Tag: Editorial

Posts

Scientific impact and beyond

December 1, 2015/1 Comment/by Prokar Dasgupta

After a constant upward trajectory for 3 years, in 2015 the BJUI achieved an impact factor (IF) of 3.53, the highest ever in its history. Complacency is not in our DNA and we hope to achieve much more. We set out to become the most read surgical journal on the web and as part of that initiative have just launched our Android app in addition to the existing iPhone and iPad app. But our true impact beyond the IF, lies perhaps in the Altmetric score.

Altmetric is a score of the impact of (or perhaps better, the attention attained by) articles, based on mentions over a period of time in online channels such as news outlets, science blogs, Twitter, Facebook, Sina Weibo and Wikipedia, amongst others. The automated algorithm’s calculation of an article’s score applies weighting to the sources, such that a mention on a news outlet is weighted 8, or in a science blog 5, whereas a Twitter mention is only weighted 1, and a Facebook mention 0.25. News outlet scores are also tiered by their reach, re-tweets score less than original tweets, and bias is accounted for, e.g. tweets by independent researchers count more than a tweet by the journal that published the article.

The results are visualized as the ‘Altmetric donut’ with the calculated score in the centre. In the donut the different colours represent the different channels; so, for example Twitter is cyan, Facebook is dark blue, Blogs (including Weibo) are orange, News outlets red, Google+ is magenta, Video is pale green, Reddit is pale blue and Wikipedia is dark grey. The proportion of the donut that is shown in each colour generally reflects how much of the score was contributed to by that channel, but when many channels need to be represented then each is given a segment as is seen in the rainbow donut for our ‘Am I Normal’ article [Veale et al].

To give some context to the phenomenal level of interest in the ‘Am I Normal’ article, which at the time of writing boasts a score of 1034, most articles attain a score of 3 or under, and a score of 9 is sufficient to put an article in the top 10% of all 4,386,073 that Altmetric has scored. ‘Am I Normal’ is, perhaps unsurprisingly, in the top 1% of all articles scored.

Our other highly citable innovation is the BJUI Guideline of Guidelines (GOGs), which have made access to, and the understanding of, often conflicting urological guidelines a lot easier. Along with our other guidelines on chronic prostatitis [Rees et al] and continence [Tse et al], they will all be available in early 2016 as a virtual issue of GOGs [Loeb; Ziemba & Matlaga; Wollin & Makarov; Syan & Brucker] in a single repository on our web journal. Completely free, of course!

Prokar Dasgupta, Editor-in-Chief, BJUI
Scott Millar, Managing Editor, BJUI
Jo Wixon, Publisher, John Wiley and Sons Ltd

Editorial: More Nomograms or Better Lymph node dissection – What do we need in Prostate Cancer?

November 25, 2015/by Martin Spahn

The publication of nomograms to predict radical prostatectomy (RP) outcome using preoperative parameters were important steps in urological oncology. Abdollah et al. [1], in this issue of BJU International, present a new nomogram to predict specimen-confined disease (SCD; pT2–3a, pN0 R0) in men with high-risk prostate cancer undergoing pelvic lymph node dissection (PLND) and robot-assisted RP (RARP). They used statistical logistic regression to measure the impact of various preoperatively available clinicopathological parameters on the likelihood of pathological outcome and tumour recurrence. The final nomogram accurately identified SCD (pT2–3a, pN0 R0) in 76% of the patients. It is intuitive that these patients have good long-term oncological outcomes after surgery. Consequently, Abdollah et al. found excellent 8-year cancer-specific survival rates in these patients. Because nomograms provide individualised risk prediction for patients in an easily applicable manner, they have become very popular among clinicians. Nomograms are now being applied for almost every aspect of prostate cancer. These are freely available and both patients and physicians are encouraged to use them.

Although nomograms undoubtedly have improved our perspective of disease behaviour and individual patient prediction, several key questions remain. First, how good are the input data to a nomogram? Abdollah et al. [1] evaluated 810 patients with high-risk prostate cancer treated in a single large centre between 2003 and 2012. Impressively, more than half of the patients (55%) harboured SCD at RARP. Such a high chance of having SCD will probably encourage many physicians and patients to choose surgery, even without using a nomogram, because this approach may avoid the need for hormonal treatment, which is obligatory for radiation therapy in high-risk prostate cancer. Second, is the predictive accuracy safe within clinical practice? Most nomograms using clinicopathological data generate predictive accuracies within the range of 75–90% (including the nomogram presented by Abdollah et al. [1]). It is of special importance to consider that 64/447 (14%) of the patients with SCD in the series reported by Abdollah et al. [1] received salvage treatment, which was initiated after a median (interquartile range, IQR) of 4.8 (1.4–9.3) months, and the indication to initiate this salvage therapy was PSA recurrence. Obviously, these patients did not have specimen confined disease and were misclassified. In this case, one might postulate a persistence of nodal disease, given an inadequate extent of PLND. Abdollah et al. [1] reported on a median (IQR) of 5 (3.0–11.0) lymph nodes removed.

In their landmark paper on extended PLND (ePLND) in cadavers, Weingartner et al. [2] demonstrated that a mean lymph node yield of 20 serves as a guideline for sufficient ePLND. More than 10 years ago, Heidenreich et al. [3] reported on a 15% higher rate of lymph node metastasis detection when comparing ePLND with the standard LND (obturator). Bader et al. [4] provided further evidence that an ePLND is needed to provide adequate clinical staging and potential therapeutic benefit. Of 365 patients with clinically localised prostate cancer, 88 (24%) had positive lymph nodes. In this series, a pelvic LND that spared the internal iliac bed would have left 58% of patients with positive nodes with residual disease and 19% would have been incorrectly staged as lymph node-negative for cancer. These data were recently confirmed by several authors when analysing retrospective series. Furthermore, Seiler et al. [5] updated their series of 88 patients and recently reported on the long-term outcome after a median follow-up of 15.6 years. They showed that 18% of those patients with one positive node remained biochemical recurrence free, 28% showed biochemical recurrence only, and 54% had clinical progression. Of these 39 patients, 57% never required deferred androgen-deprivation therapy. In contrast, patients with multiple positive nodes are likely to experience rapid progression and, thus, may benefit from early adjuvant therapies. International clinical practice guidelines recommend the performance of an anatomically ePLND at RP in men with high-risk prostate cancer, for both staging and therapeutic purposes.

