. Unassisted EF was not improved after cessation of active therapy for 9 mo.

Trial registration

ClinicalTrials.gov identifier NCT01026818.     

A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes

Context

The optimal management strategy for men with newly diagnosed clinically localized prostate cancer remains a matter of debate. Numerous series have reported cancer control and quality-of-life (QoL) outcomes following treatment with radical prostatectomy (RP).

Objective

Critically review published oncologic and functional outcomes after RP, and evaluate factors associated with these outcome measures.

Evidence acquisition

A review of the literature was performed using the Medline and Web of Sciences databases. Relevant reports published between 1980 and 2011 identified using the keywords prostate cancer, radical prostatectomy, prostate-specific antigen, biochemical recurrence, incontinence, and erectile dysfunction were reviewed and summarized.

Evidence synthesis

Cancer control rates following RP largely depend on the definition of treatment efficacy. While up to 40% of men have been reported to experience postoperative biochemical recurrence on long-term follow-up, death from prostate cancer has been noted in <10% of men at 15 yr after surgery in contemporary series. For men with high-risk disease, surgery affords pathologic staging, thereby facilitating the selective application of secondary therapies, and has been associated with decreased mortality risk versus radiation in retrospective series. Reported functional outcomes after surgery, particularly urinary continence and erectile dysfunction, have varied greatly to date. These assessments have been limited by nonstandardized reporting methodology. The use of robot-assisted radical prostatectomy has increased in recent years, and while follow-up is thus far short, available data do not suggest the superiority of either approach in terms of functional or oncologic outcomes.

Conclusions

RP is associated with excellent long-term cancer control. Continued efforts to conduct prospective assessments of postoperative functional outcomes are necessary using validated QoL instruments. The importance of surgical approach will also require further study, incorporating comparative oncologic, functional, and economic data.     

A Critical Analysis of the Surgical Management of Early-Stage Gallbladder Cancer in the United States

Background  Radical resection is recommended for selected patients with gallbladder (GB) cancer. We sought to determine whether radical resection improves survival for patients with early-stage cancer and to evaluate surgeon compliance with current treatment recommendations. Patients and methods  Patients with stage 0, I, or II GB cancer who underwent surgical resection were identified from the Surveillance, Epidemiology, and End Results (SEER) tumor registry from 1988 through 2004. Patients were classified by surgical procedure performed (simple vs. radical resection) and adjuvant treatment given (radiation therapy [RT] vs. no RT). Unadjusted and adjusted overall survival (OS) and cancer-specific survival (CSS) were compared. Results  Of the 4,631 patients who underwent surgery for early-stage GB cancer from 1988 through 2004, 4,188 (90.4%) underwent cholecystectomy alone and 443 (9.6%) underwent radical surgery including hepatic resection. The proportion of patients having radical surgery for T1b, T2, and T3 cancers was 4.5%, 5.6%, and 16.3%, respectively. For patients with T1b/T2 cancer, radical resection was associated with significant improvement in adjusted CSS (p = 0.01) and OS (p = 0.03). For patients with T3 cancers, we noted no improvement in CSS or OS. Survival for patients with node-positive disease (stage 2b) was universally poor and not improved by radical resection. For all patients who underwent radical resection, node negativity, female sex, age <70, low grade, and RT predicted improved CSS and OS. Conclusions  Despite a significant survival advantage for patients with T1b/T2 GB cancer who undergo radical resection, this treatment is significantly underutilized. Ensuring delivery of recommended surgical treatment is vital to improving outcomes for patients with this disease.     

Photodynamic Diagnosis Using 5-Aminolevulinic Acid for the Detection of Positive Surgical Margins during Radical Prostatectomy in Patients with Carcinoma of the Prostate: A Multicentre, Prospective, Phase 2 Trial of a Diagnostic Procedure

Background

Surgical margin status after radical prostatectomy (RP) is a significant risk factor for tumour recurrence. It is an intriguing concept to find a fluorescence marker for photodynamic diagnosis (PDD) to make tumour margins visible during surgery.

Objective

To investigate the feasibility of identification of positive surgical margins (PSM) during open retropubic or endoscopic extraperitoneal RP by 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) to enhance surgical radicality.

Design, setting, and participants

Thirty-nine patients (Gleason score 6–10, prostate-specific antigen [PSA] 2.3–120 ng/ml) received 20 mg/kg of body weight of 5-ALA orally and underwent RP (24 endoscopic extraperitoneal, 15 open retropubic).

Measurements

A PDD-suitable laparoscopy optic (Karl-Storz GmbH, Tuttlingen, Germany) with a yellow long-pass filter was coupled to a fibre-optic light cord with an excitation light source (380–420 nm, D-Light, Karl-Storz GmbH, Tuttlingen, Germany) for fluorescence excitation of PpIX and to a PDD-suitable camera for video and photo documentation by the AIDA DVD system (Karl-Storz GmbH, Tuttlingen, Germany).

Results and limitations

There were more false-negative cases in the open group (four vs two) than in the endoscopic group but more false-positive cases in the endoscopic group (two vs none) than in the open group. The overall sensitivity and specificity were 56% and 91.6%, respectively. The sensitivity of the endoscopic cases was much higher (75% vs 38%) than for the open cases, while the specificity was higher for the open group (88.2% vs 100%).

Conclusions

PDD with 5-ALA–induced PpIX during RP might be a feasible and effective method for reducing the rate of PSM. The technique seems to be more practicable during endoscopic RP rather than open RP. Further clinical studies with higher patient volumes and further development of the technique seem justified.

Trial registration

EudraCT: 2005-004406-93.