Tag Archive for: Article of the Week

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Video: Penile vibratory stimulation after radical prostatectomy

Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy: a randomized, controlled trial

Mikkel Fode*, Michael Borre, Dana A. Ohl, Jonas Lichtbach§ and Jens Sønksen*

*Department of Urology, Herlev University Hospital, Herlev, Department of Urology, Aarhus University Hospital, Aarhus, Denmark, Department of Urology, University of Michigan, Ann Arbor, MI, USA, and §Department of Physiotherapy, Herlev University Hospital, Herlev, Denmark

OBJECTIVE

• To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP).

PATIENTS AND METHODS

• The present study was conducted between July 2010 and March 2013 as a randomized prospective trial at two university hospitals. Eligible participants were continent men with an International Index of Erectile Function-5 (IIEF-5) score of at least 18, scheduled to undergo nerve-sparing RP.

• Patients were randomized to a PVS group or a control group. Patients in the PVS group were instructed in using a PVS device (FERTI CARE® vibrator).

• Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re-initiated for a period of 6 weeks.

• Participants were evaluated at 3, 6 and 12 months after surgery with the IIEF-5 questionnaire and questions regarding urinary bother. Patients using up to one pad daily for security reasons only were considered continent. The study was registered at https://clinicaltrials.gov/ (NCT01067261).

RESULTS

• Data from 68 patients were available for analyses (30 patients randomized to PVS and 38 patients randomized to the control group).

• The IIEF-5 score was highest in the PVS group at all time points after surgery with a median score of 18 vs 7.5 in the control group at 12 months (P = 0.09), but the difference only reached borderline significance.

• At 12 months, 16/30 (53%) patients in the PVS group had reached an IIEF-5 score of at least 18, while this was the case for 12/38 (32%) patients in the control group (P = 0.07).

• There were no significant differences in the proportions of continent patients between groups at 3, 6 or 12 months. At 12 months 90% of the PVS patients were continent, while 94.7% of the control patients were continent (P = 0.46).

CONCLUSION

• The present study did not document a significant effect of PVS. However, the method proved to be acceptable for most patients and there was a trend towards better erectile function with PVS. More studies are needed to explore this possible effect further.

 

Article of the week: Mirabegron is an effective treatment for OAB

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.

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

Phase III, randomised, double-blind, placebo-controlled study of the β3-adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder

Osamu Yamaguchi, Eiji Marui*, Hidehiro Kakizaki, Yukio Homma, Yasuhiko Igawa§, Masayuki Takeda, Osamu Nishizawa**, Momokazu Gotoh††, Masaki Yoshida‡‡, Osamu Yokoyama§§, Narihito Seki¶¶, Yasushi Ikeda*** and Sumito Ohkawa***

Division of Bioengineering and LUTD Research, School of Engineering, Nihon University, Koriyama, *Department of Human Arts Sciences, University and Graduate School of Human Arts Sciences, Saitama, Department of Urology, Asahikawa Medical University, Asahikawa, Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, §Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Department of Urology, University of Yamanashi, Yamanashi, **Department of Urology, Shinshu University, Matsumoto, ††Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, ‡‡Department of Urology, National Center for Geriatrics and Gerontology, Obu, §§Department of Urology, University of Fukui Faculty of Medical Sciences, Fukui, ¶¶Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, and ***Astellas Pharma Inc., Tokyo, Japan

Registered at clinicaltrials.gov (NCT00966004)

OBJECTIVE

• To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).

PATIENTS AND METHODS

• This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks.

• The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King’s Health Questionnaire.

• Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram.

RESULTS

• A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups.

• At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (–1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (–1.85 [2.555] vs –1.37 [3.191]; P = 0.025), incontinence episodes/24 h (–1.12 [1.475] vs –0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (–1.01 [1.338] vs –0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001).

• The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.

CONCLUSIONS

• Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

 

Editorial: Mirabegron the first β3-adrenoceptor agonist for OAB: a summary of the phase III studies

The study reported in this edition of BJUI details the results of a large phase III study conducted in Japan contrasting 50 mg mirabegron, the new β3-adrenoceptor agonist, to placebo with tolterodine as an active comparator [1]. This adds to the body of knowledge already provided by phase III evaluations reported from Europe [2], where tolterodine was also used as an active comparator and North America [3], where the efficacy of 25–100 mg was compared with placebo [4]. As the first in this new class of compounds with a mechanism of action that is distinct from that of the antimuscarinic agents, which are the mainstay of overactive bladder (OAB) therapy to date, there is clearly interest in the efficacy and in particular the safety of this new class of compound. This has been evaluated in a long-term safety study [5].