Nowadays, most urologists claim to perform an ePLND. However, a recent analysis among 50 671 men who were surgically treated with RP from 2010 to 2011 in the USA showed that, overall, only 69.3% of the high-risk patients underwent concomitant PLND [6]. Surgical approach and hospital characteristics were associated with treatment with PLND and detection of lymph node metastasis. More specifically, patients with prostate cancer undergoing open RP or surgically treated at high-volume centres were more likely to undergo PLND than those undergoing RARP or surgically treated at low-volume centres.

Despite the strong evidence that ePLND positively affects survival in men with limited lymph node involvement, this procedure is not commonly performed. The reasons for this are multiple and include expertise, stage migration and functional and oncological outcomes, as well as economics and the introduction of laparoscopic and laparoscopic RARP. However, this is no reason not to offer the patient, if possible, an operation which has the highest chance of cure

Read the full article

Martin Spahn

Department of Urology, University Hospital Bern , Inselspital, Bern, Switzerland

References

1 Abdollah F, Klett DE, Sood A et al. Predicting pathological outcomes in patients undergoing robot-assisted radical prostatectomy for high- risk prostate cancer: a preoperative nomogram. BJU Int 2014; 116: 703–12

2 Weingartner K, Ramaswamy A, Bittinger A, Gerharz EW, Voge D, Riedmiller H. Anatomical basis for pelvic lymphadenectomy in prostate cancer: results of an autopsy study and implications for the clinic. J Urol 1996; 156: 1969–71

3 Heidenreich A, Varga Z, Von Knobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol 2002; 167: 1681–6

4 Bader P, Burkhard FC, Markwalder R, Studer UE. Is a limited lymph node dissection an adequate staging procedure for prostate cancer? J Urol 2002; 168: 514–8

5 Seiler R, Studer UE , Tschan K, Bader P, Burkhard FC. Removal of limited nodal disease in patients undergoing radical prostatectomy: long-term results conﬁrm a chance for cure. J Urol 2014; 191: 1280–5

6 Wang EH, Yu JB, Gross CP et al. Variation in pelvic lymph node dissection among patients undergoing radical prostatectomy by hospital characteristics and surgical approach: results from the National Cancer Database. J Urol 2015; 193: 820–5.

Editorial: Does a positive margin always mandate adjuvant radiotherapy?

November 18, 2015/by Peter Albertsen

The appropriate treatment for clinically localized prostate cancer continues to generate controversy. For men with low grade disease it is unclear whether surgery or radiation therapy provides a survival advantage over active surveillance, and among men with high grade disease it is unclear how many derive a substantial benefit from either intervention. No trial has yet to compare surgery and radiation with observation, but the recent update of the Scandinavian Prostate Cancer Group 4 study suggests that radical prostatectomy provides a significant survival advantage for younger men with intermediate grade disease [1].

Unfortunately, many men undergoing radical prostatectomy are not cured of their disease. The Scandinavian Prostate Cancer Group 4 study has shown that as many as 26% of men undergoing surgery developed distant metastases and 18% died from their disease after a median follow-up of 13 years. For this reason many clinicians recommend additional radiation therapy for those men undergoing surgery who are at high risk of disease recurrence. Three randomized trials now support the use of radiation therapy in this setting. Two have shown lower rates of biochemical progression and one has shown improved distant metastases-free survival and overall survival [2-4]. These trials compared the use of adjuvant radiation therapy with observation. Some clinicians, however, are reluctant to refer patients for radiation therapy because of concerns about its potential impact on quality of life. This is especially true for those patients who have yet to show any evidence of biochemical recurrence.

In a manuscript published in this month’s BJUI, Hsu et al. [5] have turned to a large national prostate cancer registry that has accrued men with newly diagnosed prostate cancer since 1995. They evaluated the long-term outcomes of these men to gain insights into whether a delay in the initiation of radiation therapy compromises survival. Their findings suggest that delaying the initiation of radiation therapy until there is evidence of biochemical recurrence does not seriously compromise long-term outcomes and avoids radiation in some men who are never destined to have disease progression.

The authors are appropriately cautious with their conclusions and clearly recognize the limitations of a non-randomized study. In a registry study it is impossible to control adequately for selection biases. Men receiving adjuvant therapy had no evidence of biochemical recurrence at the time radiation was started. This group of men included both men who were destined to have disease progression and men who were destined to maintain an undetectable PSA. This differs from the men receiving salvage radiation therapy. All men receiving salvage radiation had evidence of disease progression and therefore their tumour burden and their long-term prognosis was probably worse when compared with men receiving adjuvant therapy. Despite this selection bias, men initiating salvage radiation when their postoperative PSA level was still <1.0 ng/mL had similar long-term outcomes when compared with the men receiving adjuvant radiation. Men with postoperative PSA levels >1.0 ng/mL had a much higher risk of aggressive disease and a worse outcome.

Ideally, the question about the timing of postoperative radiation would be subjected to a randomized trial. Until then, the information provided by Hsu et al. provides strong clinical support for a practical approach to the question of who should receive postoperative radiation. Men who are clearly at high risk of disease progression, which includes men with Gleason 8–10 disease and those with extensive margin positive disease and seminal vesicle invasion, should probably receive adjuvant radiation therapy as soon as they have recovered from surgery. For men with Gleason 7 disease or those men who have focal margin-positive disease it may make sense to monitor postoperative PSA levels closely and refer men for postoperative radiation when there is evidence of biochemical progression and before the PSA level reaches 1.0 ng/mL. This approach would spare some men the need for additional treatment and would defer treatment for many years in others. Men who are eventually found to have biochemical recurrence should feel reasonably comfortable that the delay in initiating radiation therapy is unlikely to have caused any significant compromise of their long-term outcome and probably improved their quality of life.

Large case series analyses frequently have selection biases that confound conclusions. In this instance the authors have cautiously interpreted a large community-based registry to gain a valuable insight into the management of localized prostate cancer. Their analysis provides appropriate support for their conclusions.

