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Editorial: Choline-PET/CT in relapsing prostate cancer patients

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18F-choline positron emission tomography (PET)/C T has become a modern imaging technique in men with prostate cancer and biochemical relapse after local treatment with curative intent (radical prostatectomy, external beam/intensity-modulated radiation therapy, brachytherapy) in order to differentiate between local, locoregional and systemic relapse. Although 18F-choline PET/CT will probably be replaced by prostate-specific membrane antigen-PET/CT in the near future, the present paper by Rodada-Marina et al. [1] is important for daily routine because the authors attempt to define the current role of 18F-choline PET/CT in the diagnostic algorithm of men with relapsing PSA and to define specific patient cohorts in whom 18F-choline PET/CT might have a significant impact in the decision-making process regarding the most appropriate treatment.

Two issues are important to me when discussing the potential indication for performing new imaging studies in my patients with relapsing PSA: (1) whether the method is sensitive enough to detect a metastatic deposit at a given PSA serum concentration and (2) whether a positive finding using this imaging method would change my treatment recommendation. In this context, the current recommendation is 18F-choline PET/CT at a PSA serum concentration >1 ng/mL if a therapeutic consequence will be drawn [2]. If the patient would not be a candidate for a secondary local treatment option, such as salvage radiation therapy or salvage radical prostatectomy, but he would be treated with androgen deprivation therapy anyhow, none of the modern imaging studies would make sense.

In the present paper, a total of 233 patients from six different institutions were included in a retrospective study. One of the most important findings of this paper is that the detection rate was only 47.6%, despite relatively high mean and median trigger PSA serum levels of 5.3 and 2.8 ng/mL, respectively. The detection rates varied between 23.5 and 38.2% in men with PSA serum levels between <1 and 2–3 ng/mL and the detection only increased to 67% in men with PSA levels ≥3 ng/mL. Moreover, the authors identified that the best threshold for the trigger PSA level was 3.5 ng/mL, with a sensitivity and a specificity of 64 and 76%, respectively. With regard to PSA doubling time (PSA-DT), the best threshold was < 6 months, with a sensitivity and a specificity of 58% only. Based on these very high PSA serum levels at the time of imaging studies, which had the potential intent to select the most appropriate therapy, the majority of patients were already beyond the scope of secondary local therapy with curative intent [2, 3]. Furthermore, it was shown that patients with a Gleason score 8–10 and a PSA-DT of <6 months have a higher probability of having systemic disease – a fact which is well known already.

What do these data mean for clinical practice? There might be three clinical scenarios in which imaging studies might exert a significant impact on further treatment: (1) salvage radiation therapy in men with PSA relapse after radical prostatectomy (RP) [2, 3], (2) salvage RP after radiation therapy of the prostate [4] and (3) salvage pelvic lymphadenectomy in men with PSA relapse after RP or radiation therapy of the prostate [5]. In my view, the data underline the fact that imaging with 18F-choline PET/CT is not helpful in the first clinical scenario, early or late PSA relapse after RP. The clinician needs to start local salvage therapy, such as percutaneous radiation therapy, at a serum PSA concentration well below 0.5 ng/mL if a curative intent is the focus of treatment [2, 3]. Based on the current data, only one fifth of the patient cohort had a positive 18F-choline PET/CT finding even when considering aggressive biological features such as a high Gleason score, a rapid PSA-DT and a high PSA nadir after RP; therefore, PET/CT does not add significant additional diagnostic information in the individual patient so that it does not appear useful to perform 18F-choline PET/CT in men with low PSA levels at time of relapse. 18F-choline PET/CT might be helpful in the second clinical scenario to identify patients who will benefit from salvage RP. It has been shown that a PSA < 10 ng/mL and a PSA-DT >12 months at time of surgery are the most significant prognosticators for identifying organ-confined disease [4]. A positive detection rate for metastatic foci would be >75% in this scenario, underlining the indication for performing choline PET/CT. With regard to the third clinical scenario, it has been shown that a serum PSA <4 ng/mL and a slow PSA-DT represent prognostic markers for selecting men who most probably have locoregional relapse in the small pelvis and who will benefit the most from salvage lymphadenectomy [5]. Again, choline-PET/CT is indicated to exclude retroperitoneal or systemic disease and it should be performed before any salvage procedure.

In conclusion, the retrospective study performed by Rodado-Marina et al. [1] provides significant and clinically useful information with regard to the definition of a patient cohort that would benefit most from the performance of a choline PET/CT. This information should be considered when counselling patients with regard to the need for new imaging methods at the time of PSA relapse.

