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Article of the Week: Detection and oncological effect of CTC in patients with variant UCB histology treated with RC

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Every week the Editor-in-Chief selects an 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.

Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy

Armin Soave*, Sabine Riethdorf†, Roland Dahlem*, Sarah Minner‡, Lars Weisbach*, Oliver Engel*, Margit Fisch*, Klaus Pantel† and Michael Rink*

 

*Department of Urology, †Institute of Tumor Biology, and ‡Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

 

How to Cite

Soave, A., Riethdorf, S., Dahlem, R., Minner, S., Weisbach, L., Engel, O., Fisch, M., Pantel, K. and Rink, M. (2017), Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy. BJU International, 119: 854–861. doi: 10.1111/bju.13782

Abstract

Objectives

To investigate for the presence of circulating tumour cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes.

Patients and methods

We prospectively collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5 mL) were analysed for CTC using the CellSearch® system (Janssen, Raritan, NJ, USA).

aotw-results-4

Results

Variant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and non-squamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P < 0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence [hazard ratio (HR) 3.45; P < 0.001] and cancer-specific mortality (HR 2.62; P = 0.002).

Conclusion

CTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavourable influence of non-squamous cell-differentiated UCB on outcomes.

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Editorial: Biomarkers for UCPPS: is there light at the end of the tunnel?

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Management of urological disease begins with an accurate diagnosis. For this purpose, urologists have PSA and biopsy for prostate cancer, bacterial culture for UTI, CT scan for urolithiasis, cytology, cystoscopy and biopsies for bladder cancer, semen analysis for infertility and the list goes on. We have been able to use these accurate diagnostic markers to kill, maim, remove, fragment or burn our way to therapeutic success. Unfortunately, this has not been true in the case of urological chronic pelvic pain syndrome (UCPPS), where specific diagnoses and therapeutic strategies continue to elude us. Urologists managing patients with UCPPS need something concrete and quantifiable to move the field and improve patient care. A validated and reliable biomarker might fit the bill.

As Dagher et al. [1] clearly show in their study, this is not going to be as easy as we had hoped. The research group analysed urine samples for candidate biological markers from both patients with UCPPS and healthy controls recruited for the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. The National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) developed the MAPP Research Network to provide a comprehensive, multidisciplinary research approach for UCPPS [2, 3]. A major goal of this novel initiative is to better understand UCPPS pathophysiology allowing improved diagnoses and patient stratification that informs identification of therapeutic targets and ultimately improves clinical management.

In the present study, candidate biomarkers were initially selected based on their proposed involvement in underlying processes implicated in UCPPS. The authors showed marginal biomarker discrimination between patients with UCPPS and healthy control subjects. Furthermore, they observed provocative biomarker patterns correlating with pain and urinary symptom severity. None of these observations were conclusive enough, however, to allow a clinically applicable differentiation between patients with UCPPS and control subjects with no UCPPS symptoms. The patterns associated with pain and urinary severity were also not sufficiently robust to provide clinical direction. The underlying reason for these results is probably related to our recent understanding that UCPPS is not a clearly defined disease, but rather a complicated syndrome consisting of a confusing myriad of clinical conditions involving the bladder, prostate and/or pelvic floor and probably systemic contributions from other systems, including the nervous system. Indeed, the chronic pelvic pain and urinary symptoms appear as a result of interrelated, but variable, pathophysiology incorporating inflammatory, microbial, endocrine, neuromuscular, peripheral and CNS and even psychological pathways. The systemic characterization of UCPPS in the MAPP Network supports the idea that each patient with a UCPPS diagnosis represents an individual clinical picture and symptom profile. The promise of well-powered and carefully controlled biomarker research, such as described in the present study, will probably be realized when fully integrated into a systemic clinical profile using phenotypic insights (biological and symptom) still evolving from the MAPP Network and other studies. This is expected to yield a better understanding of specific mechanisms and symptom profiles operative in individual patients or patient subgroups. Identification of biomarker patterns that inform the clinical picture has the promise to allow us, in future, to make individualized diagnoses leading to individualized mechanistically (not only phenotypically) directed prognostic and therapeutic strategies. Success in such efforts will lead to UCPPS becoming less of a urological mystery. Then this enigmatic condition might join other urological diseases for which we have accurate diagnostic algorithms and successful therapeutic interventions.