Read the full article

Peter C. Albertsen

University of Connecticut Health Center, Farmington, CT, USA

References

1 Bill-Axelson A, Holmberg L, Garmo H et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 2014; 370: 932–42

2 Thompson IM, Tangen CM, Paradelo J et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer signiﬁcantly reduces the risk of metastases and improves survival: long-term followup of a randomized trial. J Urol 2009; 181: 956–62

3 Bolla M, van Poppel H, Collette L et al. Postoperative radiotherapy after radical prostatectomy: a randomized control trial (EORTC trial 22911). Lancet 2005; 366: 572–8

4 Wiegel T, Bottke D, Steiner U et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-speciﬁc antigen. ARO 96-02/AUO AP 09/95. J Clin Oncol 2009; 27: 2924–30

5 Hsu D, Paciorek A, Cooperberg M et al. Postoperative radiation therapy for patients at high risk of recurrence after radical prostatectomy: does timing matter? BJU Int 2015; 116: 713–20

Editorial: LUTS – an independent risk factor for CVD

November 11, 2015/by Michael Kirby

Russo et al. [1] have identified LUTS as an independent risk factor for cardiovascular disease (CVD). The more severe the LUTS the more the CVD risk increased. LUTS in men is caused by a group of disorders, e.g. the metabolic syndrome and central obesity, which have similar risk factors to those that cause CVD [2]. Furthermore, LUTS is associated with erectile dysfunction (ED), which is well established as being linked to silent or symptomatic CVD [3]. The question arises as to whether the age of the patient rather than the LUTS is the cause for the CVD, in other words, is the LUTS merely a bystander or coincidental problem?

The evidence, however, is accumulating that LUTS is independent of age and a risk factor for CVD [2]. A multi-disciplinary consensus looked at ED and LUTS emphasising the importance of co-diagnosis with awareness of cardiovascular risk factors being present in patients with LUTS, ED, or LUTS and ED, and reviewed the literature on the underlying pathophysiology [2].

The link between ED and LUTS was brought home by the Multinational Survey of the Aging Male (MSAM) study. Many large epidemiological studies using well-powered multivariate analyses consistently provide overwhelming evidence of a link between ED and LUTS [4].

The pathogenic mechanisms underlying the relationships between ED and LUTS have been the subject of several recent reviews [5]. The underlying mechanisms include: the alteration of the nitric oxide-cyclic guanosine monophosphate pathway, enhancement of Rho-kinase (ROCK) signalling, autonomic hyperactivity, and pelvic atherosclerosis, secondary to endothelial dysfunction [6]. Additional contributing factors may include chronic inflammation and sex steroid ratio imbalance, all of which contribute to increased CVD risk.

LUTS, with or without ED, should trigger a search for cardiovascular risk factors and metabolic problems. In 2008, the International Journal of Impotence Research published a symposium entitled ‘Cardiac Sexology: Can we save a patient’s life and his love life?’. The recognition that urologists have an important role in the early identification of cardiovascular risk should encourage urologists to work closely with cardiologists [3].

Certainly the degree of risk recorded by Russo et al. [1] is substantially greater than one would expect from age alone. Possible mechanisms include the co-existence of inflammatory activity manifest by a raised C-reactive protein (CRP), which is commonly found in association with more severe LUTS and in turn, increased CVD risk [7]. Similarly chronic sleep disturbance, especially nocturia, is common in both LUTS and CVD, as is depression [2].

Endothelial dysfunction, which is recognised to be the major vascular risk for CVD, also occurs in LUTS that is chronic or severe usually affecting the prostate gland or bladder. There are, therefore, strong links between LUTS, ED and CVD a common denominator being increased adrenergic tone. Patients with LUTS should be asked about alternative symptoms, including ED, and screened for cardiovascular risk even if they have no cardiac symptoms. LUTS may not be as strong a risk factor as ED for CVD, but it appears to be an independent marker for increased risk, which should not be ignored. Men are reluctant to volunteer their concerns, so it is important that healthcare professionals ask the appropriate questions.

Read the full article

Graham Jackson, Mike G. Kirby* and Ray Rosen†

St. Thomas’ Hospital, London, UK, *The Prostate Centre, London, UK and †New England Research Institutes, Inc. (NERI), Waterto wn, MA, USA

References

1 Russo GI, Castelli T, Privitera S et al. Increase of Framingham cardiovascular disease risk score is associated with severity of lower urinary tract symptoms. BJU Int 2015; 116:791–6

2 Kirby M, Chapple C, Jackson G et al. Erectile dysfunction and lower urinary tract symptoms: a consensus on the importance of co-diagnosis. Int J Clin Pract 2013; 67: 606–18

3 Nehra A, Jackson G, Miner M et al. The Princeton III consensus for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc 2012; 87: 766–78

4 Rosen R, Altwein J, Boyle P et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol 2003; 44: 637–49

5 Gacci M, Eardley I, Giuliano F et al. Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 2011; 60: 809–25

6 Kohler TS, McVary KT. The relationship between erectile dysfunction and lower urinary tract symptoms and the role of phosphodiesterase type 5 inhibitors. Eur Urol 2009; 55: 38–48

7 Vlachopoulos C, Ioakeimidis N, Stefanadis C. Biomarkers, erectiledysfunction, and cardiovascular risk prediction: the latest of an evolving concept. Asian J Androl 2015; 17: 17–20

Editorial: Is 42 days the ‘magic number’ for repeat TURBT?

November 4, 2015/by Eila Skinner

Gökçe et al. [1] have evaluated a group of 242 patients from 10 centres with high-risk non-muscle-invasive bladder cancer (NMIBC) who underwent repeat resection and subsequent follow-up treatment, including induction and maintenance BCG for at least 1 year. They included patients who had repeat transurethral resection (TUR) within 90 days and excluded anyone who was upstaged to T2 or who did not complete 1 year of maintenance BCG. They divided patients into two groups according to time to second TUR, Group A (14–42 days) and Group B (43–90 days). The groups were similar in terms of patient age and gender, tumour multifocality, presence of carcinoma in situ (CIS), and stage and grade. The only factors on multivariable analysis that were statistically significant predictors of recurrence were grade, associated CIS, and time to second TUR. Only grade and time to second TUR were significant predictors of progression.