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Axel Heidenreich,

 

Department of Urology,Uniklinik RWTH University Aachen, Aachen, Germany

 

References

 

1 Rodado-Marina S, Coronado-Poggio M, Garcia-Vicente A et al. Clinical utility of 18F-flourocholine PET-CT in biochemical relapse of prostate cancer after radical treatment. Results of a multicentre study. BJU Int 2015. [Epub ahead of print]. doi: 10.1111/bju.12953

 

2 Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on Prostate Cancer. Part 2: screening, diagnosis, and local treatment with curative intent – update 2013. Eur Urol 2014; 65: 467–79

 

3Pfister D, Bolla M, Briganti A et al. Early salvage radiotherapy following radical prostatectomy. Eur Urol 2014; 65: 1034–43

 

4 Heidenreich A, Richter S, Th€uer D, Pfister D. Prognostic parameters, complications, and oncological and functional outcome of salvage radical prostatectomy for locally recurrent prostate cancer after 21rst-century radiotherapy. Eur Urol 2010; 57: 437–45

 

5 Rigatti P, Suardi N, Briganti A et al. Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol 2011; 60: 935–43

 

Article of the Week: Evaluating the proportion of tadalafil-treated patients with clinical improvement in LUTS associated with BPH

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Every Week the Editor-in-Chief selects the Article of the Week 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.

Finally, the third 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 Dr. Jonathan Rees, discussing the paper. 

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

Proportion of tadalafil-treated patients with clinically meaningful improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia – integrated data from 1499 study participants

John Curtis Nickel, Gerald B. Brock*, Sender Herschorn†, Ruth Dickson‡, Carsten Henneges§ and Lars Viktrup

 

Department of Urology, Queen’s University, Kingston, *University of Western Ontario, London, †Division of Urology, University of Toronto, ‡Eli Lilly Canada Inc., Toronto, ON, Canada, §Lilly Deutschland GmbH, Bad Homburg, Germany, and ¶Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA

 

Read the full article
OBJECTIVES

To evaluate the proportion of patients achieving clinically meaningful improvement of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) with tadalafil using two definitions of response.

PATIENTS AND METHODS

Post hoc integrated analysis of four placebo-controlled studies in men (aged ≥45 years; International Prostate Symptom Score [IPSS] of ≥13; maximum urinary flow rate [Qmax] of ≥4 to ≤15 mL/s) with BPH-LUTS randomised to tadalafil 5 mg (752 patients) or placebo (747) for 12 weeks after a 4-week placebo run-in. Responders were defined as having a total IPSS improvement of ≥3 points or ≥25% from randomisation to endpoint (Week 12). Response status was calculated per patient, and relative benefit and odds ratio (OR) with 95% confidence interval (CI) of tadalafil vs placebo was calculated using a logistic Generalised Mixed Model for Repeated Measures.

RESULTS

Tadalafil 5 mg once daily resulted in a significantly greater proportion of patients achieving a ≥3-point IPSS improvement (71.1% and 56.0% for tadalafil and placebo patients, respectively [OR 1.9, 95% CI 1.5, 2.4; P < 0.001]) and achieving a ≥25% improvement in total IPSS randomisation to endpoint (61.7% and 45.5% for tadalafil and placebo patients, respectively [OR 2.0, 95% CI 1.6, 2.5; P < 0.001]).

CONCLUSIONS

About two-thirds of tadalafil-treated patients achieve a clinically meaningful improvement in BPH-LUTS symptoms, based on two different definitions of responder status.

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Editorial: Patients not p-values

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A well powered study can attain statistical significance at a small effect size, but in real-life clinical practice, we do not routinely judge the success or failure of treatment based on the mean result for the hundreds of patients we have treated previously. Nor do we compare the response to treatment with what would have happened if we gave our patient a placebo; instead, clinical effectiveness is determined by the response of the individual patient seated across the desk in our clinic. In an ideal world, therefore, clinical significance, as well as statistical significance, should be built into study design and influence sample size and methodology in much the same way. In this way, we could attempt to assign objectivity to what is essentially a subjective metric: ‘did this treatment work for you?’