This paper [1] confirms the findings evident in these other publications, which suggest a favourable short- and long-term tolerability profile for mirabegron in patients with OAB. In particular, excluding typical anticholinergic side-effects, such as dry mouth, which occurred with a similar incidence with mirabegron as placebo, but was reported in 13.3% of tolterodine patients, there was no evidence of any cardiotoxicity with mirabegron, which is consistent with a previous pooled analysis of the European and North American studies [6]. In this pooled analysis, mirabegron was associated with mean increases of 0.4–0.6 mmHg in blood pressure and ≈1 beat/min in heart rate, both reversible upon treatment discontinuation. In the long-term study, the changes in heart rate seen with mirabegron 50 mg were less than those seen with tolterodine. Changes in vital signs did not result in more cardiovascular-related adverse events in patients treated with mirabegron compared with those treated with placebo or tolterodine in both the pooled 12-week and the 1-year long-term studies. In addition, there was one case of urinary retention with mirabegron in the pooled 12-week studies; the incidence being less than placebo or tolterodine. Clearly from the evidence now available, mirabegron has an efficacy similar to that seen with tolterodine and significantly better than placebo for most of the symptoms of the OAB symptom complex. In conclusion, mirabegron is well-tolerated and as efficacious as anticholinergic therapy. Further analyses of the phase III data has shown that mirabegron is effective in both naïve patients and those that have failed to either tolerate or respond to a previous anticholinergic therapy [7].

Future work should include an adequately powered direct comparison to antimuscarinic therapy. Furthermore, data on the combination of mirabegron and an antimuscarinic have already shown potential benefit in a phase II study, and this should be explored further [8]. Other interesting areas to explore will be the use of this therapy in both male patients and patients with neurogenic bladder dysfunction.

Christopher Chapple
Department of Urology, The Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK

 

References

  1. Yamaguchi O, Marui E, Kakizaki H et al. Phase III, randmised, double-blind, placebo-controlled study of the β3 -adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder. BJU Int 2014; 113: 951–960.
  2. Khullar V, Amarenco G, Angulo JC et al. Efficacy and tolerability of mirabegron, a β(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol 2013; 63: 283–295
  3. Nitti VW, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol 2013; 189: 1388–1395
  4. Herschorn S, Barkin J, Castro-Diaz D et al. A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder. Urology 2013; 82: 313–320
  5. Chapple CR, Kaplan SA, Mitcheson D et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder. Eur Urol 2013; 63: 296–305
  6. Nitti VW, Khullar V, van Kerrebroeck P et al. Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. Int J Clin Pract 2013; 67: 619–632
  7. Khullar V, Cambronero J, Angulo JC et al. Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial. BMC Urol 2013; 13: 45
  8. Abrams P, Kelleher C, Staskin D et al. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (symphony). Eur Urol 2014. doi: 10.1016/j.eururo.2014.02.012

 

Article of the week: Pilot study of EGFR-targeted therapies in men with penile SCC shows promising initial results

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. Pagliaro discussing his paper.

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

Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis

Bradley C. Carthon*§, Chaan S. Ng, Curtis A. Pettaway and Lance C. Pagliaro*

Departments of *Genitourinary Medical Oncology, Radiology, and Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
§
Current address: Winship Cancer Institute, Emory University,Atlanta, Georgia, USA

OBJECTIVE

• To evaluate the safety and efficacy of epidermal growth factor receptor (EGFR)-targeted therapy in patients with advanced penile or scrotal cancer.

PATIENTS AND METHODS

• We retrospectively reviewed the charts of patients with penile or scrotal squamous cell carcinoma who had visited our tertiary cancer centre between 2002 and 2009, including their subsequent treatment and follow-up.

• We collected details of EGFR-targeted therapy and clinical outcomes. Treatment-associated time-to-disease-progression (TTP), overall survival (OS), responses to therapy and toxicity were evaluate

RESULTS

• A total of 24 patients had received EGFR-targeted therapies, including cetuximab, erlotinib and gefitinib. The most common treatment given (to 67% of patients) was cetuximab combined with one or more cytotoxic drugs.