Figures 1 and 2 in the paper show an enormous difference in both recurrence-free survival and progression-free survival according to time to second TUR. For both outcomes, 42 days seemed to be the ‘magic number’, since re-TUR after 42 days was associated with much worse outcome. Patients who had repeat TUR at >42 days had nearly double the rate of both recurrence and progression than those who had repeat TUR within 6 weeks.

This is quite a dramatic result, and it is hard to imagine biologically how such an effect could be explained. Second TUR has two primary objectives, to identify occult muscle-invasive disease, and to remove tumour that was inadvertently left behind at the first resection. Both of these goals have been shown to be important and to result in better outcomes compared with no repeat TUR [2]. However, in this study [1], patients who had repeat TUR at >6 weeks after the initial resection had a progression rate similar to those in prior studies who had no second TUR at all [2]. What could be occurring that would cause a delay of just a few weeks in second TUR to double the risk of subsequent progression of disease?

This is a retrospective study without centralised pathology review, and no information is available about the reasons that patients had repeat TUR at an earlier or later interval, nor about the pathological findings at the repeat TUR. One must be wary that there is significant selection bias involved. There is a hint of this in the fact that the rate of residual tumour at repeat TUR in the two groups is very different (35% vs 53%). Perhaps the later group also had a higher rate of residual invasive components on the repeat resection? Herr et al. [3] have shown that residual T1 disease on repeat TUR is highly predictive of subsequent progression. Or alternatively, perhaps it is the delay in administration of BCG that really results in the worse outcome? Patients with a longer delay to repeat TUR by definition also have at least an equivalent delay in starting BCG.

Although high-risk NMIBC can certainly be aggressive, it seems highly unlikely that a week or two-one way or another in terms of treatment would make such a huge difference in the outcome. However, this is a provocative study that remains to be validated. It will be useful to see if other groups with similar patient populations can duplicate these findings. For the time being, as a routine practice it makes sense to repeat the TUR sooner rather than later whenever possible.

Read the full article

Eila C. Skinner

Thomas A. Stamey Research Professor of Urology, Chair, Department of Urology, Stanford University, Stanford, CA, USA

References

1 Gokce MI, Baltaci S, Bozlu M et al. Signiﬁcance of the interval between ﬁrst and second transurethral resection on recurrence and progression rates in patients with high-risk non-muscle-invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin. BJU Int 2015; 116: 721–6

2 Divrik RT, Sahin AF, Yildirim U, Altok M, Zorlu F. Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate, and disease-speciﬁc survival: a prospective randomized clinical trial. Eur Urol 2010; 58: 185–90

3 Herr HW, Donat SM, Dalbagni G. Can restaging transurethral resection of T1 bladder cancer select patients for immediate cystectomy? J Urol 2007; 177: 75

Editorial: Post-prostatectomy incontinence in the irradiated patient: more than just a drop in the ocean

October 28, 2015/by admin Z.9

Improved early detection of prostate cancer has led to an increased incidence of this disease, and an increase in the number of patients undergoing radical prostatectomy (RP). The rate of post-prostatectomy incontinence (PPI) is difficult to determine because of the varying definitions of incontinence, but approximately one in five men require the use of pads in the long term after RP. Incontinence has a significant negative impact on quality of life, and remains many men’s greatest fear, especially for the one in four who present at the age of <65 years. While significant advancements have been made in prostate cancer treatment, strong evidence for the optimum management of PPI remains lacking. Most guidelines are based on grade B or C recommendation and many questions about its surgical management remain unanswered.

The artificial urinary sphincter (AUS) has stood the test of time and has long been considered the ‘gold standard’ treatment for PPI, especially for those with moderate to severe incontinence. The quoted success rates achieved with this device vary from study to study based on the varying definition of ‘dry’. The use of radiotherapy (RT) after prostatectomy is generally considered to have a negative impact on its efficacy and revision rate, although some data have been conflicting. In this month’s BJUI, Bates et al. [1] present a timely and well-structured systematic review and meta-analysis of AUS placement after RP and RT. By analysing pooled results, the authors set out to clarify the effect of RT on AUS efficacy and outcomes. In total, 1886 patients from 15 studies published between 1989 and 2014 were included in the meta-analysis, including 14 studies assessing surgical revision and 11 looking at persistent urinary incontinence. No randomized controlled trials were available for analysis. Retrospective reporting and a lack of standardized postoperative validated assessments were a weakness of individual studies, and efforts to limit the effects of study heterogeneity and risk of bias were made using statistical models. The revision rate after a mean follow-up of 38.4 months was significantly higher in irradiated vs. non-irradiated men (mean 37.3 vs 19.8%; P < 0.007); the risk ratio was 1.56 and number needed to harm was 4 (i.e. one surgical revision for every four AUS devices implanted in irradiated men). Infection/erosion and urethral atrophy accounted for approximately half and one-third of all revisions respectively. Persistent urinary incontinence was also more than twice as likely in irradiated vs non-irradiated men (29.5 vs 12.1%; P = 0.003; risk ratio 2.08, number needed to harm 9).

This study highlights the significant negative impact of RT after RP on functional outcomes and its treatment. This is particularly important considering that approximately one-third of patients will require adjuvant or salvage radiotherapy at some stage after RP. The development of incontinence after RT is primarily attributable to the negative effect of radiation on bladder and urethral tissue. Unlike outcomes with regard to erectile function, the type of primary surgery performed (open vs robotic) does not appear to have any significant impact on PPI [2]. Timing of RT also does not seem to affect function, with similar rates of incontinence reported for early (<6 months after RP) vs late (>6 months after RP) irradiation reported 3 years after RT (24.5 vs 23.3%, respectively; P = 0.79) [3].

