Five-year Results of a Randomized Trial Comparing Retropubic and Transobturator Midurethral Slings for Stress Incontinence

Background

Midurethral slings have become the most preferred surgical treatment for female urinary incontinence.

Objective

To compare the efficacy and safety of two midurethral sling procedures with a different technique of sling insertion 5 yr after intervention.

Design, setting, and participants

Multicenter randomized clinical trial conducted in seven public hospitals in Finland including primary cases of stress urinary incontinence.

Intervention

Surgical treatment with the retropubic tension-free vaginal tape (TVT) procedure or the transobturator tension-free vaginal tape (TVT-O) procedure.

Outcome measurements and statistical analysis

Objective treatment success criteria were a negative stress test, a negative 24-h pad test, and no retreatment for stress incontinence. Patient satisfaction was assessed by condition-specific quality-of-life questionnaires.

Results and limitations

A total of 95% of the included women could be assessed according to the protocol 5 yr after surgery. The objective cure rate was 84.7% in the TVT group and 86.2% in the TVT-O group, with no statistical difference between the groups. Subjective treatment satisfaction was 94.2% in the TVT group and 91.7% in the TVT-O group, with no difference between groups. Complication rates were low, with no difference between groups.

Conclusions

Both objective and subjective cure rates were >80% in both groups even when women lost to follow-up were included as failures. The complication rates were low, with no difference between the groups. No late-onset adverse effects of the tape material were seen.

Patient summary

Female urinary stress incontinence can be treated surgically with minimally invasive midurethral sling procedures. Two main approaches of sling placement have been developed: the retropubic and the transobturatory. We compared both approaches and followed the patients for 5 yr. We found no difference in cure rate between the procedures, and patient satisfaction was high.

Trial registration

ClinicalTrials.gov identifier NCT00379314.     

Updated Systematic Review and Meta-Analysis of the Comparative Data on Colposuspensions,Pubovaginal Slings,and Midurethral Tapes in the Surgical Treatment of Female Stress Urinary Incontinence

Context

Burch colposuspension, pubovaginal sling, and midurethral retropubic tape (RT) and transobturator tape (TOT) have been the most popular surgical treatments for female stress urinary incontinence (SUI). Several randomized controlled trials (RCTs) have been published comparing the different techniques, with conflicting results.

Objective

Our aim was to evaluate the efficacy, complication, and reoperation rates of midurethral tapes compared with other surgical treatments for female SUI.

Evidence acquisition

A systematic review of the literature was performed using the Medline, Embase, Scopus, Web of Science databases, and Cochrane Database of Systematic Reviews.

Evidence synthesis

Thirty-nine RCTs were identified. Patients receiving midurethral tapes had significantly higher overall (odds ratio [OR]: 0.61; confidence interval [CI]: 0.46–0.82; p = 0.00009) and objective (OR: 0.38; CI: 0.25–0.57; p < 0.0001) cure rates than those receiving Burch colposuspension, although they had a higher risk of bladder perforations (OR: 4.94; CI: 2.09–11.68; p = 0.00003). Patients undergoing midurethral tapes and pubovaginal slings had similar cure rates, although the latter were slightly more likely to experience storage lower urinary tract symptoms (LUTS) (OR: 0.31; CI: 0.10–0.94; p = 0.04) and had a higher reoperation rate (OR: 0.31; CI: 0.12–0.82; p = 0.02). Patients treated with RT had slightly higher objective cure rates (OR: 0.8;CI: 0.65–0.99; p = 0.04) than those treated with TOT; however, subjective cure rates were similar, and patients treated with TOT had a much lower risk of bladder and vaginal perforations (OR: 2.5; CI: 1.75–3.57; p < 0.00001), hematoma (OR: 2.62; CI: 1.35–5.08; p = 0.005), and storage LUTS (OR: 1.35; CI: 1.05–1.72; p = 0.02). Meta-analysis demonstrated similar outcomes for TVT-O (University of Liège, Liège, Wallonia, Belgium) and Monarc (AMS, Minnetonka, MN, USA).