The ongoing MAPP-2 Research Network’s Symptom Patterns Study is using state-of-the-art approaches to examine closely the interrelationships between the inflammatory, endocrine, microbial, neurological and psychological systems and how these interactions influence patients’ symptoms over a 2–3-year time period. This includes correlations with diverse biological markers over time. It is hoped that MAPP-2 will unravel the tangled web of these mechanistic pathways, allowing better diagnosis and ultimately, better therapy for our patients with UCPPS. That is our promise of the light at the end of a very long urological tunnel.

J. Curtis Nickel *†

 

*Queen’s University, Kingston, ON, Canada and †Urology, Canada Research Chair in Urologic Pain and Inflammation, Queen’s University, Kingston, ON, Canada
 
Read the full article

 

References

 

1 Dagher A, Curatolo A, Sachdev M et al. Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. BJU Int 2017; 120: 130–42

 

2 Clemens JQ, Mullins C, Kusek JW et al. The MAPP research network: a novel study of urologic chronic pelvic pain syndromes. BMC Urol 2014; 14: 57

 

3 Landis JR, Williams DA, Lucia MS et al. The MAPP research network: design,patient characterization and operations. BMC Urol 2014; 14: 58–75

 

Editorial: Detection and oncological effect of CTC in patients with variant UCB histology treated with RC

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I read this article from Hamburg-Eppendorf with great interest [1]. The treatment of invasive urothelial carcinoma has not significantly progressed in the last 30 years, with survivals currently that are little changed since the first introduction of multi-drug platinum-based chemotherapy in the 1980s. Moreover, the broad application of chemotherapy, whether it is in the preoperative or postoperative domains, is associated with significant morbidity in this generally elderly population. As 60–80% of patients are cured by surgery alone, the broad use of chemotherapy in any setting results in unnecessary morbidity and occasionally mortality in some patients unnecessarily. Multiple patients have a permanent reduction in renal function when platinum is used in this setting. The decision to treat preoperatively is limited by inaccurate clinical staging and in the postoperative setting may be compromised by slow or incomplete surgical recovery.

The measurement of preoperative circulating tumour cells (CTC) provides us with a rational approach to more accurately select patients for neoadjuvant chemotherapy and would seem according to this article to independently predict disease recurrence, even when considering aggressive variant histologies. Examining Figure 2, one finds that even with variant histology, 60% of patients will not recur after cystectomy if they are CTC negative. The differences are even more profound in pure urothelial carcinoma, where the presence of detectable CTC decreases survival by 50%. The authors are to be congratulated for providing us with a potential rational methodology to determine the benefit from neoadjuvant chemotherapy in patients with bladder cancer prior to cystectomy. Next we should await the analysis of clinical trials stratified by CTC status.

Read the full article
Michael O. Koch, Chairman and Professor of Urology

 

Indiana Cancer Pavilion, Indiana University School of Medicine, Indianapolis, IN, USA

 

Reference

 

1 Soave A, Riethdorf S, Dahlem R et al. Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy. BJU Int 2017; 119: 854–61

 

Article of the Week: Evaluation of Sig24, a 24-gene signature

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Every week the Editor-in-Chief selects an 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 discussing the paper.