• The most common adverse effect was skin rash (71%). The median (range) TTP and OS were 11.3 (1–40) and 29.6 (2–205) weeks, respectively. The OS time for patients with visceral or bone metastases was significantly shorter than it was for those without (24.7 vs 49.9 weeks, P = 0.013).

• Among 17 patients treated with cetuximab alone or in combination with cisplatin, there were four partial responses (23.5%) including two patients with apparently chemotherapy-resistant tumours.

CONCLUSIONS

• Our results suggest that cetuximab has antitumour activity in metastatic penile cancer, and may enhance the effect of cisplatin-based chemotherapy.

• Prospective studies of EGFR-targeted therapies in men with these tumours are warranted

 

Editorial: Squamous cell carcinoma of the penis: therapeutic targeting of the EGFR

Squamous cell carcinoma of the penis is a rare genitourinary malignancy. There are wide variations in its incidence, ranging from 0.1 to 0.9/100 000 men in Europe, where it accounts for 1% of male malignancies, to as high as 4.4 and 4.2/100 000 men in Uganda and Paraguay, where it accounts for up to 10% of male malignancies.

The management of patients with advanced squamous cell carcinoma of the penis, including those patients with node-positive disease and metastatic disease, remains challenging. The beneficial effects of chemotherapy and radiotherapy are not established, partly because of the small numbers of patients within studies, but also because of the multiple regimens used for treatment, combined with relatively low response rates and high toxicities.

The presence and extent of lymph node metastasis is the single most common factor predictive of survival in men with penile carcinoma, with 5-year survival rates of 88% in men with minimal or no metastases (one to two nodes), compared with ∼25% in those men with two or more inguinal nodes involved. In men with extra nodal spread of the cancer and pelvic metastases, 5-year survival rates fall as low as 5–10%.

The most important aetiological factors for the development of squamous cell cancer of the penis appear to be the presence of a foreskin, immunosuppression and smoking. In addition to this, human papillomavirus (HPV) has been shown to have a central role in tumorogenesis [1]. HPV DNA can be identified in up to 80% of tumour specimens. The commonest subtypes expressed are the 16/18 subtypes (high risk) and the 6/11 subtypes (low risk). The virus exerts its tumorogenic effect via expression of viral oncogenes E6 and E7, which inhibit the activity of tumour suppressor genes p53 and RB. Whilst a number of potential biomarkers have been identified as prognostic indices of survival, translational research to date is limited [2].

A recent study from the UK has reported that survival rates in men with node-positive penile carcinoma have not improved significantly in the last 20 years [3]. In view of the poor response rates from chemotherapeutic agents, combined with their high toxicity and the poor survival rates in men with node-positive disease, it is imperative that more novel treatment methods, including targeted therapies, are developed to treat this devastating tumour.

A potential biological target in all squamous cell cancers, including the penis, is the epidermal growth factor family of receptors. A number of trials have been conducted to evaluate the safety profile and activity of a combination of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, including cetuximab, with schedules of platinum-based chemotherapy in a number of tumour sites. These combinations have shown good tolerability. The addition of cetuximab to platinum-based chemotherapy prolongs survival in patients with recurrent or metastatic squamous cell tumours of the head and neck.

Penile squamous cell tumours and their metastases also highly express EGFRs with ∼90 to 100% of tumours expressing the EGFR. The EGFR is a cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands. The EGFR is a member of the ErbB family of receptors, which consist of a sub-family of four closely related tyrosine kinases (EGFR [ErbB-1], HER2/c-neu [ErbB-2], Her 3 [ErbB-3] and Her 4 [ErbB-4]). EGFR can be activated by binding its specific ligands, including EGF and TGF-α. Dimerization of the EGFR stimulates tyrosine kinase activity and autophosphorylation of a number of tyrosine residues in the C-terminal domain of the EGF receptor, which downstream initiates a number of signal transduction cascades, ultimately resulting in cell migration and proliferation.

Cetuximab and panitumumab are monoclonal antibody inhibitors of the EGFR, which block the extracellular ligand-binding domains on the EGFR receptor. Furthermore, cetuximab induces the internalization of EGFR leading to downregulation of the EGFR. It also targets cytotoxic immune effector cells towards EGFR-expressing tumour cells (antibody-dependent cell-mediated cytotoxicity). Drugs, such as gefitinib are EGFR tyrosine kinase inhibitors, which bind and inhibit the EGFR tyrosine kinase by binding to the ATP-binding site of the enzyme. In lung tumours, patients who are EGFR-positive have shown relatively high response rates to tyrosine kinase inhibitors, although many patients develop resistance.