Conclusions

Patients treated with RT experienced slightly higher continence rates than those treated with Burch colposuspension, but they faced a much higher risk of intraoperative complications. RT and pubovaginal slings were similarly effective, although patients with pubovaginal slings were more likely to experience storage LUTS. The use of RT was followed by objective cure rates slightly higher than TOT, but subjective cure rates were similar. TOT had a lower risk of bladder and vaginal perforations and storage LUTS than RT. The strength of these findings is limited by the heterogeneity of the outcome measures and the short length of follow-up.     

Complication Rates of Tension-Free Midurethral Slings in the Treatment of Female Stress Urinary Incontinence: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing Tension-Free Midurethral Tapes to Other Surgical Procedures and Different Devices

Objectives

To evaluate the complication rates of tension-free midurethral slings compared with other surgical treatments for stress urinary incontinence, including other tension-free midurethral slings.

Methods

A systematic review of the literature using MEDLINE, EMBASE, and Web of Science was performed in January 2007. Meta-analysis was conducted by using the Review Manager software 4.2.

Results

Our search identified 33 randomized controlled trials reporting data on complication rates. Our meta-analysis showed that complication rates were similar after tension-free vaginal tape (TVT) and Burch colposuspension, with the exclusion of bladder perforation, which was more common after TVT (p = 0.0001), and reoperation rate, which was significantly higher after Burch colposuspension (p = 0.02). TVT and pubovaginal sling were followed by similar complication rates. With regards to the comparisons among retropubic tapes, TVT and intravaginal slingplasty had similar complication rates, whereas suprapubic arc sling (SPARC) was complicated by higher rates of voiding lower urinary tract symptoms (LUTS) (p = 0.02) and reoperations (p = 0.04). Comparing retropubic and transobturator tapes, the occurrence of bladder perforations (p = 0.007), pelvic haematoma (p = 0.03), and storage LUTS (p = 0.01) was significantly less common in patients treated by transobturator tapes.

Conclusions

Tension-free slings were followed by lower risk of reoperation compared with Burch colposuspension, whereas pubovaginal sling and tension-free midurethral slings had similar complication rates. With regards to different tension-free tapes, voiding LUTS and reoperations were more common after SPARC, whereas bladder perforations, pelvic haematoma, and storage LUTS were less common after transobturator tapes. The quality of many evaluated studies was limited.     

Solifenacin Plus Tamsulosin Combination Treatment in Men With Lower Urinary Tract Symptoms and Bladder Outlet Obstruction: A Randomized Controlled Trial

Background

Alpha blockers are prescribed to manage lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Antimuscarinics are prescribed to treat overactive bladder (OAB).

Objective

To investigate the safety of a combination of solifenacin (SOLI) and tamsulosin oral controlled absorption system (TOCAS) in men with LUTS and bladder outlet obstruction (BOO).

Design, setting, and participants

Randomized, double-blind, parallel-group, placebo-controlled study in men aged >45 yr with LUTS and BOO for ≥3 mo, total International Prostate Symptom Score (IPSS) ≥8, BOO index ≥20, maximum urinary flow rate (Q_max) ≤12 ml/s, and voided volume ≥120 ml.

Interventions

Once-daily coadministration of TOCAS 0.4 mg plus SOLI 6 mg, TOCAS 0.4 mg plus SOLI 9 mg, or placebo for 12 wk.

Outcome measurements and statistical analysis

Primary (safety) measurements: Q_max and detrusor pressure at Q_max (P_detQ_max). Other safety assessments included postvoid residual (PVR) volume. Secondary end points included bladder contractile index (BCI) score and percent bladder voiding efficiency (BVE). An analysis of covariance model compared each TOCAS plus SOLI combination with placebo.