New devices, such as the male sling, have increased the options for PPI treatment. Male slings have achieved popularity because of their safety, relative ease of insertion and patients’ strong desire to void naturally without fiddling with pumps. Kumar et al. [4] reported that one in four men who were recommended an AUS as the best option by their surgeon chose a sling; 92% who were offered either also opted against the gold standard AUS. Slings, however, have not fared well in patients with severe incontinence or those who have undergone RT. Pooled analysis of the AdVance^® sling reported ‘success’ rates of 56 and 54%, respectively, in these scenarios, compared with a mean overall ‘success’ rate of 75% [5]. Reported success, however, does not equate to being ‘dry’, as reported in many AUS studies, and this lack of uniformity in describing outcomes prevents adequate clarity when comparing different devices. Despite the lower success rate after RT, slings, unlike the AUS, do not appear to have any additional complications in this setting [1, 6], and sling failure does not appear to prejudice subsequent AUS placement [7].

To date, no randomized controlled trial has directly compared efficacy of the newer slings with the AUS. Well-designed trials, with standardized protocols and uniform long-term assessments of outcome, including complications and quality of life, are required to clarify their place in managing PPI. Current randomized controlled trials are evaluating these devices prospectively, and will provide much needed level 1 evidence in this field. The most interesting of these is the MASTER trial (Male synthetic sling vs Artificial urinary Sphincter Trial). This multicentre UK randomized controlled trial is for men with incontinence after prostate surgery for cancer or benign disease [8]. Patients of any age, with any level of incontinence are eligible, and previous RT is not an exclusion criterion. The trial aims to randomize 360 men and will also follow up 360 non-randomized men, and runs until 2019. This trial will help clarify the relative benefits of the devices by incontinence severity. It will also provide some prospective data on the effect of RT on outcomes, although the 2-year follow-up will be too short to evaluate this fully.

The question remains regarding which strategy is the best for post-prostatectomy irradiated patients. Until the results of good quality trials are available, the jury is out. The AUS remains the gold standard in this setting, for now. For patients with mild to moderate incontinence, the sling is an option, and offers some advantages, but offers a lower overall chance of becoming pad free. Patients must be carefully counselled about the risk/benefit of this approach compared with an AUS. Results of the MASTER trial will help better define management of this subgroup. For moderate to severe incontinence, the AUS is the gold standard, albeit with an increased risk of failure and revision. The present meta-analysis arms the clinician with much needed data to quantify the relative risk of complications and adverse outcomes in this setting, and will allow better counselling and management of patient’s expectations.

Read the full article

Majid Shabbir

Department of Urology, Guy’s Hospital, London, UK

References

1 Bates A, Martin R, Terry T. Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: a metaanalysis. BJU Int 2015; 116: 623–33

2 Haglind E, Carlsson S, Stranne J et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: a prospective, controlled, nonrandomised trial. Eur Urol 2015. doi: 10.1016/j.eururo. 2015.02.029. [Epub ahead of print]

3 Sowerby RJ, Gani J, Yim H. Long-term complications in men who have early or late radiotherapy after radical prostatectomy. Can Urol Assoc J 2014; 8: 253–8.

4 Kumar A, Litt ER, Ballert KN, Nitti VW. Artificial urinary sphincter versus male sling for post-prostatectomy incontinence-what do patients choose? J Urol 2009; 181: 1231–5.

5 Van Bruwaene S, Van der Aa F, De Ridder D. Review: the use of sling versus sphincter in post-prostatectomy urinary incontinence. BJU Int 2015; 116: 330–42

6 Zuckerman JM, Tisdale B, McCammon K. AdVance male sling in irradiated patients with stress urinary incontinence. Can J Urol 2011; 18: 6013–7.

7 Lentz AC, Peterson AC, Webster GD. Outcomes following artificial sphincter implantation after prior unsuccessful male sling. J Urol 2012; 187: 2149–53.

8 Abrams P. Male synthetic sling versus Artificial urinary Sphincter Trial for men with urodynamic stress incontinence after prostate surgery: Evaluation by Randomised controlled trial (MASTER), 2014. Available at: www.controlled-trials.com/ISRCTN49212975/MASTER. Accessed May 2015

Editorial: Is angiogenesis still an attractive target in metastatic castration-resistant prostate cancer?

October 21, 2015/by Joaquim Bellmunt

In this issue of BJU International, Karzai et al. [1] report the results of a phase I study of the anti-endoglin antibody TRC105 in patients with metastatic castration-resistant prostate cancer (mCRPC). This is a new anti-angiogenic compound with a unique mechanism of action.

Since the introduction of the concept of angiogenesis as a requirement for tumour growth and survival of solid cancers, a substantial body of research has emerged, establishing inhibition of angiogenic pathways as an important part of the armamentarium in several tumour types [2]. The idea of dynamic tumour angiogenic factors that are able to mediate neovascularisation has also been associated with tumour growth, progression and metastases in prostate cancer [1].

Some studies have revealed that microvessel density, a histological measurement of tumour angiogenesis assessed by immunohistochemical CD105 (endoglin), correlates with higher Gleason score and may predict disease progression, as well as poorer survival outcomes in patients with mCRPC. Accordingly, angiogenesis is considered an attractive target for therapeutic intervention in this disease and anti-angiogenic strategies have been studied in several clinical settings. Unfortunately, well established anti-angiogenic therapies have failed to improve survival outcomes in advanced prostate cancer. Bevacizumab or afilbercept, both combined with docetaxel, were evaluated in phase III clinical trials and no survival benefit was observed over docetaxel alone. Similarly, sunitinib was no better than placebo after chemotherapy treatment. Moreover, the recent COMET-1 trial failed to show survival benefit with cabozantinib, a dual vascular endothelial growth factor (VEGF) and MET inhibitor, in patients with mCRPC and, as a consequence, enrolment in other studies evaluating this agent has been discontinued. Strikingly, although no survival benefit has been reported, progression-free survival benefit has been observed in all of these trials.

Other anti-angionenic therapies have been investigated in patients with mCRPC. A phase II study combining thalidomide and bevacizumab with docetaxel plus prednisone showed that this is an active combination in this subset of patients. Unfortunately, the combination resulted in significant neurotoxicity and myelotoxicity, limiting its clinical use [3]. Lenalidomide was developed to have a more favourable toxicity profile compared with thalidomide and has shown activity as a single agent in patients with non-metastatic, biochemically-relapsed prostate cancer. Again, the large randomised phase III trial comparing docetaxel plus lenalidomide vs docetaxel plus placebo failed to show improvement in overall survival with the addition of this agent [4]. Finally, tasquinimod, another compound targeting angiogenesis, is under evaluation and the final results have not yet been reported. A phase III placebo-controlled study (NCT01234311), designed based on promising phase II data, is ongoing in men with mCRPC with bone metastases and is powered to detect an improvement in overall survival.

Overall, limited activity have been reported with the available agents and, until the results of the tasquinimod trial become available, additional investigations with better-targeted therapies and tools for patient selection are needed to define how this class of agents can improve survival outcome in mCRPC. In this setting, CD105 (endoglin), a homodimeric cell membrane glycoprotein that was initially identified as a human leukaemia-associated antigen, and later also found on endothelial cells, might serve as a reasonable reference point to continue research in this direction. CD105 is a TGFβ co-receptor that is essential for angiogenesis and is selectively expressed on proliferating endothelial cells of tumour vessels. All these properties make CD105 an attractive target for drug development, as targeting the vasculature of the tumour may be more effective than conventional anti-angiogenic therapy, such as anti-VEGF therapy [5].

TRC105, an antibody to CD105, caused a overall reduction in angiogenic biomarkers and reduced tumour burden in a phase I study of advanced solid tumours at doses that were well tolerated. Karzai et al. [1] report the results of a phase I study of TRC105 in patients with mCRPC. This study was designed to define the maximum tolerated dose and to access the safety and tumour activity of TRC105 in a small cohort of patients with mCRPC. Of note, given that TRC105 has a unique mechanism of action, the toxicity profile was not similar with those commonly associated with VEGF inhibition and, at 20 mg/kg, the drug was well tolerated. Although evaluating a small number of patients, the tumour activity of this agent seems to be similar to that of the other anti-angiogenic therapies, and the potential benefit will most likely be seen when combined with other therapies. In addition, exploratory analyses have identified changes in plasma VEGF and CD105 staining on endothelial cells of tumour vessels after treatment with TRC105. These findings suggest that higher levels of VEGF are a possible compensatory mechanism for TRC105-induced anti-angiogenic activity, providing a rationale for TRC105 combination with other anti-VEGF therapies.

It has been hypothesised that endoglin-expressing vessels resist treatment, with antibody targeting the VEGF receptor by allowing continued growth of human tumour xenografts. Therefore, combining anti-angiogenic strategies with agents having different mechanisms of action may be an option to overcome resistance and produce anti-tumour responses [6]. Results from the combination of TRC105 with axitinib in patients with metastatic RCC may support this concept and are now under evaluation (NCT01806064).

Over the last 5 years, treatment of mCRPC has evolved rapidly. Immunotherapy agents (sipuleucel-T), androgen inhibitors (abiraterone acetate and enzalutamide), radioisotope (Radium-223) and cytotoxic chemotherapy (cabazitaxel) have been shown to improve overall survival in randomised phase III clinical trials. However, despite these recent advances, disease progression remains a major cause of morbidity and mortality and new therapies or combinations are required to improve patient care offering them a higher chance of achieving long-term survival.

Anti-angiogenic agents are active in certain settings of prostate cancer and some significant responses have been reported. However, a deeper understanding of the biology of mCRPC is required to characterise the complex angiogenic pathways and to elucidate mechanisms of resistance to this class of agents. This, together with the development of biomarkers to predict responses to anti-angiogenic therapies, might assist in guiding novel treatment combinations and optimising clinical benefit based on patient selection.

Read the full article

Andre P. Fay*† and Joaquim Bellmunt*‡

*Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, †Faculdade de Medicina, Pontifıcia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil and ‡University Hospital del Mar, IMIM, Barcelona, Spain

References

1 Karzai FH, Apolo AB, Cao L et al. A phase I study of TRC105 anti-CD105 (endoglin) antibody in metastatic castration-resistant prostate cancer. BJU Int 2014; 116: 546–55

2 Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182–6

3 Ning YM, Gulley JL, Arlen PM et al. Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 2010; 28: 2070–6

4 Petrylak D, Fizazi K, Sternberg CN et al. A phase 3 study to evaluate the efﬁcacy and safety of docetaxel and prednisone with or without lenalidomide in patients with castrate-resistant prostate cancer (CRPC): the MAINSAIL trial. In 2012 ESMO Congress, Abstract LBA24, presented 30 September 2012

5 Horsman MR, Siemann DW. Pathophysiologic effects of vascular- targeting agents and the implications for combination with conventional therapies. Cancer Res 2006; 66: 11520–39

6 Gordon MS, Robert F, Matei D et al. An open label phase 1b dose escalation study of TRC105 (anti-endoglin antibody) with bevacizumab in patients with advanced cancer. Clin Cancer Res 2014; 20: 5918–26

Editorial: Chronic prostatitis – how to give our best without apposite vagueness

October 14, 2015/by Antonella Giannantoni

A patient with chronic prostatitis poses a significant challenge to the urologist in everyday practice. We are certain that all readers will be familiar with the effort required to manage a man with chronic prostatitis, not only in diagnostic and therapeutic interventions but also personal and psychological support. This is particularly true, when you consider that chronic prostatitis affects men of all ages and can significantly impair their quality of life and social functioning. Starting with medical considerations, the symptomatic, chronic forms of prostatitis, as defined by the USA National Institutes of Health (NIH) are chronic bacterial prostatitis (CBP; NIH category II) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS; NIH category III) [1]. These chronic conditions present with a wide range of clinical manifestations, but the four main primarily recognised symptoms are: urogenital pain, lower urinary tract symptoms (voiding or storage symptoms), alteration of the psychological status, and sexual dysfunction [2].

Prevalence rates are estimated at 2–10%, with some as high as 15–16% in Asian, European and North American samples [3]. Both CBP and CP/CPPS present with no one identified underlying cause, although infectious, genetic, anatomical, physiological, neurological, and immunological factors may be involved. For whatever reason, the underlying factor(s) of chronic prostatitis are likely to trigger tissue inflammation and immune responses which, in turn, induce bladder and pelvic pain leading to LUTS, ejaculatory pain, and pain in other regions, including the lower back and abdomen. The lack of a distinct aetiology has made making a specific diagnosis and effectively treating the disorder very arduous, presenting a serious challenge to urologists. In this respect, the difficulty for us is to do our best in trying to solve the problem, without apposite vagueness! [4]. In the obscurity of actual knowledge about the pathophysiology, diagnosis and treatment of CBP and CP/CPPS, it seems that recent insights can be favourably identified.