Two studies have analysed the expression of the EGFR receptor status in penile cancer [4, 5]. In both studies, the EGFR receptor was overexpressed in tumour tissue. In one study [4], 40 out of 44, i.e. 91% of patients, showed a positive EGFR expression in the primary tumour as well as in metastases. Importantly, a correlation between EGFR receptor expression and survival was not demonstrated.

In the present study by Carthon et al. [6], the authors evaluate the safety and efficacy of EGFR-targeted therapy using both cetuximab and tyrosine kinase inhibitors, including gefitinib. This pilot study evaluated 24 patients receiving EGFR-targeted therapies. Among 17 patients treated with cetuximab alone, or in combination with cisplatin, there were four partial responses. Whilst the presence of visceral metastases at the start of EGFR-based therapy was associated with poor time to progression and overall survival, several patients in that study were shown to have regression of predominantly inguinal and pelvic tumours. Interestingly, there were no objective responses to the small molecule inhibitors gefitinib or erlotinib. This pilot study would suggest that further prospective studies of EGFR-targeted therapies in men with squamous cell carcinoma of the penis are warranted and these initial results are promising; however, the number of regimens and agents used in the study is varied. This variation and the small number of patients and the retrospective nature of the study represent study limitations. Nevertheless, the concept of targeted therapies for squamous cell carcinoma of the penis should certainly be evaluated further, as it is clear that surgery alone is insufficient to improve survival in patients with N+ or M1 disease.

Suks Minhas
Department of Urology, University College Hospital, London, UK

  1. Minhas S, Manseck A, Watya S, Hegarty PK. Penile cancer. Prevention and premalignant conditions. Urology 2010; 76 (2 Suppl. 1): S24–35
  2. Kayes O, Ahmed HU, Arya M, Minhas S. Molecular and genetic pathways in penile cancer. Lancet Oncol 2007; 8: 420–429
  3. Kayes O, Freeman A, Lau D et al. Longitudinal analysis of outcomes for men with node positive penile cancer – are we improving? BJU Int 2013; 111 (S3): P19
  4. Börgermann C, Schmitz KJ, Sommer S, Rübben H, Krege S. Characterization of the EGF receptor status in penile cancer: retrospective analysis of the course of the disease in 45 patients. Urologe A 2009; 48: 1483–1489
  5. Lavens N, Gupta R, Wood LA. EGFR overexpression in squamous cell carcinoma of the penis. Curr Oncol 2010; 17: 4–6

Video: EGFR-targeted therapy in metastatic penile SCC

Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis

Bradley C. Carthon*§, Chaan S. Ng, Curtis A. Pettaway and Lance C. Pagliaro*

Departments of *Genitourinary Medical Oncology, Radiology, and Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
§
Current address: Winship Cancer Institute, Emory University,Atlanta, Georgia, USA

OBJECTIVE

• To evaluate the safety and efficacy of epidermal growth factor receptor (EGFR)-targeted therapy in patients with advanced penile or scrotal cancer.

PATIENTS AND METHODS

• We retrospectively reviewed the charts of patients with penile or scrotal squamous cell carcinoma who had visited our tertiary cancer centre between 2002 and 2009, including their subsequent treatment and follow-up.

• We collected details of EGFR-targeted therapy and clinical outcomes. Treatment-associated time-to-disease-progression (TTP), overall survival (OS), responses to therapy and toxicity were evaluate

RESULTS

• A total of 24 patients had received EGFR-targeted therapies, including cetuximab, erlotinib and gefitinib. The most common treatment given (to 67% of patients) was cetuximab combined with one or more cytotoxic drugs.

• The most common adverse effect was skin rash (71%). The median (range) TTP and OS were 11.3 (1–40) and 29.6 (2–205) weeks, respectively. The OS time for patients with visceral or bone metastases was significantly shorter than it was for those without (24.7 vs 49.9 weeks, P = 0.013).

• Among 17 patients treated with cetuximab alone or in combination with cisplatin, there were four partial responses (23.5%) including two patients with apparently chemotherapy-resistant tumours.

CONCLUSIONS

• Our results suggest that cetuximab has antitumour activity in metastatic penile cancer, and may enhance the effect of cisplatin-based chemotherapy.