Results and limitations

Both active treatment groups were noninferior to placebo at end of treatment (EOT) for P_detQ_max and Q_max. Mean change from baseline PVR was significantly higher at all time points for TOCAS 0.4 mg plus SOLI 6 mg, and at weeks 2, 12, and EOT for TOCAS 0.4 mg plus SOLI 9 mg versus placebo. Both treatment groups were similar to placebo for BCI and BVE. Urinary retention was seen in only one patient receiving TOCAS 0.4 mg plus SOLI 6 mg. Limitations of the study were that prostate size and prostate-specific antigen level were not measured.

Conclusions

TOCAS 0.4 mg plus SOLI 6 mg or 9 mg was noninferior to placebo at EOT for P_detQ_max and Q_max in men with LUTS and BOO, and there was no clinical or statistical evidence of increased risk of urinary retention.     

Influence of Preoperative and Postoperative Pelvic Floor Muscle Training (PFMT) Compared with Postoperative PFMT on Urinary Incontinence After Radical Prostatectomy: A Randomized Controlled Trial

Background

The efficacy of preoperative pelvic floor muscle training (PFMT) for urinary incontinence (UI) after open radical prostatectomy (ORP) and robot-assisted laparoscopic radical prostatectomy (RARP) is still unclear.

Objective

To determine whether patients with additional preoperative PFMT regain urinary continence earlier than patients with only postoperative PFMT after ORP and RARP.

Design, setting, and participants

A randomized controlled trial enrolled 180 men who planned to undergo ORP/RARP.

Intervention

The experimental group (E, n = 91) started PFMT 3 wk before surgery and continued after surgery. The control group (C, n = 89) started PFMT after catheter removal.

Outcome measurements and statistical analysis

The primary end point was time to continence. Patients measured urine loss daily (24-h pad test) until total continence (three consecutive days of 0 g of urine loss) was achieved. Secondary end points were 1-h pad test, visual analog scale (VAS), International Prostate Symptom Score (IPSS), and quality of life (King's Health Questionnaire [KHQ]). Kaplan-Meier analysis and Cox regression with correction for two strata (age and type of surgery) compared time and continence. The Fisher exact test was applied for the 1-h pad test and VAS; the Mann-Whitney U test was applied for IPSS and KHQ.

Results and limitations

Patients with additional preoperative PFMT had no shorter duration of postoperative UI compared with patients with only postoperative PFMT (p = 0.878). Median time to continence was 30 and 31 d, and median amount of first-day incontinence was 108 g and 124 g for groups E and C, respectively. Cox regression did not indicate a significant difference between groups E and C (p = 0.773; hazard ratio: 1.047 [0.768–1.425]). The 1-h pad test, VAS, and IPSS were comparable between both groups. However, “incontinence impact” (KHQ) was in favor of group E at 3 mo and 6 mo after surgery.

Conclusions

Three preoperative sessions of PFMT did not improve postoperative duration of incontinence.

Trial registration

Netherlands Trial Register No. NTR 1953.     

Pure Natural Orifice Translumenal Endoscopic Surgery (NOTES) Transvaginal Nephrectomy

Natural orifice translumenal endoscopic surgery (NOTES) within urology has largely been limited to experimental animal studies and diagnostic procedures in humans. Attempts to complete a pure NOTES transvaginal nephrectomy have thus far been unsuccessful. We report the first clinical experience with pure NOTES transvaginal nephrectomy.     

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.     

Comprehensive Standardized Report of Complications of Retropubic and Laparoscopic Radical Prostatectomy

Background

The lack of standardized reporting of the complications of radical prostatectomy in the literature has made it difficult to compare incidences across institutions and across different surgical approaches.

Objective

To define comprehensively the incidence, severity, and timing of onset of medical and surgical complications of open retropubic prostatectomy (RP) and laparoscopic radical prostatectomy (LP) using a standardized reporting methodology to facilitate comparison.