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

Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality

Kathryn L. Pellegrini*†, Martin G. Sanda*†, Dattatraya Patil*†, Qi Long†‡§, Marıa Santiago-Jimenez, Mandeep Takhar, Nicholas Erho, Kasra Yousefi, Elai Davicioni, Eric A. Klein**, Robert B. Jenkins††, R. Jeffrey Karnes‡‡ and Carlos S. Moreno†§§§

 

*Department of Urology, Emory University School of Medicine, †Winship Cancer Institute, Atlanta, GA‡ Department of Biostatistics and Epidemiology and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, §Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA, GenomeDx Biosciences, Vancouver, BC, Canada, **Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, ††Department of Pathology and Laboratory Medicine, ‡‡Department of Urology, Mayo Clinic, Rochester, MN, and §§Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Read the full article

How to Cite

Pellegrini, K. L., Sanda, M. G., Patil, D., Long, Q., Santiago-Jiménez, M., Takhar, M., Erho, N., Yousefi, K., Davicioni, E., Klein, E. A., Jenkins, R. B., Karnes, R. J. and Moreno, C. S. (2017), Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality. BJU International, 119: 961–967. doi: 10.1111/bju.13779

Abstract

Objectives

To determine the prognostic potential of a 24-gene signature, Sig24, for identifying patients with prostate cancer who are at risk of developing metastases or of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP).

Patients and Methods

Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time-dependent c-index analysis, Cox proportional hazards regression and Kaplan–Meier survival analysis.

aotw-jun-3-results

Results

Higher Sig24 scores were significantly associated with higher pathological Gleason scores in all three cohorts. Analysis of the Mayo Clinic II cohort, which included time-to-event information, indicated that patients with high Sig24 scores also had a higher risk of developing metastasis (hazard ratio [HR] 3.78, 95% confidence interval [CI]: 1.96–7.29; P < 0.001) or of PCSM (HR 6.54, 95% CI: 2.16–19.83; P < 0.001).

Conclusions

The findings of the present study show the applicability of Sig24 for the prognosis of metastasis or PCSM after RP. Future studies investigating the combination of Sig24 with available prognostic tests may provide new approaches to improve risk stratification for patients with prostate cancer.

Read more articles of the week

Editorial: Predicting outcome: role of gene signatures

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Pathological assessments, such as Gleason grading, which is a strong clinical predictor of prostate cancer progression [1], have a role to play in predicting the outcome of a patient’s response to therapy. The addition of PSA and TNM staging are further used to inform appropriate treatment strategies in patients who are at low, intermediate and high risk of disease progression. Unfortunately, approximately 30% of men with intermediate-risk prostate cancer will fail to be cured by surgery or radiation therapy approaches. This is not surprising as primary prostate cancer represents a complex heterogeneous disease that is clearly not fully explained by the current clinical prognostic factors, and further molecular characterization is required. There is now significant emerging evidence that the molecular characterization of tumours is important to enable us to stratify prostate cancer patients by their response to primary therapy and to identify the next appropriate steps in their treatment pathway.

Long et al. [2] have identified gene signatures that can define different genomic subtypes of prostate cancer and are predictive of biochemical recurrence. Erho et al. [3] discovered and validated a 22-gene signature, which they termed a genomic classifier for the prediction of early metastasis after radical prostatectomy, while Penny et al. [4] have identified an mRNA expression signature of Gleason grade which is predictive of lethal prostate cancer.

Long et al. [2] identified a 24-gene signature, which they discovered through RNA sequencing analysis of 100 formalin-fixed paraffin-embedded prostatectomy samples. They went on to validate their findings in a publically available independent gene expression microarray dataset of 140 patients. This 24-gene signature forms the basis of the present study by Pellegrini et al. [5], who refer to this gene signature as Sig24. In their study, they firstly undertook to determine if Sig24 was associated with pathological Gleason score as a marker of tumour aggressiveness, and then if it had prognostic value for the identification of patients at risk of metastasis or prostate cancer-specific mortality after radical prostatectomy. The Gleason score association study was carried out using the data from three independent case–control sets, including 182 patients from the Cleveland Clinic and two cohorts (cohort I, n = 545; cohort II, n = 235) from the Mayo Clinic, for which gene expression analysis had previously been conducted by Genome Dx using the Affymetrix Human 1.0 ST Genechip platform. The Sig24 score was calculated for each patient and higher Gleason score was associated with significantly higher Sig24 scores. The association studies for metastatic disease and prostate cancer-specific mortality, however, were only carried out in the Mayo Clinic cohort II. For both clinical endpoints the Sig24 score combined with the clinical model outperformed the clinical model alone of PSA, Gleason score and tumour stage. For metastatic disease the area under the curve for the clinical model alone was 0.69 (0.62–0.77) compared with 0.73 (0.66–0.78) for the clinical model combined with Sig24. For the prostate cancer-specific mortality endpoint, the area under the curve for the clinical model alone was 0.69 (0.67–0.87) compared with 0.74 (0.63–0.85) for the clinical model combined with Sig24.