It is 25 years since the concept of ‘minimum clinically important difference’ (MCID) was first postulated [1] and almost 20 years since Barry et al. [2] applied this theory to LUTS and the IPSS in particular. MCID represents the smallest change as a result of treatment that is of clinical importance. In a measure such as blood pressure or diabetic control, this is the difference that makes a meaningful impact on complications, but in a quality-of-life field, such as measurement of urinary symptoms where we are predominantly treating the bother caused by the symptoms, the MCID is the smallest change that is noticeable to the patient. Barry et al. showed that a three-point improvement in IPSS is the minimum change required for a patient to notice a slight improvement in symptoms (five points correlating with a moderate improvement and eight points with marked improvement). For the IPSS quality-of-life item, the MCID is considered to be 0.5 points. This is based on two considerations: in other well studied questions with similar seven-point Likert scales, the MCIDs are usually ∼0.5, with the rule of thumb that the MCID is ∼0.5 of the standard deviation/one standard error of measurement. The 2010 National Institute for Health and Care Excellence LUTS in Men Guideline examined the concept of what constituted the MCID for flow rate changes; the evidence base is weak, but a change of 2 mL/s was taken as the MCID, based on the evidence available and expert opinion [3]. A change of three points in total IPSS, however, whilst noticeable, does not necessarily imply a significant improvement in overall or disease-specific quality of life. Furthermore, in a patient with severe symptoms, an improvement of three points may represent a much smaller change than in a patient with milder symptoms at baseline, and for this reason, an improvement in IPSS of ≥25% from baseline has also been proposed as a threshold for clinically meaningful improvement.

The study by Nickel et al. [4] is a rare example of an attempt to integrate the concept of MCID into LUTS trial reporting, analysing the proportion of men with LUTS/BPH, treated with tadalafil 5 mg once daily, who achieved a meaningful improvement in symptoms based on changes in both actual and percentage IPSS. This analysis again shows the power of placebo in LUTS treatment, with approximately half the patients in placebo arms of the four studies achieving the MCID on the IPSS. For those treated with tadalafil, a greater proportion achieved the MCID, with 71.1% seeing an improvement of ≥3 points on the IPSS, and 61.7% a ≥25% change in total IPSS. This benefit over placebo was greater when more demanding clinical thresholds were used, e.g. 50 or 75% improvement on IPSS.

It is encouraging to see a paper that reports clinical significance, but whilst of interest, the study is a post hoc analysis of four trials designed to test tadalafil vs tamsulosin or placebo, for licensing approval, and not a trial designed specifically to measure the clinical significance of changes in symptoms. It is a useful reminder to urologists, however, of the concept of MCID, which despite being well established is not widely known. MCID should be incorporated into the analysis of any results based on patient-reported outcomes [5] where the clinical significance of the results may not be immediately apparent to the clinician.

Read the full article
by Jonathan Rees

 

Backwell & Nailsea Medical Group, Nailsea, North Somerset, UK

 

References

 

1 Jaeschke R, Singer J, Guyatt G. Measurement of health status: ascertaining the minimally clinically important difference. Control Clin Trials 1989; 10: 407–41

 

2 Barry MJ, Williford WO, Chang Y et al. Benign prostatic hyperplasia specific health 30 status measures in clinical research: how much change in the American Urological 31 Association symptom index and the benign prostatic hyperplasia impact index is 32 perceptible to patients? J Urol 1995; 154: 1770–4

 

3 National Institute for Health and Clinical Excellence. The management of lower urinary tract symptoms in men. (Clinical Guideline 97.) 2010. https://guidance.nice.org.uk/CG97

 

4 Nickel JC, Brock GB, Herschorn S, Dickson R, Henneges C, Viktrup L. Proportion of tadalafil-treated patients with clinically meaningful improvement in lower 1 urinary tract symptoms associated with benign prostatic hyperplasia – integrated data 2 from 1499 study participants. BJU Int 2015; 115: 815–21

 

5 McGlothin A, Lewis R. Minimal clinically important difference: defining what really matters to patients. JAMA 2014; 312: 1342–3

 

Video: Patients not p-values

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Proportion of tadalafil-treated patients with clinically meaningful improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia – integrated data from 1499 study participants

John Curtis Nickel, Gerald B. Brock*, Sender Herschorn†, Ruth Dickson‡, Carsten Henneges§ and Lars Viktrup

 

Department of Urology, Queen’s University, Kingston, *University of Western Ontario, London, †Division of Urology, University of Toronto, ‡Eli Lilly Canada Inc., Toronto, ON, Canada, §Lilly Deutschland GmbH, Bad Homburg, Germany, and ¶Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA

 

Read the full article
OBJECTIVES

To evaluate the proportion of patients achieving clinically meaningful improvement of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) with tadalafil using two definitions of response.