Design, setting, and participants

Between January 1999 and June 2007, 4592 consecutive patients underwent RP or LP without prior radiation or hormonal therapy. Median follow-up was 36.9 mo (interquartile range: 20.3–60.6).

Intervention

Open or laparoscopic radical prostatectomy.

Measurements

All medical and surgical complications of radical prostatectomy were captured and graded according to the modified Clavien classification and classified by timing of onset.

Results and limitations

There were 612 medical complications in 467 patients (10.2%) and 1426 surgical complications in 925 patients (20.1%). The overall incidences of early minor and major medical and surgical complications for RP were 8.5% and 1.5% for medical and 11.4% and 4.9% for surgical complications, respectively. The overall incidences of early minor and major medical and surgical complications for LP were 14.2% and 2.3% for medical and 23.1% and 6.6% for surgical complications, respectively. On multivariate analysis, LP approach was associated with a higher incidence of any grade medical and surgical complications but a lower incidence of major surgical complications than RP. Six hundred fifty-two men (14.2%) visited the emergency department, and 240 men (5.2%) required readmission. The main limitation is the retrospective nature.

Conclusions

With standardized reporting, the incidence of some complications is higher than recognized in the literature. Although most complications are minor in severity, medical and surgical complications are observed in approximately 10% and 20% of patients, respectively. Accurate reporting of complications through a standardized methodology is essential for counseling patients regarding risk of complications, for identifying modifiable risk factors, and for facilitating comparison across institutions and approaches.     

Predicting Occult Multifocality of Renal Cell Carcinoma

Background

Multifocal renal cell carcinoma (RCC) has been reported in up to 25% of all radical nephrectomy specimens. Modern imaging tends to underestimate the rate of multifocality. Recognition of multifocality before treatment may guide physicians and patients to the type of intervention and tailor long-term follow-up.

Objective

Our aim was to develop and assess preoperative nomograms to predict occult multifocal RCC.

Design, setting, and participants

We evaluated 560 consecutive patients undergoing radical nephrectomy for clinically localized suspected sporadic RCC between 2000 and 2008 in a tertiary center. Clinically manifest multifocal lesions were excluded. Logistic regression models were used to assess the potential risk factors of occult multifocality with and without pathologic variables that may be available with preoperative biopsy. Nomograms were developed and assessed for diagnostic properties.

Interventions

All patients underwent radical nephrectomy.

Measurements

Assessments of risk factors for occult multifocal RCC were obtained using regression models and nomograms.

Results and limitations

The incidence of occult multifocality was 7.9%. Significantly associated predictors of multifocality were male gender, family history of malignancy other than RCC, radiographic size of the lesion, histologic subtype other than clear cell, and Fuhrman grade IV. The two designed nomograms had 0.75 and 0.82 concordance indices, respectively.

Conclusions

Our data suggest that occult multifocal RCC is more frequently associated with small (2–4 cm) renal lesions. Male gender, family history of kidney cancer, histologic subtype, and grade are strongly associated with an increased risk of occult multifocal RCC. The developed nomograms had good predictive accuracy that was enhanced when combined with pathologic variables.     

Comparative results of two techniques to treat stress urinary incontinence: synthetic transobturator and aponeurotic slings

Introduction and hypothesis  This study aims to analyze comparatively the efficacy and safety of synthetic transobturatory and aponeurotic retropubic slings, in the treatment of stress urinary incontinence (SUI) in women. Methods  Patients were separated in a randomized way. Twenty-one patients were submitted to the operatory correction by the transobturatory sling technique, whereas 20 patients were operated by the retropubic sling technique. All patients were submitted to complete physical exam and urodynamic test. The “T” test and the Mann–Whitney U test were applied to establish comparisons between the two groups. Patients were followed-up for 12 months. Results  Healing rate was 90.5% (19/21) and 95% (19/20), respectively after 12 months. The transobturatory group presented lesser complications rate than the retropubic group. Conclusions  The transobturatory and the aponeurotic slings techniques were equally effective for the treatment of SUI. The transobturatory sling has shown fewer complications and lesser surgical time than the aponeurotic sling technique.     