• Prospective studies of EGFR-targeted therapies in men with these tumours are warranted

Article of the week: 1-week and 4-week stenting equally effective after pyeloplasty

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.

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

One- vs 4-week stent placement after laparoscopic and robot-assisted pyeloplasty: results of a prospective randomised single-centre study

H. Danuser, C. Germann, N. Pelzer, A. Rühle, P. Stucki and A. Mattei

Klinik für Urologie, Luzerner Kantonsspital, Lucerne, Switzerland

OBJECTIVES

To determine whether 1-week stenting of the pelvi-ureteric anastomosis of laparoscopic or robot-assisted pyeloplasty is as effective as 4-week stenting, based on their respective success rates.

PATIENTS AND METHODS

A total of 100 patients with pelvi-ureteric junction obstruction were treated by Anderson-Hynes pyeloplasty and the anastomosis was stented using a 6-F JJ catheter for either 1 week (1W series) or 4 weeks (4W series), based on a randomisation protocol. Postoperative follow-up was performed at 3 months using intravenous urography (IVU), at 6 months using diuretic renography and at 1, 3 and 5 years using ultrasonography. Statistical analysis was performed using a one-sided Z-test, Pearsons’s chi-squared test and a Wilcoxon rank sum test.

RESULTS

The primary outcome measure, success rate, which was defined as no obstruction on IVU and diuretic renography, was 100% in the 1W series and not inferior to the success rate of 98% in the 4W series (P = 0.006). The following secondary outcome measures were not significantly different between the 1W and the 4W series with regard to residual symptoms (10 vs 6%; P = 0.48), rate of complications (4 vs 6%; P = 0.65), need for synchronous robot-assisted pyelolithotomy (4 vs 8%; P = 0.47), improvement in split renal function (1 vs 0%; P = 0.59) and duration of surgery (200 vs 192 min; P = 0.87). Only length of hospital stay was significantly different; this was shorter in the 1W series (5 vs 6 days; P = 0.01).

CONCLUSIONS

Stenting of the pelvi-ureteric anastomosis after laparoscopic or robot-assisted pyeloplasty for 1 week is as effective as stenting for 4 weeks. Both procedures, laparoscopic or robot-assisted pyeloplasty have an excellent success rate.

Editorial: Early stent removal after pyeloplasty

In the current issue of BJUI Danuser et al. [1] present their prospective randomised single-centre study evaluating the effectiveness of 1-week vs the more traditional 4-week ureteric stent placement, after either a laparoscopic (LPP) or robot-assisted laparoscopic pyeloplasty procedure (RALPP) for PUJO.

In recent years LPP and RALPP have become the standard treatments for PUJO. In the adult population most patients undergoing this procedure require a period of ureteric stenting with a JJ stent, while the newly formed anastomosis heals. Many published pyeloplasty series report a stenting period of between 3 and 6 weeks [2-4]. The present study questions the need for such an extended period of stenting. With current minimal access techniques, either LPP or RALPP, it is possible to create a direct anastomosis between the ureter and renal pelvis similar to, and some would argue even more accurately than, that achievable via open surgery. The authors make the case that as historically most open pyeloplasty procedures were successfully stented for a period of 1 week, it seems only right to question why many of us continue to leave our ureteric stents in for longer periods after LPP and RALPP.

The negative impact of ureteric stent placement on patient health-related quality of life has been well documented in the literature. In 2003, Joshi et al. [5] published their study investigating the prevalence of symptoms associated with ureteric stents. They found that 78% of patients reported bothersome urinary symptoms that included storage symptoms, incontinence and haematuria, and >80% of patients had stent-related pain affecting daily activities. Furthermore, 58% reported reduced capacity to work and 32% reported sexual dysfunction. With this in mind, it is clear why we should try to reduce the period of ureteric stenting wherever possible, as long as it does not compromise patient outcome.

Danuser et al. [1] studied 100 consecutive patients with PUJO treated by an Anderson-Hynes pyeloplasty performed laparoscopically or robotically. Patients were randomly assigned to have a 6-F JJ catheter for either 1 week, or for 4 weeks. Their primary outcome, success rate (defined as no obstruction on the IVU or renogram), was 100% in the 1-week group and 98% in the 4-week group (P = 0.006), showing that 1 week is equally effective. For secondary outcomes measures they found no difference in residual symptoms, rate of complications, need for synchronous robot-assisted pyelolithotomy, improvement in split renal function and duration of surgery between the two groups. They therefore conclude that stenting of the PUJO anastomosis for 1 week after LPP or RALPP is as effective as stenting for 4 weeks.