PATIENTS AND METHODS

Post hoc integrated analysis of four placebo-controlled studies in men (aged ≥45 years; International Prostate Symptom Score [IPSS] of ≥13; maximum urinary flow rate [Qmax] of ≥4 to ≤15 mL/s) with BPH-LUTS randomised to tadalafil 5 mg (752 patients) or placebo (747) for 12 weeks after a 4-week placebo run-in. Responders were defined as having a total IPSS improvement of ≥3 points or ≥25% from randomisation to endpoint (Week 12). Response status was calculated per patient, and relative benefit and odds ratio (OR) with 95% confidence interval (CI) of tadalafil vs placebo was calculated using a logistic Generalised Mixed Model for Repeated Measures.

RESULTS

Tadalafil 5 mg once daily resulted in a significantly greater proportion of patients achieving a ≥3-point IPSS improvement (71.1% and 56.0% for tadalafil and placebo patients, respectively [OR 1.9, 95% CI 1.5, 2.4; P < 0.001]) and achieving a ≥25% improvement in total IPSS randomisation to endpoint (61.7% and 45.5% for tadalafil and placebo patients, respectively [OR 2.0, 95% CI 1.6, 2.5; P < 0.001]).

CONCLUSIONS

About two-thirds of tadalafil-treated patients achieve a clinically meaningful improvement in BPH-LUTS symptoms, based on two different definitions of responder status.

Read more articles of the week

Article of the Week: Psychometric evaluation of PRO data for the treatment of Peyronie’s disease

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Every Week the Editor-in-Chief selects the Article of the Week 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.

Finally, the third 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 Dr. Franklin Emmanuel Kuehhas, discussing his paper. 

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

International multicentre psychometric evaluation of patient-reported outcome data for the treatment of Peyronie’s disease

Verena Kueronya, Arkadius Miernik*, Slavisa Stupar†, Vladimir Kojovic‡, Georgios Hatzichristodoulou§, Paulo H. Egydio, Georgi Tosev**, Marco Falcone††, Francesco De Luca‡‡, Demir Mulalic†, Miroslav Djordjevic‡, Martin Schoenthaler*, Christian Fahr* and Franklin E. Kuehhas† Department of Obstetrics and Gynecology,

 

†Department of Urology, Medical University of Vienna, Vienna, Austria, *Departments of Urology, Medical University of Freiburg, Freiburg, §Departments of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, **Departments of Urology, Medical University of Heidelberg, Heidelberg, Germany, ‡School of Medicine, University of Belgrade, Belgrade, Serbia, Centre for Peyronie’s Disease Reconstruction, Sao Paulo, Brazil, ††Department of Urology, Medical University of Turin, Turin, Italy, and ‡‡Institute of Urology, University College London, London, UK

 

Read the full article

OBJECTIVE

To compare patient-reported outcomes (PROs) of surgical correction of Peyronie’s disease (PD) with the Nesbit procedure, plaque incision and grafting, and the insertion of a malleable penile implant after surgical correction of penile curvature.

PATIENTS AND METHODS

We performed a retrospective review of men who underwent surgical correction of PD between January 2010 and December 2012 at six international centres. Treatment-related PROs and satisfaction were evaluated with a non-validated questionnaire.

RESULTS

The response rate to the questionnaire was 70.9%, resulting in a study cohort of 206 patients. The Nesbit procedure, plaque incision with grafting, or implantation of a malleable penile prosthesis was performed in 50, 48, and 108 patients, respectively. Overall, 79.1% reported a subjective loss of penile length due to PD preoperatively (range 2.1–3.2 cm). Those patients treated with a malleable penile implant reported the greatest subjective penile length loss, due to PD. A subjective loss of penile length of >2.5 cm resulted in reduced preoperative sex ability. Postoperatively, 78.0%, 29.2% and 24.1% patients in the Nesbit, grafting, and implant groups reported a postoperative, subjective loss of penile length (range 0.4–1.2 cm), with 86.3%, 78.6%, and 82.1% of the patients in each group, respectively, being bothered by the loss of length.

CONCLUSIONS

Penile length loss due to PD affects most patients. Further penile length loss due to the surgical correction leads to bother among the affected patients, irrespective of the magnitude of the loss. The Nesbit procedure was associated with the highest losses in penile length. In patients with PD and severe erectile dysfunction, a concomitant lengthening procedure may be offered to patients to help overcome the psychological burden caused by the loss of penile length.

Read more articles of the week

 

Editorial: The impact of the surgical correction of Peyronie’s disease – a patient’s perspective

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Peyronie’s disease (PD) is an acquired benign connective tissue disorder of the tunica albuginea of the penis that leads to the formation of fibrous inelastic plaques. As a result of pain, worsening quality of erections, penile shortening and deformity, the quality of life of both the patient and their partner may be significantly affected, and this may lead to depression, low self-esteem and relationship difficulties [1].

At present, surgery represents the ‘gold standard’ treatment when PD is stable, and should be offered to guarantee a penis straight and rigid enough to allow penetrative intercourse.

The flow chart in the 2010 guidelines on PD indicates the type of surgery that should be offered according to the preoperative quality of the erection, degree of deformity and penile length, but patient perception of preoperative penile shortening is not taken into consideration [2]. Penile shortening does play an important part, however, with regard to postoperative patient satisfaction, as confirmed by Akin-Olugbade et al. [3], whose series of patients with PD reported the lowest satisfaction rates after penile prosthesis implantation.

According to the present series by Kueronya et al. [4], in which patient-perceived pre- and postoperative penile length loss in patients with PD was evaluated, 79.1% of patients perceived a degree of length loss attributable to PD, and a subjective loss of length of >2.5 cm translated into reduced ability with regard to sexual intercourse. In particular, patients who underwent penile prosthesis implantation reported more significant perceived shortening. This is not surprising, as patients with larger plaques, more severe forms of PD and fibrosis are more likely to have erectile dysfunction and ultimately to require a penile prosthesis implantation. Among patients who did not undergo penile prosthesis implantation, those requiring Nesbit plication reported less preoperative shortening than those requiring plaque incision and grafting, as the latter group presented with more severe deformities.

Further penile length loss caused by the surgical correction leads to bother to the patients, irrespective of the magnitude of the loss. The message from the present series by Kueronya et al. is that, to achieve higher postoperative satisfaction rates in this unfortunate cohort of patients, the choice of the type of surgery should take into consideration patient’s perceived preoperative penile shortening and not be based solely on the 2010 PD guidelines algorithm, because ultimately patients wish to obtain full restoration of the shape and size of penis they had before the onset of PD [2].

As patient’s perceived penile length plays such an important role in a patient’s postoperative satisfaction and because patients undergoing penile prosthesis implantation are those who have lost more length, length restoration should be offered simultaneously with penile prosthesis implantation [5, 6].

Kueronya et al. should be congratulated for their work, which is the first series evaluating patient’s perceived penile shortening and may represent a significant step towards the restoration of an adequate sex life in patients with PD.

Read the full article
Giulio Garaffa and David J. Ralph

 

St Peter’s Andrology and the Institute of Urology, University College London Hospitals, London, UK

 

References

 

1 Rosen R,Catania J, Lue T et al. Impact of Peyronie’s disease on sexual and psychosocial functioning: qualitative findings in patients and controls. J Sex Med 2008; 5: 1977–84

 

2 Ralph D, Gonzalez-Cadavid N , Mirone V et al. The management of Peyronie’s Disease: evidence-based 2010 guidelines. J Sex Med 2010; 7: 2359–74

 

3 Akin-Olugbade O, Parker M, Guhring P, Mulhall J. Determinants of patient satisfaction following penile prosthesis surgery. J Sex Med 2006; 3: 743–8

 

4 Kueronya V, Miernik A, Stupar S et al. International multicenter psychometric evaluation of patient reported outcome data for the treatment of Peyronie’s Disease. BJU Int 2015; 115: 822–8

 

5 Sansalone S, Garaffa G, Djinovic R et al. Simultaneous penile lengthening and penile prosthesis implantation in patients with Peyronie’s Disease, refractory erectile dysfunction and severe penile shortening. J Sex Med 2012; 9: 316–21

 

6 Egydio PH, Kuehhas FE, Sansalone S. Penile girth and length restoration in severe Peyronie’s Disease using circular and longitudinal grafts. BJU Int 2013; 111 (4 Pt B): E213–9

 

Video: Peyronie’s disease treatment – psychometric evaluation of PRO data

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International multicentre psychometric evaluation of patient-reported outcome data for the treatment of Peyronie’s disease

Verena Kueronya, Arkadius Miernik*, Slavisa Stupar†, Vladimir Kojovic‡, Georgios Hatzichristodoulou§, Paulo H. Egydio, Georgi Tosev**, Marco Falcone††, Francesco De Luca‡‡, Demir Mulalic†, Miroslav Djordjevic‡, Martin Schoenthaler*, Christian Fahr* and Franklin E. Kuehhas† Department of Obstetrics and Gynecology,

 

†Department of Urology, Medical University of Vienna, Vienna, Austria, *Departments of Urology, Medical University of Freiburg, Freiburg, §Departments of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, **Departments of Urology, Medical University of Heidelberg, Heidelberg, Germany, ‡School of Medicine, University of Belgrade, Belgrade, Serbia, Centre for Peyronie’s Disease Reconstruction, Sao Paulo, Brazil, ††Department of Urology, Medical University of Turin, Turin, Italy, and ‡‡Institute of Urology, University College London, London, UK
Read the full article
OBJECTIVE

To compare patient-reported outcomes (PROs) of surgical correction of Peyronie’s disease (PD) with the Nesbit procedure, plaque incision and grafting, and the insertion of a malleable penile implant after surgical correction of penile curvature.

PATIENTS AND METHODS

We performed a retrospective review of men who underwent surgical correction of PD between January 2010 and December 2012 at six international centres. Treatment-related PROs and satisfaction were evaluated with a non-validated questionnaire.

RESULTS

The response rate to the questionnaire was 70.9%, resulting in a study cohort of 206 patients. The Nesbit procedure, plaque incision with grafting, or implantation of a malleable penile prosthesis was performed in 50, 48, and 108 patients, respectively. Overall, 79.1% reported a subjective loss of penile length due to PD preoperatively (range 2.1–3.2 cm). Those patients treated with a malleable penile implant reported the greatest subjective penile length loss, due to PD. A subjective loss of penile length of >2.5 cm resulted in reduced preoperative sex ability. Postoperatively, 78.0%, 29.2% and 24.1% patients in the Nesbit, grafting, and implant groups reported a postoperative, subjective loss of penile length (range 0.4–1.2 cm), with 86.3%, 78.6%, and 82.1% of the patients in each group, respectively, being bothered by the loss of length.

CONCLUSIONS

Penile length loss due to PD affects most patients. Further penile length loss due to the surgical correction leads to bother among the affected patients, irrespective of the magnitude of the loss. The Nesbit procedure was associated with the highest losses in penile length. In patients with PD and severe erectile dysfunction, a concomitant lengthening procedure may be offered to patients to help overcome the psychological burden caused by the loss of penile length.

Read more articles of the week

Editorial: Selecting the right α-blocker – is silodosin your best option?

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A significant proportion of aging men will have bothersome LUTS and will eventually seek help for this problem. Various medical therapies are available to help aleviate these symptoms. Amongst the various treatments, α-blockers are some of the most widely used drugs. Novara et al. [1] recently published a report on the efficacy and safety of silodosin in a pooled analysis of individual patient data from three registrational randomized controlled trials comparing silodosin and placebo in patients with LUTS. Their study contributes pertinent information to aid the clinician in determining which α-blocker is best suited for specific patients with LUTS.

In the current study, patients were subdivided into groups in order to better understand which patient would benefit most from the use of silodosin [2]. In addition, the article examines the safety of silodosin in these same distinct patient groups. With regard to efficacy, silodosin was significantly more effective than placebo in improving all IPSS-related variables and maximum urinary flow rate, regardless of the patient’s age. When comparing the efficacy of silodosin in different age groups, no difference was observed for any of the IPSS variables, whereas patients aged <65 years had a statistically significantly greater maximum urinary flow rate.

With regard to safety, silodosin was associated with a significantly higher adverse event (AE) rate compared with placebo. When comparing the safety of silodosin in patients aged <65 years and >65 years, the overall AE rate, ejaculatory dysfunction and discontinuation rate attributable to AEs were all higher in the younger age group. Interestingly, in patients with concomitant use of antihypertensive drugs, the use of silodosin was not associated with a higher risk of either dizziness or orthostatic hypotension.

In a previous study by the same authors, no clinically relevant or statistically significant differences with regard to diastolic blood pressure, systolic blood pressure or heart rate in patients taking silodosin as compared to placebo were found [3]; however, a minor statistically significant difference vs placebo was observed with tamsulosin. The present study by Novara et al. [2] further supports the belief that silodosin is a safe drug from a cardiovascular standpoint.

From a sexual standpoint, silodosin does not seem to perform as well. In the present study, patients in the silodosin group had significantly more adverse events as compared with the placebo group. Retrograde ejaculation was by far the most common side effect affecting 32.8% of patients aged <65 years vs 0.9% in the placebo group. Similarly, in a study by Chapple et al. [3], as many as 14.2% of patients in the silodosin treatment group had ejaculatory dysfunction, compared with 2.1 and 1.1% of patients in the tamsulosin and placebo treatment groups, respectively. Although the percentage of patients who discontinued treatment because of treatment-emergent AEs in the present study was small and not significantly different among all treatment groups, one might hypothesize that over a longer follow-up period, such a prevalent side effect could be responsible for a higher discontinuation rate. Consequently, it should be kept in mind that for patients desiring to maintain antegrade ejaculation, or who are bothered by treatment-onset ejaculatory dysfunction, especially younger patients, silodosin might not be the best treatment option. Furthermore, it should be recognized that some patients would potentially accept a reduction in treatment efficacy to preserve ejaculation [4].

With regard to clinical outcomes, few published papers comparing tamsulosin with silodosin are available [5, 6]. One article found no clinically significant difference between the two α-blockers [5] whereas the other, which was a post hoc analysis, found a marginal clinical benefit for silodosin over tamsulosin [4]. Unfortunately, head-to-head trials are not forthcoming, so it will not be possible to determine if one α-blocker is clinically better than the other. Furthermore, the present study, because it lacked an active control arm, did not compare silodosin with tamsulosin, which leaves something to be desired.

In conclusion, careful consideration should be given to specific patient characteristics such as age and comorbidities, along with personal preferences towards sexual function when offering patients α-blockers for treatment of LUTS.

Read the full article
Hugo Lavigueur-Blouin and Naeem Bhojani

 

Department of Urology, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada

 

References

 

1 Novara G, Chapple CR, Montorsi F. A pooled analysis of individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). BJU Int 2014; 114: 427–33

 

2 Novara G, Chapple CR, Montorsi F. Individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH): subgroup analyses of efficacy and safety data. BJU Int 2015; 115: 802–4

 

3 Chapple CR, Montorsi F, Tammela TL et al. Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. Eur Urol 2011; 59: 342–52

 

4 Sturch P, Woo HH, McNicholas T, Muir G. Ejaculatory dysfunction after treatment for lower urinary tract symptoms: retrograde ejaculation or retrograde thinking? BJU Int 2014. doi: 10.1111/bju.12868

 

5 Montorsi F. Profile of Silodosin. Eur Urol Suppl 2010; 9: 491–5

 

6 Novara G, Tubaro A, Sanseverino R et al. Systematic review and meta-analysis of randomized controlled trials evaluating silodosin in the treatment of non-neurogenic male lower urinary tract symptoms suggestive of benign prostatic enlargement. World J Urol 2013; 31: 997–1008

 

Video: Is silodosin your best option when selecting the right α-blocker?

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A significant proportion of aging men will have bothersome LUTS and will eventually seek help for this problem. Various medical therapies are available to help aleviate these symptoms. Amongst the various treatments, α-blockers are some of the most widely used drugs. Novara et al. [1] recently published a report on the efficacy and safety of silodosin in a pooled analysis of individual patient data from three registrational randomized controlled trials comparing silodosin and placebo in patients with LUTS. Their study contributes pertinent information to aid the clinician in determining which α-blocker is best suited for specific patients with LUTS.

In the current study, patients were subdivided into groups in order to better understand which patient would benefit most from the use of silodosin [2]. In addition, the article examines the safety of silodosin in these same distinct patient groups. With regard to efficacy, silodosin was significantly more effective than placebo in improving all IPSS-related variables and maximum urinary flow rate, regardless of the patient’s age. When comparing the efficacy of silodosin in different age groups, no difference was observed for any of the IPSS variables, whereas patients aged <65 years had a statistically significantly greater maximum urinary flow rate.

With regard to safety, silodosin was associated with a significantly higher adverse event (AE) rate compared with placebo. When comparing the safety of silodosin in patients aged <65 years and >65 years, the overall AE rate, ejaculatory dysfunction and discontinuation rate attributable to AEs were all higher in the younger age group. Interestingly, in patients with concomitant use of antihypertensive drugs, the use of silodosin was not associated with a higher risk of either dizziness or orthostatic hypotension.

In a previous study by the same authors, no clinically relevant or statistically significant differences with regard to diastolic blood pressure, systolic blood pressure or heart rate in patients taking silodosin as compared to placebo were found [3]; however, a minor statistically significant difference vs placebo was observed with tamsulosin. The present study by Novara et al. [2] further supports the belief that silodosin is a safe drug from a cardiovascular standpoint.

From a sexual standpoint, silodosin does not seem to perform as well. In the present study, patients in the silodosin group had significantly more adverse events as compared with the placebo group. Retrograde ejaculation was by far the most common side effect affecting 32.8% of patients aged <65 years vs 0.9% in the placebo group. Similarly, in a study by Chapple et al. [3], as many as 14.2% of patients in the silodosin treatment group had ejaculatory dysfunction, compared with 2.1 and 1.1% of patients in the tamsulosin and placebo treatment groups, respectively. Although the percentage of patients who discontinued treatment because of treatment-emergent AEs in the present study was small and not significantly different among all treatment groups, one might hypothesize that over a longer follow-up period, such a prevalent side effect could be responsible for a higher discontinuation rate. Consequently, it should be kept in mind that for patients desiring to maintain antegrade ejaculation, or who are bothered by treatment-onset ejaculatory dysfunction, especially younger patients, silodosin might not be the best treatment option. Furthermore, it should be recognized that some patients would potentially accept a reduction in treatment efficacy to preserve ejaculation [4].

With regard to clinical outcomes, few published papers comparing tamsulosin with silodosin are available [5, 6]. One article found no clinically significant difference between the two α-blockers [5] whereas the other, which was a post hoc analysis, found a marginal clinical benefit for silodosin over tamsulosin [4]. Unfortunately, head-to-head trials are not forthcoming, so it will not be possible to determine if one α-blocker is clinically better than the other. Furthermore, the present study, because it lacked an active control arm, did not compare silodosin with tamsulosin, which leaves something to be desired.

In conclusion, careful consideration should be given to specific patient characteristics such as age and comorbidities, along with personal preferences towards sexual function when offering patients α-blockers for treatment of LUTS.

Read the full article
Hugo Lavigueur-Blouin and Naeem Bhojani

 

Department of Urology, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada

 

References

 

1 Novara G, Chapple CR, Montorsi F. A pooled analysis of individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). BJU Int 2014; 114: 427–33

 

2 Novara G, Chapple CR, Montorsi F. Individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH): subgroup analyses of efficacy and safety data. BJU Int 2015; 115: 802–4

 

3 Chapple CR, Montorsi F, Tammela TL et al. Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. Eur Urol 2011; 59: 342–52

 

4 Sturch P, Woo HH, McNicholas T, Muir G. Ejaculatory dysfunction after treatment for lower urinary tract symptoms: retrograde ejaculation or retrograde thinking? BJU Int 2014. doi: 10.1111/bju.12868

 

5 Montorsi F. Profile of Silodosin. Eur Urol Suppl 2010; 9: 491–5

 

6 Novara G, Tubaro A, Sanseverino R et al. Systematic review and meta-analysis of randomized controlled trials evaluating silodosin in the treatment of non-neurogenic male lower urinary tract symptoms suggestive of benign prostatic enlargement. World J Urol 2013; 31: 997–1008

 

Article of the Month: Have TRP channels fulfilled their promise in LUTS?

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Every Month the Editor-in-Chief selects the 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.

Finally, the third post under the Article of the Month heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Wouter Everaerts, discussing his paper. 

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

Transient receptor potential channel modulators as pharmacological treatments for lower urinary tract symptoms (LUTS): myth or reality?

Yves Deruyver*‡¶, Thomas Voets†¶, Dirk De Ridder*‡¶ and Wouter Everaerts*§¶

 

*Laboratory of Experimental Urology, Department of Development and Regeneration,† Laboratory for Ion Channel Research, Department of Molecular Cell Biology, KU Leuven, ‡University Hospitals Leuven, TRP Research Platform Leuven (TRPLe), Leuven, Belgium, and §Royal Melbourne Hospital, Melbourne, Australia

 

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Transient receptor potential (TRP) channels belong to the most intensely pursued drug targets of the last decade. These ion channels are considered promising targets for the treatment of pain, hypersensitivity disorders and lower urinary tract symptoms (LUTS). The aim of the present review is to discuss to what extent TRP channels have adhered to their promise as new pharmacological targets in the lower urinary tract (LUT) and to outline the challenges that lie ahead.

  • TRP vanilloid 1 (TRPV1) agonists have proven their efficacy in the treatment of neurogenic detrusor overactivity (DO), albeit at the expense of prolonged adverse effects as pelvic ‘burning’ pain, sensory urgency and haematuria.
  • TRPV1 antagonists have been very successful in preclinical studies to treat pain and DO. However, clinical trials with the first generation TRPV1 antagonists were terminated early due to hyperthermia, a serious, on-target, side-effect.
  • TRP vanilloid 4 (TRPV4), TRP ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) have important sensory functions in the LUT. Antagonists of these channels have shown their potential in pre-clinical studies of LUT dysfunction and are awaiting clinical validation.
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