Systematic Review and Meta-analysis of Candidate Gene Association Studies of Lower Urinary Tract Symptoms in Men

Context

Although family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS.

Objective

To systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations.

Evidence acquisition

A systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies.

Evidence synthesis

We identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49–0.83) with moderate heterogeneity (I² = 27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes.

Conclusions

Few putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses.

Patient summary

Combining the results from all previous studies of genetic variants that may cause urinary symptoms in men, we found significant variants in five genes. Only one, a variant of the vitamin D receptor, was consistently protective across different populations.     

Retroperitoneal Laparoendoscopic Single-Site Surgery: Preliminary Experience in Kidney and Ureteral Indications

The advantages of retroperitoneoscopic technique are well known. We decided to combine this access with the emerging laparoendoscopic single-site surgery (LESS) technique. We present our preliminary data on 11 renoureteral procedures and describe our retroperitoneoscopic LESS technique.     

Incidence of Prostate Cancer After Termination of Screening in a Population-based Randomised Screening Trial

Background

In a previous publication from the Göteborg randomised screening trial from 2010, biennial prostate-specific antigen (PSA) screening for men ≤69 yr of age was shown to lower prostate cancer (PCa) mortality by 44%. The evidence of the optimal age to stop screening, however, is limited.

Objective

To examine the risk of PCa after the discontinuation of screening.

Design, setting, and participants

In December 1994, 20 000 men in Göteborg, Sweden, between the ages of 50 and 65 yr were randomised to a screening arm (invited biennially to PSA testing) and a control arm (not invited). At the upper age limit (average: 69 yr), a total of 13 423 men (6449 and 6974 in the screening and control arms, respectively) were still alive without PCa. The incidence of PCa hereafter was established by matching with the Western Swedish Cancer Register. Participants were followed until a diagnosis of PCa, death, or final follow-up on June 30, 2012, or for a maximum of 12 yr after the last invitation.

Outcome measurements and statistical analysis

Incidence rates and disease-free survival were calculated with life table models and Kaplan-Meier estimates. A competing risk model was also applied.

Results and limitations

Postscreening, 173 cases of PCa were diagnosed in the screening arm (median follow-up: 4.8 yr) and 371 in the control arm (median follow-up: 4.9 yr). Up to 9 yr postscreening, all risk groups were more commonly diagnosed in the control arm, but after 9 yr the rates in the screening arm caught up, other than those for the low-risk group. PCa mortality also caught up after 9 yr.

Conclusions

Nine years after the termination of PSA testing, the incidence of potentially lethal cancers equals that of nonscreened men. Considering the high PCa mortality rate in men >80 yr of age, a general age of 70 yr to discontinue screening might be too low. Instead, a flexible age to discontinue based on individual risk stratification should be recommended.     

Assessing the Impact of Ischaemia Time During Partial Nephrectomy

Context

The impact of applying renal ischaemia during nephron-sparing surgery to avoid renal damage in the treated kidney has gained importance in different surgical techniques.

Objective

The main objective of the present study is to point out the limit of renal ischaemia times for warm and cold ischaemia approaches. Important results of research on renal ischaemia and different surgical techniques as well as results of clinical studies concerning renal function after renal ischaemia in partial nephrectomy are highlighted.

Evidence acquisition

A Medline literature research was performed, combining queries on the keywords nephron-sparing surgery, partial nephrectomy, and ischemia. Links to related articles and cross-reading of citations in related articles were surveyed, as were reviews, letters to editors, and information collected from urologic textbooks. The references formed the basis of this review article, with selection and deletion based on the relevance and importance of the content. In a final step, interactive peer review by the expert panel of coauthors completed the review.

Evidence synthesis

Renal ischaemia research showed an increasing renal damage proportional to ischemic time. Current clinical data support safe ischaemia times, within 20 min of warm ischaemia and up to 2 h of cold ischaemia, to minimise renal ischemic damage. To date, no ischaemia dose-response curve or algorithm is available to predict the risk of acute kidney injury and chronic kidney disease in patients undergoing intraoperative ischaemia. In general, there seems to be a higher risk for comorbidity caused by renal damage in patients suffering from kidney tumour.

Conclusions

If ischaemia is required, the tumour should be removed within 20 min of warm ischaemia, regardless of surgical approach. Efforts should be made to start immediately with cold ischaemia, if the feasibility within this span of time seems to be jeopardised. Thus, cold ischaemia times up to 2 h can be tolerated by the kidney, depending on the individual method. Nevertheless, cold ischaemia with ice slush should be kept as short as possible—at best within 35 min. In ischemic nephron-sparing surgery, one of the surgeon's main aims should be to avoid loss of renal function. Only after optimal preoperative appraisal and planning can the best postoperative outcomes for renal function be achieved.     

Thirty-Day Mortality After Nephrectomy: Clinical Implications for Informed Consent

Background

The existing literature suggests that the surgical mortality (SM) observed with nephrectomy for localised disease varies from 0.6% to 3.6%.

Objective

To examine age- and stage-specific 30-d mortality (TDM) rates after partial or radical nephrectomy.

Design, setting, and participants

We relied on 24 535 assessable patients from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database.

Measurements

In 12 283 patients, logistic regression models were used to develop a tool for pretreatment prediction of the probability of TDM according to individual patient and tumour characteristics. External validation was performed on 12 252 patients.

Results and limitations

In the entire cohort of 24 535 patients, 219 deaths occurred during the initial 30 d after nephrectomy (0.9% TDM rate). TDM increased with age (≤49 yr: 0.5% vs 50–59 yr: 0.7% vs 60–69 yr: 0.9% vs 70–79 yr: 1.2% vs ≥80 yr: 2.0%; χ² trend p < 0.001) and stage (0.3% for T1–2N0M0 vs 1.3% for T3–4N0–2M0 vs 4.2% for T1–4N0–2M1; χ² trend p = <0.001). TDM decreased in more recent years (1988–1993: 1.3% vs 1994–1998: 0.9% vs 1999–2002: 0.7% vs 2003–2004: 0.6%; χ² trend p < 0.001) and was lower after partial versus radical nephrectomy (RN) (0.4% vs 0.9%; p = 0.008). Only age (p < 0.001) and stage (p < 0.001) achieved independent predictor status. The look-up table that relied on the regression coefficients of age and stage reached 79.4% accuracy in the external validation cohort.

Conclusions

Age and stage are the foremost determinants of TDM after nephrectomy. Our model provides individual probabilities of TDM after nephrectomy, and its use should be highly encouraged during informed consent prior to planned nephrectomy.     

Obesity and Prostate Cancer: Weighing the Evidence

Context

Obesity and prostate cancer (PCa) affect substantial proportions of Western society. Mounting evidence, both epidemiologic and mechanistic, for an association between the two is of public health interest. An improved understanding of the role of this modifiable risk factor in PCa etiology is imperative to optimize screening, treatment, and prevention.

Objective

To consolidate and evaluate the evidence for an epidemiologic link between obesity and PCa, in addition to examining the proposed underlying molecular mechanisms.

Evidence acquisition

A PubMed search for relevant articles published between 1991 and July 2012 was performed by combining the following terms: obesity, BMI, body mass index and prostate cancer risk, prostate cancer incidence, prostate cancer mortality, radical prostatectomy, androgen-deprivation therapy, external-beam radiation, brachytherapy, prostate cancer and quality of life, prostate cancer and active surveillance, in addition to obesity, BMI, body mass index and prostate cancer and insulin, insulin-like growth factor, androgen, estradiol, leptin, adiponectin, and IL-6. Articles were selected based on content, date of publication, and relevancy, and their references were also searched for relevant articles.

Evidence synthesis

Increasing evidence suggests obesity is associated with elevated incidence of aggressive PCa, increased risk of biochemical failure following radical prostatectomy and external-beam radiotherapy, higher frequency of complications following androgen-deprivation therapy, and increased PCa-specific mortality, although perhaps a lower overall PCa incidence. These results may in part relate to difficulties in detecting and treating obese men. However, multiple molecular mechanisms could explain these associations as well. Weight loss slows PCa in animal models but has yet to be fully tested in human trials.

Conclusions

Obesity appears to be linked with aggressive PCa. We suggest clinical tips to better diagnose and treat obese men with PCa. Whether reversing obesity slows PCa growth is currently unknown, although it is an active area of research.     

Testosterone and Prostate Cancer: Revisiting Old Paradigms

Context

Androgens are vital for growth and maintenance of the prostate; however, the notion that pathologic prostate growth, benign or malignant, can be stimulated by androgens is a commonly held belief without scientific basis. Therefore, the current prostatic guidelines for testosterone therapy (TT) appear to be overly restrictive and should be reexamined.

Objective

To review the literature addressing the possible relationship between testosterone and prostate cancer (PCa) and to summarize the main aspects of this issue.

Evidence acquisition

A Medline search was conducted to identify original articles, review articles, and editorials addressing the relationship between testosterone and the risk of PCa development, as well as the impact of TT on PCa development and its natural history in men believed to be cured by surgery or radiation.

Evidence synthesis

Serum androgen levels, within a broad range, are not associated with PCa risk. Conversely, at time of PCa diagnosis, low rather than high serum testosterone levels have been found to be associated with advanced or high-grade disease. The available evidence indicates that TT neither increases the risk of PCa diagnosis nor affects the natural history of PCa in men who have undergone definitive treatment without residual disease. These findings can be explained with the saturation model (which states that prostatic homeostasis is maintained by a relatively low level of androgenic stimulation) and with the observation that exogenous testosterone administration does not significantly increase intraprostatic androgen levels in hypogonadal men. It must, however, be recognized that the literature remains limited regarding the effect of TT on PCa risk. Nonetheless, the current European Association of Urology guidelines state that in hypogonadal men who were successfully treated for PCa, TT can be considered after a prudent interval.

Conclusions

Although no controlled studies have yet been performed and there is a paucity of long-term data, the available literature strongly suggests that TT neither increases the risk of PCa diagnosis in normal men nor causes cancer recurrence in men who were successfully treated for PCa. Large prospective studies addressing the long-term effect of TT are needed to either refute or corroborate these hypotheses.     

Metabolism of Kidney Cancer: From the Lab to Clinical Practice

Context

There is increasing evidence for the role of altered metabolism in the pathogenesis of renal cancer.

Objective

This review characterizes the metabolic effects of genes and signaling pathways commonly implicated in renal cancer.

Evidence acquisition

A systematic review of the literature was performed using PubMed. The search strategy included the following terms: renal cancer, metabolism, HIF, VHL.

Evidence synthesis

Significant progress has been made in the understanding of the metabolic derangements present in renal cancer. These findings have been derived through translational, in vitro, and in vivo studies. To date, the most well-characterized metabolic features of renal cancer are linked to von Hippel-Lindau (VHL) loss. VHL loss and the ensuing increase in the expression of hypoxia-inducible factor affect several metabolic pathways, including glycolysis and oxidative phosphorylation. Collectively, these changes promote a glycolytic metabolic phenotype in renal cancer. In addition, other histologic subtypes of renal cancer are also notable for metabolic derangements that are directly related to the causative genes.

Conclusions

Current knowledge of the genetics of renal cancer has led to significant understanding of the metabolism of this malignancy. Further studies of the metabolic basis of renal cell carcinoma should provide the foundation for the development of new treatment approaches and development of novel biomarkers.