We are all responsible for constantly evaluating and challenging our medical and surgical practice to ensure that we are providing the best care possible for our patients. In surgery, in the absence of high-level evidence, many of the decisions and actions we take are those inherited from our teachers and mentors, as practices that are thought to be safe and effective. Postoperative patient management is one area where clinicians vary greatly in their practice and we all strive to ensure a safe and comfortable recovery for patients, while not compromising on surgical outcome.

In the postoperative management of pyeloplasty patients many of us continue to leave ureteric stents in for up to 4–6 weeks, as this is ‘safe’ practice. It has been my observation that despite careful counselling of what patients should expect postoperatively when they have a ureteric stent in situ, many complain of stent symptoms and often seek medical advice. This prospective randomised single-centre study by Danuser et al. [1] provides us with good evidence to support the role for a shorter duration of stenting, particularly in this group of patients where a good anastomosis can be created, without compromising patient outcome.

Jane Letitia Boddy
Department of Urology, New Cross Hospitals NHS Trust, Wolverhampton, UK

References

  1. Chow K, Adeyoju AA, Section of Endourology of The British Association of Urological Surgeons. National practice and outcomes of laparoscopic pyeloplasty in the United Kingdom. J Endourol 2011; 25: 657–662
  2. Mufarrij PW, Woods M, Shah OD et al. Robotic dismembered pyeloplasty: a 6 year, multi-institutional experience. J Urol 2008; 180: 1391–1396
  3. Joshi HB, Stainthorpe A, MacDonagh RP, Keeley FX Jr, Timoney AG, Barry MJ. Indwelling ureteral stents: evaluation of symptoms, quality of life and utility. J Urol 2003; 169: 1065–1069

 

Article of the month: MRI and active surveillance for prostate cancer

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. Hyun M. Lee discussing his paper.

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

Role of multiparametric 3.0-Tesla magnetic resonance imaging in patients with prostate cancer eligible for active surveillance

Bong H. Park, Hwang G. Jeon, Seol H. Choo, Byong C. Jeong, Seong I. Seo, Seong S. Jeon, Han Y. Choi and Hyun M. Lee

Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Current address: Bong H. Park, Department of Urology, Incheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea

OBJECTIVE

• To evaluate predictors of more aggressive disease and the role of multiparametric 3.0-T magnetic resonance imaging (MRI) in selecting patients with prostate cancer for active surveillance (AS).

PATIENTS AND METHODS

• We retrospectively assessed 298 patients with prostate cancer who met the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, defined as T1c/T2, PSA level of ≤10 ng/mL, PSA density (PSAD) of <0.2 ng/mL2, Gleason score <7, and one or two positive biopsy cores.

• All patients underwent preoperative MRI, including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging, as well as radical prostatectomy (RP) between June 2005 and December 2011.

• Imaging results were correlated with pathological findings to evaluate the ability of MRI to select patients for AS.

RESULTS

• In 35 (11.7%) patients, no discrete cancer was visible on MRI, while in the remaining 263 (88.3%) patients, a discrete cancer was visible.

• Pathological examination of RP specimens resulted in upstaging (>T2) in 21 (7%) patients, upgrading (Gleason score >6) in 136 (45.6%), and a diagnosis of unfavourable disease in 142 (47.7%) patients.

• The 263 patients (88.3%) with visible cancer on imaging were more likely to have their cancer status upgraded (49.8% vs 14.3%) and be diagnosed with unfavourable disease (52.1% vs 14.3%) than the 35 patients (11.7%) with no cancer visible upon imaging, and these differences were statistically significant (P < 0.001 for all).

• A visible cancer lesion on MRI, PSAD, and patient age were found to be predictors of unfavourable disease in multivariate analysis.

CONCLUSION

• MRI can predict adverse pathological features and be used to assess the eligibility of patients with prostate cancer for AS.

 

Editorial: Multiparametric MRI and active surveillance for prostate cancer: future directions

A growing body of data exists suggesting an important role of MRI in selecting men with prostate cancer for active surveillance (AS). In the present study, Park et al. [1] show that a suspicious lesion on MRI was independently predictive of adverse pathology after radical prostatectomy (RP). This finding supports existing data suggesting that suspicious lesions on MRI confer an increased risk of disease reclassification among men enrolled in AS [2]. Indeed, in our institutional AS experience we found that men with a suspicious lesion on MRI were more likely to have biopsy reclassification with extended follow-up [3].While these data are provocative, much work remains to be done before the adoption of MRI as a standard screening tool for entry into AS for men with very low-risk prostate cancer.

Introduction of functional sequence imaging into multiparametric MRI protocols has resulted in improved detection and characterisation of clinically localised prostate cancer. However, before widespread implementation into AS protocols can occur, increased rigor and standardisation in image interpretation is needed. As in the present study, 5-point Likert scales have become an increasingly popular method of quantifying a lesions likelihood of representing cancer [1]. Still other authors have quantified a lesions level of suspicion using both weighted and non-weighted scoring systems based on the number of positive MRI sequences [3,4]. While useful for statistical analysis, these reporting methods are fraught with concerns of inter-observer variability and generalizability. Additionally, a recent report by Lee et al. [5] found that a simple measurement of lesion diameter on diffusion-weighted MRI was predictive of insignificant disease after RP. Combining the plethora of functional and morphological data obtained by multiparametric MRI into a standardised, reproducible tool will greatly facilitate implementation of MRI into current AS screening protocols.

As a step in the right direction, Stamatakis et al. [4] recently generated a nomogram for predicting biopsy reclassification in men on AS after taking into consideration both functional and morphological characteristics of MRI lesions. Adding an additional layer of complexity, they also assessed the utility of calculated values, e.g. lesion density (lesion volume/prostate volume), in predicting biopsy reclassification. Briefly, their analysis showed that the number of lesions, lesion suspicion, and lesion density were predictive of biopsy reclassification. While nomogram validation and testing of its predictive value on pathological outcomes is needed, this represents a major advance in the standardised application of MRI to AS cohorts.

Despite great strides in the application of multiparametric MRI to AS cohorts, a significant concern about the false-negative rate exists. Considering the present report, of the 35 men with no visible lesion on MRI, 14.3% men had unfavourable pathology after RP [1]. This is similar to previous studies reporting disease reclassification rates of <18% [2,6]. These men with normal imaging and high-grade cancer highlight the importance of incorporating imaging and clinical data when selecting men for AS. Better defining the false-negative rate of multiparametric MRI, and effectively identifying men with a normal MRI and high-grade disease remain major challenges.

Considering all of the available data, it is becoming increasingly clear that MRI has the potential for improving the identification of patients for whom AS would be safe. It is currently the practice at our institution to refer eligible men for multiparametric MRI before enrolment in AS. Our future scholarly efforts should be directed at the standardisation of reporting MRI data and the development of user-friendly AS criteria that synthesise MRI results with clinicopathological data.

Jeffrey K. Mullins and H. Ballentine Carter
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

References

  1. Park BH, Jeon HG, Choo SH et al. Role of multiparametric 3.0-Tesla magnetic resonance imaging in patients with prostate cancer eligible for active surveillance. BJU Int 2014; 113: 864–70
  2. Margel D, Yap SA, Lawrentschuk N et al. Impact of multiparametric endorectal coil prostate magnetic resonance imaging on disease reclassification among active surveillance candidates: a prospective cohort study. J Urol 2012; 187: 1247–52
  3. Mullins JK, Bonekamp D, Landis P et al. Multiparametric magnetic resonance imaging findings in men with low-risk prostate cancer followed using active surveillance. BJU Int 2013; 111: 1037–45
  4. Stamatakis L, Siddiqui MM, Nix JW et al. Accuracy of multiparametric magnetic resonance imaging in confirming eligibility for active surveillance for men with prostate cancer. Cancer 2013; 119: 3359–66
  5. Lee DH, Koo KC, Lee SH et al. Tumor lesion diameter on diffusion weighted magnetic resonance imaging could help predict insignificant prostate cancer in patients eligible for active surveillance: preliminary analysis. J Urol 2013; 190: 1213–7
  6. Guzzo TJ, Resnick MJ, Canter DJ et al. Endorectal T2-weighted MRI does not differentiate between favorable and adverse pathologic features in men with prostate cancer who would qualify for active surveillance. Urol Oncol 2012; 30: 301–5

 

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