These gene signatures have significant potential for predicting the progression of disease rather than waiting for PSA relapse, which is currently used to identify disease recurrence, with interval to biochemical failure being the best univariate factor predicting prostate cancer mortality and overall survival [6]. This would allow the initiation of additional therapies before recurrence and a better outcome for the patient. This concept has been demonstrated in a study in which the use of the Decipher gene signature was shown to improve the identification of patients who could benefit from adjuvant radiotherapy and thus only these patients were targeted for therapy [7].

Incorporating these gene signatures in robust clinical assays and integrating them into clinical decision-making is the next essential step in order for these strategies to have an impact on patient outcomes.

Read the full article
Ronald W. Watson
UCD School of Medicine, University College Dublin, Dublin, Ireland

References

1 Gleason DF. Classification of prostatic carcinomas. Cancer Chemother
Rep 1966; 50: 125–8
2 Long Q, Xu J, Osunkoya AO et al. Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence. Cancer Res 2014; 74: 3228–37

 

3 Erho N, Crisan A, Vergara IA et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One 2013; 8: e66855

 

4 Penny KL, Sinnott JA, Fall K et al. mRNA expression signature of Gleason grade predicts lethal prostate cancer. J Clin Oncol 2011; 29:2391–6

 

5 Pellegrini K, Sanda MG, Patil D et al. Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality. BJU Int 2017; 119: 961–7

 

6 Buyyounouski MK, Pickles T, Kestin LL, Allison R, Williams SG. Validating the interval to biochemical failure for identification of potentially lethal prostate cancer. J Clin Oncol 2012; 30: 1857–63

 

7 Den RB, Yousefi K, Trabulsi EJ et al. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol 2015; 33: 944–51

 

Video: Evaluation of a 24-gene signature for prognosis of metastatic events and PCa-specific mortality

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Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality

Kathryn L. Pellegrini*†, Martin G. Sanda*†, Dattatraya Patil*†, Qi Long†‡§, Marıa Santiago-Jimenez, Mandeep Takhar, Nicholas Erho, Kasra Yousefi, Elai Davicioni, Eric A. Klein**, Robert B. Jenkins††, R. Jeffrey Karnes
‡‡ and Carlos S. Moreno†§§§

 

*Department of Urology, Emory University School of Medicine, †Winship Cancer Institute, Atlanta, GA‡ Department of Biostatistics and Epidemiology and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, §Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA, GenomeDx Biosciences, Vancouver, BC, Canada, **Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, ††Department of Pathology and Laboratory Medicine, ‡‡Department of Urology, Mayo Clinic, Rochester, MN, and §§Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Read the full article

How to Cite

Pellegrini, K. L., Sanda, M. G., Patil, D., Long, Q., Santiago-Jiménez, M., Takhar, M., Erho, N., Yousefi, K., Davicioni, E., Klein, E. A., Jenkins, R. B., Karnes, R. J. and Moreno, C. S. (2017), Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality. BJU International, 119: 961–967. doi: 10.1111/bju.13779

Abstract

Objectives

To determine the prognostic potential of a 24-gene signature, Sig24, for identifying patients with prostate cancer who are at risk of developing metastases or of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP).

Patients and Methods

Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time-dependent c-index analysis, Cox proportional hazards regression and Kaplan–Meier survival analysis.

aotw-jun-3-results

Results

Higher Sig24 scores were significantly associated with higher pathological Gleason scores in all three cohorts. Analysis of the Mayo Clinic II cohort, which included time-to-event information, indicated that patients with high Sig24 scores also had a higher risk of developing metastasis (hazard ratio [HR] 3.78, 95% confidence interval [CI]: 1.96–7.29; P < 0.001) or of PCSM (HR 6.54, 95% CI: 2.16–19.83; P < 0.001).

Conclusions

The findings of the present study show the applicability of Sig24 for the prognosis of metastasis or PCSM after RP. Future studies investigating the combination of Sig24 with available prognostic tests may provide new approaches to improve risk stratification for patients with prostate cancer.

Read more articles of the week

Article of the Week: Treatment of ED after RP using nerve grafts and end-to-side somatic-autonomic neurorraphy

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Every week the Editor-in-Chief selects an 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.

Long-term follow-up of treatment of erectile dysfunction after radical prostatectomy using nerve grafts and end-to-side somatic-autonomic neurorraphy: a new technique

Jose Carlos Souza Trindade*, Fausto Viterbo†, Andre Petean Trindade‡, Wagner Josen Favaro§ and Jose Carlos Souza Trindade-Filho*

 

*Department of Urology, † Divisions of Plastic Surgery,‡ Radiology, Botucatu School of Medicine, State University of Sao Paulo, Sao Paulo, and §Department of Anatomy, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil

 

Read the full article

Abstract

Objective

To study a novel penile re innervation technique using four sural nerve grafts and end-to-side neurorraphies connecting bilaterally the femoral nerve and the cavernous corpus and the femoral nerve and the dorsal penile nerves.

Patients and Methods

Ten patients (mean [± sd; range] age 60.3 [± 4.8; 54–68] years), who had undergone radical prostatectomy (RP) at least 2 years previously, underwent penile reinnervation in the present study. Four patients had undergone radiotherapy after RP. All patients reported satisfactory sexual activity prior to RP. The surgery involved bridging of the femoral nerve to the dorsal nerve of the penis and the inner part of the corpus cavernosum with sural nerve grafts and end-to-side neurorraphies. Patients were evaluated using the International Index of Erectile Function (IIEF) questionnaire and pharmaco-penile Doppler ultrasonography (PPDU) preoperatively and at 6, 12 and 18 months postoperatively, and using a Clinical Evolution of Erectile Function (CEEF) questionnaire, administered after 36 months.

Results

The IIEF scores showed improvements with regard to erectile dysfunction (ED), satisfaction with the VitalFlow and general satisfaction. Evaluation of PPDU velocities did not reveal any difference between the right and left sides or among the different time points. The introduction of nerve grafts neither caused fibrosis of the corpus cavernosum, nor reduced penile vascular flow. CEEF results showed that sexual intercourse began after a mean of 13.7 months with frequency of sexual intercourse varying from once daily to once monthly. Acute complications were minimal. The study was limited by the small number of cases.

Conclusions

A total of 60% of patients were able to achieve full penetration, on average, 13 months after reinnervation surgery. Patients previously submitted to radiotherapy had slower return of erectile function. We conclude that penile reinnervation surgery is a viable technique, with effective results, and could offer a new treatment method for ED after RP.

Read more articles of the week

Editorial: Somatic-autonomic neurorrhaphy for erectile function restoration after radical prostatectomy

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The authors of the present study [1] are to be commended for their efforts in describing their 3-year experience with a novel bilateral end-to-side somatic-autonomic neurorrhaphy intended to restore erectile function at least 24 months after radical prostatectomy, after which spontaneous return of erectile function is unlikely [2]. Using the principles of brain plasticity and neurotization, the authors describe, for the first time, bilateral sural neurografting between the femoral nerve and both the corpus cavernosum and the dorsal nerve of the penis to achieve penile re-innervation. The employed side-to-end neurorrhaphy theoretically limits functional damage during axonal sprouting, reinforces sensory–motor communications to the cavernous nerves, and promotes glans penis sensitivity, although direct evidence of these physiological and clinical outcomes is yet to be demonstrated. Furthermore, the authors astutely capitalize on the potential advantages of using a femoral donor nerve, including its proximity to the proximal penis, its diameter, the sufficient axon count, the mixed composition of sensory and motor fibres, and its secretion of acetylcholine which is an essential neurotransmitter in the nitric oxide-mediated pathway leading to penile tumescence.

What is especially singular about this technique is its application months after radical prostatectomy following demonstrated post-surgical loss of erectile function. Previous studies have focused on unilateral or bilateral sural [3-6] or genitofemoral [7] neurografting of the cavernous nerves at the time of radical prostatectomy before post-surgical loss of erectile function could be substantiated. Such studies have had mixed results, attributable in part to the success of the nerve-sparing radical prostatectomy technique in the hands of experienced high-volume surgeons [3, 6], and post-surgical exposure of the cavernous nerves to androgen deprivation or radiation therapy in some patients [3, 5]. Whereas post-radical prostatectomy re-innervation of the cavernous nerves may not be feasible or efficacious secondary to post-surgical and post-radiation fibrosis, the described technique does not require abdominopelvic access, is associated with a quick recovery time and minimal complications, and does not preclude subsequent penile prosthesis implantation if necessary.

The results of the present study show significant improvement in general sexual satisfaction from baseline to 6 months post intervention corresponding to achievement of flaccid erection for all patients; significant improvement in erectile dysfunction from baseline to 12 months post intervention corresponding to achievement of semi-rigid or rigid erections in 8/10 patients; and significant improvement in satisfaction with sexual intercourse from baseline to 18 months post intervention corresponding to achievement of penetration for 6/10 patients. It should be noted, however, that administration of the Clinical Evolution of Erectile Function instrument at 36 months postoperatively may have introduced recall bias in patient-reported erectile function. As would be expected, no significant differences were noted in sexual desire or orgasm satisfaction during the study period. These results were achieved without evidence of atrophy, fibrosis, or significant differences in vascular flow of the bilateral corpora cavernosa; and with minimal complications over the study period.

The present study provides preliminary data regarding the safety, feasibility and efficacy of bilateral sural neurografting between the femoral nerve and both the corpus cavernosum and the dorsal nerve of the penis to restore post-radical prostatectomy erectile function in a limited pool of 10 men. If these preliminary results are substantiated with long-term follow-up in a significant number of patients, it should prompt multi-institutional collaborations to appropriately power comparative effectiveness analyses of post-radical prostatectomy neurorrhaphy, such as the described technique to a regulatory-approved ethical sham intervention, vacuum assist device therapy, urethral suppository therapy, or intracavernosal injection therapy. Ideally, patients should be matched or statistical analyses should be controlled for patient age, relevant comorbidities, prostate cancer stage, pre-radical prostatectomy erectile function, nerve-sparing radical prostatectomy technique, androgen deprivation therapy, radiation therapy, response to phosphodiesterase-5 inhibition, and time interval between radical prostatectomy and intervention. Such multi-institutional studies would benefit from: standardized protocols for preoperative evaluation, operative technique, peri-operative care and post-surgical sexual stimulation; repeated-measure analyses of both objective assessments of the quality and duration of penile tumescence, as well as patient-reported outcomes of erectile function and disease-specific quality of life using validated instruments; report of oncological outcomes; and long-term follow-up. We would encourage the authors to produce a technical video demonstrating their technique so that it may be attempted and validated by other programmes. Urological surgeons with expertise in oncology, sexual function, and reconstruction may collaborate and pool patient data to achieve high-powered quality studies of novel techniques, such as the one described in the present study, for post-radical prostatectomy erectile function restoration.

Read the full article
Jaime A. Cavallo, and Ashutosh K. Tewari, Chairman
Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at M ount Sinai, New York, NY, USA

 

How to Cite

Cavallo, J. A. and Tewari, A. K. (2017), Somatic-autonomic neurorrhaphy for erectile function restoration after radical prostatectomy. BJU International, 119: 816–818. doi: 10.1111/bju.13858

References

1 Souza Trindade JC, Viterbo F, Petean Trindade A, Favaro WJ, Filho JC. Long-term follow-up for treatment of erectile dysfunction after radical prostatectomy using nerve grafts and end-to-side somatic-autonomic neurorrhaphy: a new technique. BJU Int 2017; 119: 948–54

 

2 Sridhar AN, Cathcart PJ, Yap T et al. Recovery of baseline erectile function in men following radical prostatectomy for high-risk prostate cancer: a prospective analysis using validated measures. J Sex Med 2016; 13: 435–43

 

3 Secin FP, Koppie TM, Scardino PT et al. Bilateral cavernous nerve interposition grafting during radical retropubic prostatectomy: Memorial Sloan-Kettering Cancer Center experience. J Urol 2007; 177: 664–8

 

4 Namiki S, Saito S, Nakagawa H, Sanada T, Yamada A, Arai Y. Impact of unilateral sural nerve graft on recovery of potency and continence following radical prostatectomy: 3-year longitudinal study. J Urol 2007; 178: 212–6

 

5 Hanson GR, Borden LS Jr, Backous DD, Bayles SW, Corman JM. Erectile function following unilateral cavernosal nerve replacement. Can J Urol 2008; 15: 3990–3

 

6 Davis JW, Chang DW, Chevray P et al. Randomized phase II trial evaluation of erectile function after attempted unilateral cavernous nerve- sparing retropubic radical prostatectomy with versus without unilateral sural nerve grafting for clinically localized prostate cancer. Eur Urol 2009; 55: 1135–43

 

7 Joffe R, Klotz LH. Results of unilateral genitofemoral nerve grafts with contralateral nerve sparing during radical prostatectomy. Urology 2007; 69: 1161–4

 

Article of the Month: GreenLight XPS for treating benign prostatic hyperplasia

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

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

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

GreenLight XPS for treating benign prostatic hyperplasia

Read the full article

This National Institute for Health and Care Excellence (NICE) guidance is the current, unaltered NICE guidance at time of publication. BJUI publishes selected NICE guidance relevant to urologists to extend their distribution and promote best practice.

 

 Recommendations

  • 1.1
    The case for adopting GreenLight XPS for treating benign prostatic hyperplasia is supported in non-high-risk patients. GreenLight XPS is at least as effective in these patients as transurethral resection of the prostate (TURP), but can more often be done as a day-case procedure, following appropriate service redesign.

 

  • 1.2

    There is currently insufficient high-quality, comparative evidence to support the routine adoption of GreenLight XPS in high-risk patients, that is those who:

    • have an increased risk of bleeding or
    • have prostates larger than 100 ml or
    • have urinary retention.

    NICE recommends that specialists collaborate in collecting and publishing data on the comparative effectiveness of GreenLight XPS for high-risk patients to supplement the currently limited published evidence.

 

  • 1.3
    Cost modelling indicates that in non-high-risk patients, cost savings with GreenLight XPS compared with TURP are determined by the proportion of procedures done as day cases. Assuming a day-case procedure rate of 36%, and that the GreenLight XPS console is provided at no cost to the hospital (based on a contracted commitment to fibre usage), the estimated cost saving is £60 per patient. NICE’s resource impact report estimates that the annual cost saving for the NHS in England is around £2.3 million. In a plausible scenario of 70% of treatments being done as day cases, the cost saving may be up to £3.2 million.

 

  • 1.4
    NICE recommends that hospitals adopting GreenLight XPS plan for service redesign to ensure that day-case treatment can be delivered appropriately.

 

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Editorial: Celebrating BAUS and NICE Guidance

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On behalf of the BAUS Council, I am delighted to write this editorial looking forward to the 73rd annual meeting of the BAUS, which will be held in Glasgow from 26 to 28 June. In response to feedback we had from delegates following BAUS 2016 and the successful European Association of Urology meeting in London this March, we have changed the format and duration of the meeting, ensuring that it has a distinct feel, reflecting the best of British Urology.

With Brexit looming and the precarious state of NHS finances, the continuing challenge for all of us working in the NHS is to deliver high-quality care within available resources, while embracing the latest evidence informing clinical practice. This month’s BJUI sees the first publication of National Institute for Health and Care Excellence (NICE) guidance on urological topics – ