Tag Archive for: Article of the Month

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Video: IFES to manage non-neuropathic UAB in children

Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial

Abdol-Mohammad Kajbafzadeh, Lida Shari-Rad*, Seyedeh-Sanam Ladi-Seyedian and Sarah Mozafarpour

 

Department of Pediatric Urology, Pediatric Urology Research Center, and *Department of Physical Therapy, ChildrenHospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

 

Objectives

To assess the efficacy of transcutaneous interferential electrical stimulation (IFES) and urotherapy in the management of non-neuropathic underactive bladder (UAB) in children with voiding dysfunction.

Patients and Methods

In all, 36 children with UAB without neuropathic disease [15 boys, 21 girls; mean (sd) age 8.9 (2.6) years] were enrolled and then randomly allocated to two equal treatment groups comprising IFES and control groups. The control group underwent only standard urotherapy comprising diet, hydration, scheduled voiding, toilet training, and pelvic floor and abdominal muscles relaxation. Children in the IFES group likewise underwent standard urotherapy and also received IFES. Children in both groups underwent a 15-session treatment programme twice a week. A complete voiding and bowel habit diary was completed by parents before, after treatment, and 1 year later. Bladder ultrasound and uroflowmetry/electromyography were performed before, at the end of treatment course, and at the 1-year follow-up.

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Results

The mean (sd) number of voiding episodes before treatment was 2.6 (1) and 2.7 (0.76) times/day in the IFES and control groups, respectively, which significantly increased after IFES therapy in IFES group, compared with only standard urotherapy in the control group [6.3 (1.4) vs 4.7 (1.3) times/day, P < 0.002). The mean (sd) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively, which decreased significantly at 1 year after treatment in the IFES group compared with the controls, at 227 (86) vs 344 (127) mL (P < 0.01). Maximum urine flow increased and voiding time decreased significantly in the IFES group compared with controls at the end of treatment sessions and 1 year later (P < 0.05). All the children had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of 18 (33%) in the control group by the end of follow-up (P < 0.007). At the end of the treatment course, night-time wetting was improved in all children who had this symptom before the treatment in the IFES group (P < 0.01).

Conclusion

Combining IFES and urotherapy is a safe and effective therapy in the management of children with UAB.

Article of the Month: Enclomiphene for Secondary Hypogonadism – Restoration not Replacement

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

The second post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Andrew McCullough, discussing his paper.

If you only have time to read one article this week, it should be this one.

Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement

Edward D. Kim, Andrew McCullough* and Jed Kaminetsky

 

University of Tennessee Graduate School of Medicine, Knoxville, TN
*Urological Institute of Northeastern, New York, NY, USA, and University Urology Associates, New York, NY, USA

 

 

Enclomiphene-infographic_sm

Click on image for full size infographic

Objectives

To determine the effects of daily oral doses of enclomiphene citrate compared with topical testosterone gel treatment on serum total testosterone (TT), luteinising hormone (LH), follicle-stimulating hormone (FSH), and sperm counts in men with secondary hypogonadism.

Patients and Methods

  • selective oestrogen receptor modulator

Two parallel randomised, double-blind, double-dummy, placebo-controlled, multicentre, phase III studies were undertaken to evaluate two doses of enclomiphene citrate vs testosterone gel (AndroGel®1.62%) on TT, LH, FSH, and sperm counts in overweight men aged 18–60 years with secondary hypogonadism. Men were screened and enrolled in the trials (ZA-304 and ZA-305). All enrolled men had early morning serum TT levels in the low or low normal range (≤300 ng/dL; ≤10.4 nmol/L) and had low or normal LH (<9.4 IU/L) levels measured on two separate occasions 2–10 days apart. Serum samples were obtained over the course of the study to determine relevant hormone levels at baseline and after 16 weeks of treatment. Men provided semen samples twice to enroll at the beginning and twice at the end of the study.

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Results

TT levels increased between baseline and after 16 weeks of treatment in all the treatment groups. FSH and LH levels increased in the enclomiphene citrate groups and decreased in the testosterone gel group at 16 weeks. Enclomiphene citrate maintained sperm concentration in the normal range over the treatment period, while there was a marked reduction in spermatogenesis in the testosterone gel group.

Conclusions

Enclomiphene citrate consistently increased serum TT, LH and FSH, restoring normal levels of serum TT. Enclomiphene citrate treatment maintained sperm concentrations in the normal range. The effects on TT were also seen with testosterone replacement via testosterone gel but sperm counts were not maintained.

Video: Restoration not Replacement – Enclomiphene for Secondary Hypogonadism

Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement

Edward D. Kim, Andrew McCullough* and Jed Kaminetsky

 

University of Tennessee Graduate School of Medicine, Knoxville, TN
*Urological Institute of Northeastern, New York, NY, USA, and University Urology Associates, New York, NY, USA

 

Objectives

To determine the effects of daily oral doses of enclomiphene citrate compared with topical testosterone gel treatment on serum total testosterone (TT), luteinising hormone (LH), follicle-stimulating hormone (FSH), and sperm counts in men with secondary hypogonadism.

Patients and Methods

Two parallel randomised, double-blind, double-dummy, placebo-controlled, multicentre, phase III studies were undertaken to evaluate two doses of enclomiphene citrate vs testosterone gel (AndroGel®1.62%) on TT, LH, FSH, and sperm counts in overweight men aged 18–60 years with secondary hypogonadism. Men were screened and enrolled in the trials (ZA-304 and ZA-305). All enrolled men had early morning serum TT levels in the low or low normal range (≤300 ng/dL; ≤10.4 nmol/L) and had low or normal LH (<9.4 IU/L) levels measured on two separate occasions 2–10 days apart. Serum samples were obtained over the course of the study to determine relevant hormone levels at baseline and after 16 weeks of treatment. Men provided semen samples twice to enroll at the beginning and twice at the end of the study.

AprAOTM

Results

TT levels increased between baseline and after 16 weeks of treatment in all the treatment groups. FSH and LH levels increased in the enclomiphene citrate groups and decreased in the testosterone gel group at 16 weeks. Enclomiphene citrate maintained sperm concentration in the normal range over the treatment period, while there was a marked reduction in spermatogenesis in the testosterone gel group.

Conclusions

Enclomiphene citrate consistently increased serum TT, LH and FSH, restoring normal levels of serum TT. Enclomiphene citrate treatment maintained sperm concentrations in the normal range. The effects on TT were also seen with testosterone replacement via testosterone gel but sperm counts were not maintained.

Article of the Month: ERSPC and PCPT risk calculators in prostate cancer risk prediction

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary European cohort

Cedric Poyet, Daan Nieboer*, Bimal Bhindi, Girish S. Kulkarni, Caroline WiederkehrMarian S. Wettstein, Remo Largo, Peter Wild, Tullio Sulser and Thomas Hermanns 

 

Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, *Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands, Division of Urology, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada, and Institute of Surgical Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

 

Objectives

To externally validate and compare the two novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC)-prostate cancer risk calculator (RC) and Prostate Cancer Prevention Trial (PCPT)-RC.

Patients and Methods

All men who underwent a transrectal prostate biopsy in a European tertiary care centre between 2004 and 2012 were retrospectively identified. The probability of detecting prostate cancer and significant cancer (Gleason score ≥7) was calculated for each man using the novel versions of the ERSPC-RC (DRE-based version 3/4) and the PCPT-RC (version 2.0) and compared with biopsy results. Calibration and discrimination were assessed using the calibration slope method and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, decision curve analyses were performed.

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Results

Of 1 996 men, 483 (24%) were diagnosed with prostate cancer and 226 (11%) with significant prostate cancer. Calibration of the two RCs was comparable, although the PCPT-RC was slightly superior in the higher risk prediction range for any and significant prostate cancer. Discrimination of the ERSPC- and PCPT-RC was comparable for any prostate cancer (AUCs 0.65 vs 0.66), while the ERSPC-RC was somewhat better for significant prostate cancer (AUCs 0.73 vs 0.70). Decision curve analyses revealed a comparable net benefit for any prostate cancer and a slightly greater net benefit for significant prostate cancer using the ERSPC-RC.

Conclusions

In our independent external validation, both updated RCs showed less optimistic performance compared with their original reports, particularly for the prediction of any prostate cancer. Risk prediction of significant prostate cancer, which is important to avoid unnecessary biopsies and reduce over-diagnosis and overtreatment, was better for both RCs and slightly superior using the ERSPC-RC.

Editorial: Prostate cancer risk prediction and the persistence of uncertainty

Poyet et al. [1] have performed the largest external validation of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) v2.0 risk calculators (RCs) to date, having retrospectively identified 1996 men undergoing prostate biopsy in a Swiss tertiary care facility.

Asides from the validatory nature of this paper [1], there are several other findings though less novel, which are further important additions to the urological literature.

This study confirms the superior discriminative performance of multi-factorial RCs over PSA alone in the assessment of prostate cancer: where the area under the receiver operating characteristic curve (AUC) for the prediction of significant prostate cancer for PSA alone was 0.65, comparing less favourably than 0.73 and 0.70 for the ERSPC and PCPT v2.0 RCs, respectively.

The authors performed sensitivity analysis showing higher detection rates for prostate cancer (29.4% vs 18.1%) and significant prostate cancer (15.9% vs 5.9%) in patients receiving a 12-core biopsy than in those receiving a 6–8 core biopsy.

Supplementary analysis by the authors evaluated the performance of previous versions of the PCPT-RC, specifically v1.0 and PCPT-RC v1.0 with prostate volume. The inclusion of prostate volume demonstrated an improved predictive ability of this RC. The AUC for the prediction of significant prostate cancer using the PCPT-RC v1.0 with prostate volume was 0.74. This contrasts with the ERSPC risk tool: AUC of 0.73 (which includes a trichotomised estimation of prostate volume), and the novel PCPT-RC v2.0; AUC of 0.70 (which does not include prostate volume as a factor).

The authors conclude that the prediction of significant prostate cancer was superior using the ERSPC-RC compared with the PCPT-RC v2.0, in risk thresholds of 8–35%. Their data also shows that the PCPT-RC v2.0 offers a superior net benefit to the ERPSC-RC to a large number of men outside of this range of threshold probabilities. Their findings suggest that the older PCPT-RC v1.0 with prostate volume may offer benefits superior to both the ERSPC and PCPT v2.0 RCs.

The authors assessment of novel risk tools confirms the rationale for guidelines and consensus statements that PSA testing should not be considered on its own, but rather as part of a multivariate approach [2, 3]. This current work suggests that although calibration of risk tools is still not optimal, they offer superior discriminative ability and superior net benefit in identifying patients with significant prostate cancer. This work affirms the role for variables such as DRE, and the importance of prostate volume in addition to PSA in prostate cancer assessment.

Although further refinement of risk tools is necessary, this work encourages confidence in and should garner further traction for the routine use of such tools in the assessment and counselling of patients before prostate biopsy.

Dara J. Lundon*
*Conway Institute of Biomedical and Biomolecular Science, University College Dublin School of Medicine and Medical Sciences, University College Dublin, Beleld, and Department of Urology, Mater Misericordiae University Hospital, Dublin, Ireland

 

References

 

 

Article of the Month: SRP for recurrent Prostate Cancer – Verification of EAU guideline criteria

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Salvage Radical Prostatectomy for recurrent Prostate Cancer: Verification of EAU guideline criteria

Philipp Mandel*, Thomas Steuber*, Sascha Ahyai, Maximilian Kriegmair, Jonas Schiffmann*, Katharina Boehm*, Hans Heinzer*, Uwe Michl*, Thorsten Schlomm*†, Alexander Haese*, Hartwig Huland*, Markus Graefen* and Derya Tilki*

 

*Martini-Clinic Prostate Cancer Center, Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg and ‡Department of Urology, University Hospital Mannheim, Mannheim, Germany

 

Note: Figure 3 should be swapped with Figure 4. The legends for both figures stay the same and the referencing in the text is correct.

OBJECTIVE

To analyse oncological and functional outcomes of salvage radical prostatectomy (SRP) in patients with recurrent prostate cancer and to compare outcomes of patients within and outside the European Association of Urology (EAU) guideline criteria (organ-confined prostate cancer ≤T2b, Gleason score ≤7 and preoperative PSA level <10 ng/mL) for SRP.

PATIENTS AND METHODS

In all, 55 patients who underwent SRP from January 2007 to December 2012 were retrospectively analysed. Kaplan–Meier curves assessed time to biochemical recurrence (BCR), metastasis-free survival (MFS) and cancer-specific survival. Cox regressions addressed factors influencing BCR and MFS. BCR was defined as a PSA level of >0.2 ng/mL and rising, continence as the use of 0–1 safety pad/day, and potency as a five-item version of the International Index of Erectile Function score of ≥18.

RESULTS

The median follow-up was 36 months. After SRP, 42.0% of the patients experienced BCR, 15.9% developed metastasis, and 5.5% died from prostate cancer. Patients fulfilling the EAU guideline criteria were less likely to have positive lymph nodes (LNs) and had significantly better BCR-free survival (5-year BCR-free survival 73.9% vs 11.6%; P = 0.001). In multivariate analysis, low-dose-rate brachytherapy as primary treatment (P = 0.03) and presence of positive LNs at SRP (P = 0.02) were significantly associated with worse BCR-free survival. The presence of positive LNs or Gleason score >7 at SRP were independently associated with metastasis. The urinary continence rate at 1 year after SRP was 74%. Seven patients (12.7%) had complications ≥III (Clavien grade).

CONCLUSION

SRP is a safe procedure providing good cancer control and reasonable urinary continence. Oncological outcomes are significantly better in patients who met the EAU guideline recommendations.

Editorial: SRP – a few good men

The current management of recurrent disease after definitive treatment of a localized prostate cancer with radiation therapy (RT) or cryotherapy remains debatable. A substantial portion of patients treated with RT (20–50%) will experience biochemical recurrence. Androgen deprivation therapy has been the mainstay of therapy for this patient population, especially if there was concern about metastatic spread. As the initial experience with salvage radical prostatectomy (SRP) was highly morbid with poor functional outcomes, this did not gain strong acceptance as a recommended treatment method; however, with improved functional outcomes and fewer complications reported in recent series, SRP has once again become a viable alternative in select cases.

The rarity of the procedure makes it difficult to generate large-volume prospective studies on SRP, requiring us to depend on retrospective series. Chade et al. [1] published the largest series of patients undergoing SRP through a multicentre collaborative effort, and were able to identify 404 patients treated between 1985 and 2009; other large series were limited to 50–200 patients. In their systematic review of studies published between 1980 and 2011, Chade et al. [2] reported 5- and 10-year biochemical recurrence-free survival rates of 47–82% and 28–53%, respectively. This broad range of outcomes hints at the variable response of patients to SRP. Identifying the subset of patients who are most likely to benefit from SRP will therefore help tailor therapies for patients who have failed RT, cryotherapy or high-intensity focused ultrasonography.

As described by Mandel et al. [3], there are three sets of guidelines currently addressing patient selection for SRP. The NICE guidelines are the least specific, essentially mentioning SRP as an option for management without specifying specific criteria [4]. The European Association of Urology (EAU) and National Comprehensive Cancer Network guidelines are more specific, and help narrow the patient population to men with clinically localized recurrence (cT1–2), life expectancy of at least 10 years and a preoperative PSA level <10 ng/mL[5, 6]. The EAU guidelines are even more restrictive, limiting selection to men with Gleason ≤7 on prostate biopsy, although they do not specify whether that is before or after RT [5].

In their retrospective analysis of 55 patients treated with SRP between 2007 and 2012, Mandel et al. [3] compare the oncological outcomes of patients treated according to the EAU criteria (n = 32) and those treated without meeting the EAU criteria (n = 23). The 5-year biochemical recurrence-free survival rate was 48.7%, consistent with previous studies, as was the 5-year cancer-specific survival rate of 89%. Importantly, however, after stratification based on EAU criteria, the 5-year biochemical recurrence-free survival rates were drastically different: 73.9% in patients who met the EAU criteria and 11.6% in patients who did not. Patients who did not meet the EAU criteria were more likely to have Gleason score ≥8 (P = 0.08) tumours and pN1 (nodal metastatic) disease at the time of SRP (P = 0.04), which shows the ability of these criteria to select patients with localized disease recurrence. They also established that overall functional outcomes were acceptable after this procedure, with a postoperative urinary continence rate of 74%; none of the patients recovered potency, however, which is not surprising considering the high rate of preoperative erectile dysfunction and the non-nerve-sparing nature of the procedure [3].

In terms of complications, 12.7% of the patients had Clavien ≥ III complications requiring additional intervention. When complications do occur, they can be severe: three of the patients (5.5%) developed rectovesical fistulae and failed conservative management, progressing to fistula repair with omental flap, and two of the patients required permanent urinary diversion. There was no specification, however, regarding which subset of patients experienced these complications. The complication rate was acceptable, and consistent with recent reports of decreased complication rates with SRP [3].

While the study has its limitations as a retrospective review of a relatively small cohort, it is the first to analyse outcomes based on published guidelines criteria, and thereby helps to validate the subset of patients that will benefit from surgical intervention. Based on their findings, appropriately selected patients, those with evidence of truly localized recurrent disease after RT or high-intensity focused ultrasonography, can have significant oncological benefit with acceptable functional outcomes and without significant morbidity. The goal is not to perform SRP indiscriminately, rather to wait for a few good men.

Thenappan Chandrasekar , and Christopher P. Evans
Department of Urology, University of California, Sacramento, CA, USA

 

References

 

1 Chade DC, Shariat SF, Cronin AM et al. Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration. Eur Urol 2011; 60: 20510

 

2 Chade DC, Eastham J, Graefen M et al. Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. Eur Urol 2012; 61: 96171

 

3 MandelP, Steuber T, Ahyai S et al. Salvage radical prostatectomy for recurrent prostate cancer: verication of European Association of Urology guideline criteria. BJU Int 2015; 117: 5561

 

4 Prostate cancer: diagnosis and treatment. NICE clinical guideline 175: Hearing before the National Institute for Health and Care Excellence (January 2014).

 

5 Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65: 46779

 

6 Mohler JL, Kantoff PW, Armstrong AJ et al. Prostate cancer, version 2.2014. JNCCN 2014; 12: 686718.

 

 

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