The consensus guideline on the diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome, published in BJUI by Rees et al. [5], indeed represents an important tool to provide guidance to urologists and healthcare professionals treating patients with CBP and CP/CPPS. Starting from a literature review of the most updated evidence-based information in the field of CBP and CP/CPPS, the consensus guideline provides new and useful recommendations in signs and symptoms evaluation, and clinical assessment and diagnosis of CBP and CP/CPPS. In this regard, reliable instruments, e.g. the NIH-Chronic Prostatitis Symptoms index (NIH-CPSI), IPSS and UPOINT (Urinary, Psychosocial, Organ-specific, Infection, Neurological/systemic, and Tenderness) scales [5], have been suggested to assess initial symptom severity, evaluate phenotypic differences, and monitor patients’ response to therapeutic intervention. In addition, psychological screening to evaluate the presence of psychological disorders, e.g. depression and anxiety, has been strongly recommended. What is most important is the detailed information about treatment approaches for each individual patient, according to history, physical examination, investigations, and stage of the disease. Specifically, levels of evidence and different recommendations are provided for α-blockers, antimicrobial therapy, phytotherapy, and pain management. This guideline also has the merit of being simple and easily understandable for non-specialists and patients in showing the most appropriate way in following a patient with CBP and CP/CPPS. We are sure that this consensus guideline represents a step forward to a more adequate approach in diagnosing and treating patients with chronic prostatitis. It can be a tool to improve awareness and recognition of these conditions, and for uniformity among different specialists involved in the field.

Read the full article

Antonella Giannantoni and Silvia Proietti*

Department of Surgical and Biomedical Sciences, Urolog y and Andrology Section, Ospedale S. Maria della Misericordia, University of Perugia, Perugia, and *Human itas Clinical and Research Centre, Department of Urology, Rozzano, Milan, Italy

References

1 Murphy AB, Macejko A, Taylor A, Nadler RB. Chronic prostatitis: management strategies. Drugs 2009; 69: 71–84

2 Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents 2008; 31 (Suppl. 1): S85–90

3 Habermacher GM, Chason JT, Schaeffer AJ. Prostatitis/chronic pelvic pain syndrome. Annu Rev Med 2006; 57: 195–206

4 Twain M. My Late Senatorial Secretaryship (written about 1867). In: Sketches New and Old. Hartford, CT, and Chicago, IL: The American Publishing Company, 1882. Available at: https://www.gutenberg.org/ﬁles/ 3189/old/orig3189-h/p3.htm. Accessed May 2015.

5 Rees J, Abrahams M, Doble A, Cooper A. Prostatitis Expert Reference Group (PERG). Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline. BJU Int 2015; 116: 509–25

Controversies in management of high-risk prostate and bladder cancer

October 12, 2015/by Stacy Loeb

Recently, there has been substantial progress in our understanding of many key issues in urological oncology, which is the focus of this month’s BJUI. One of the most substantial paradigm shifts over the past few years has been the increasing use of radical prostatectomy (RP) for high-risk prostate cancer and increasing use of active surveillance for low-risk disease [1,2].

Consistent with these trends, this month’s BJUI features several useful articles on the management of high-risk prostate cancer. The ﬁrst article by Abdollah et al. [3] reports on a large series of 810 men with D’Amico high-risk prostate cancer (PSA level >20 ng/mL, Gleason score 8–10, and/or clinical stage ≥T2c) undergoing robot-assisted RP (RARP). Despite high-risk characteristics preoperatively, 55% had specimen-conﬁned disease at RARP, which was associated with higher 8-year biochemical recurrence-free (72.7% vs 31.7%, P < 0.001) and prostate cancer-speciﬁc survival rates (100% vs 86.9%, P < 0.001). The authors therefore designed a nomogram to predict specimen-conﬁned disease at RARP for D’Amico high-risk prostate cancer. Using PSA level, clinical stage, maximum tumour percentage quartile, primary and secondary biopsy Gleason score, the nomogram had 76% predictive accuracy. Once externally validated, this could provide a useful tool for pre-treatment assessment of men with high-risk prostate cancer.

Another major controversy in prostate cancer management is the optimal timing of postoperative radiation therapy (RT) for patients with high-risk features at RP. In this month’s BJUI, Hsu et al. [4] compare the results of adjuvant (≤6 months after RP with an undetectable PSA level), early salvage (administered while PSA levels at ≤1 ng/mL) and late salvage RT (administered at PSA levels of >1 ng/mL) in 305 men with adverse RP pathology from the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. At 6.2 years median follow-up, late salvage RT was associated with signiﬁcantly higher rates of metastasis and/or prostate cancer-death. By contrast, there was no difference in prostate cancer mortality and/or metastasis between early salvage vs adjuvant RT. A recent study from the USA National Cancer Data Base reported infrequent and declining use of postoperative RT within 6 months for men with adverse RP pathology, from 9.1% in 2005 to 7.3% in 2011 [5]. As we await data from prospective studies comparing adjuvant vs early salvage RT, the results of Hsu et al. [4] are encouraging, suggesting similar disease-speciﬁc outcomes if salvage therapy is administered at PSA levels of <1 ng/mL.

Finally, this issue’s ‘Article of the Month’ by Baltaci et al. [6] examines the timing of second transurethral resection of the bladder (re-TURB) for high-risk non-muscle-invasive bladder cancer (NMIBC). The management ofbladder cancer at this stage is a key point to improve the overall survival of bladder cancer. Re-TURB is already recommended in the European Association of Urology guidelines [7], but it remains controversial as to whether all patients require re-TURB and what timing is optimal. The range of 2–6 weeks after primary TURB was established based on a randomised trial assessing the effect of re-TURB on recurrence in patients treated with intravesical chemotherapy [8], but it has not been subsequently tested in a randomised trial. Baltaci et al. [6], in a multi-institutional retrospective review of 242 patients, report that patients with high-risk NMIBC undergoing early re-TURB (14–42 days) have better recurrence-free survival vs later re-TURB (73.6% vs 46.2%, P < 0.01). Although prospective studies are warranted to conﬁrm their results, these novel data suggest that early re-TURB is signiﬁcantly associated with lower rates of recurrence and progression.

References

1 Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990–2013. JAMA 2015; 314: 80–2

2 Loeb S, Berglund A, Stattin P. Population based study of use and determinants of active surveillance and watchful waiting for low and intermediate risk prostate cancer. J Urol 2013; 190: 1742–9

3 Abdollah F, Klett DE, Sood A et al. Predicting pathological outcomes in patients undergoing robot-assisted radical prostatectomy for high- risk prostate cancer: a preoperative nomogram. BJU Int 2015; 116: 703–12

4 Hsu CC , Paciorek AT, Cooperberg MR, Roach M 3rd, Hsu IC, Carroll PR. Postoperative radiation therapy for patients at high-risk of recurrence after radical prostat ectomy: does timing matter? BJU Int 2015; 116: 713–20

5 Sineshaw HM, Gray PJ, Efstathiou JA, Jemal A. Declining use of radiotherapy for adverse features after radical prostatectomy: results from the National Cancer Data Base. Eur Urol 2015; [Epub ahead of print]. DOI: 10.1016/ j.eururo.2015.04.003

6 Baltacı S, Bozlu M, Yıldırım A et al. Signiﬁcance of the interval between ﬁrst and second transurethral resection on recurrence and progression rates in patients with high-ris k non-muscle-invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin. BJU Int 2015; 116: 721–6

7 Babjuk M, Bohle A, Burger M et al. European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer (Ta, T1, and CIS). Available at: https://uroweb.org/wp-content/uploads/EAU-Guidelines- Non-muscle-invasive-Bladder-Cancer-2015-v1.pdf. Accessed September 2015

8 Divrik RT, Yildirim U, Zorlu F, Ozen H. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial. J Urol 2006; 175: 1641–4

Stacy Loeb – Department of Urology, Population Health, and the Laura and Isaac Perlmutter Cancer Center, New York University, New York City, NY, USA

Maria J. Ribal – Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain

Editorial: Intralesional Collagenase injections in PD patients : do they IMPRESS and can we afford them?

October 7, 2015/by Tim Terry

The study by Lipshultz et al. [1] is a post hoc reworking of the results of the Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies (IMPRESS) I and II phase 3 trials (each included 418 randomised patients) of intralesional injections of collagenase clostridium histolyticum (CCH) in patients with Peyronie’s disease (PD). The intention being to identify specifically, which subgroups of patients with PD might do best with CCH treatment compared with their matched placebo controls, as determined by reductions in penile curvature deformity and Peyronie’s Disease Questionnaire (PDQ) PD Symptom Bother score at study week 52 compared with baseline.

In both IMPRESS studies, CCH-treated patients showed statistically greater mean improvements vs placebo for reduction of penile curvature and PDQ PD Symptom Bother score. The current authors [1] have reassessed these previous results using four patient cohort variables, namely, baseline penile curvature, duration of PD, degree of penile calcification, and baseline erectile function severity, which were then further divided using various descriptors.

The results show that intralesional CCH significantly reduced baseline penile curvature in both the 30–60 and 61–90° curvature cohorts (P < 0.001 and P <0.008, respectively). Additionally, significant penile curvature improvements occurred with intralesional CCH when PD duration was >2 to <4 years and >4 years (P < 0.001).

CCH treatment in patients with PD with no penile calcification show statistically significant improvements in reducing baseline penile curvature and PDQ PD Symptom Bother score but this was not seen for either the noncontiguous stippling or contiguous calcification patient subgroups. Significant improvements in penile curvature occurred with intralesional CCH in patients with PD with a baseline International Index of Erectile Function (IIEF) score of >17 (P < 0.001) and the PDQ PD Symptom Bother score was also significantly reduced in these patients. Although these results are statistically meaningful, the clinical benefits are less readily discernible considering 12.5° was the largest difference in the reduction of mean penile curvature in all subgroups when comparing intralesional CCH to placebo at week 52. Similarly, although statistically significant changes in the PDQ PD Symptom Bother score were reported for intralesional CCH for the subgroups with duration of disease of >4 years, no penile calcification, and IIEF of >17, it is unclear what clinical benefit would accrue with a maximal change of 1.4 in any of the randomised subgroups.

Importantly, the IMPRESS I and II studies were not designed for subgroup analysis and despite combining these studies some of the specified PD subgroups contained in the present paper contain too few subjects to allow a valid statistical analysis of CCH efficacy. This has prompted the authors to conclude that further adequately powered prospective, randomised studies should be conducted to further clarify which PD characteristics offer optimal patient benefit with CCH treatment. The outcomes of these future studies might then optimise healthcare expenditure for a non-surgical treatment (consisting of eight penile injections and modelling), which shows therapeutic promise for patients with PD but potentially has significant consumer cost issues, which may be prohibitive unless some clinician guidelines exist for the use of CCH treatment. This has relevance as the USA Food and Drug Administration has already approved the use of intralesional CCH for the treatment of adult men with PD, who at the start of therapy have a palpable plaque and a curvature deformity of ≥30° [2].

Importantly, the outcomes of the patients with PD in the IMPRESS studies were only reported to week 52 of the study, which begs the questions as to how long any clinical benefit might last in patients who initially respond to intralesional CCH and whether these patients once having relapsed might respond to adjuvant injections.

Read the full article

Tim Terry

Department Urology, Leicester General Hospital, Leicester

References

1 Lipshultz LI, Goldstein I, Seftel AD et al. Clinical efﬁcacy of collagenase clostridium histolyticum in the treatment of Peyronie’s disease by subgroups: results from two large, randomised, placebo-controlled, phase 3 studies. BJU Int 2015; 116: 650–56

2 Honig SC. Intralesional collagenase in the treatment of Peyronie’s disease. Ther Adv Urol 2014; 6: 47–53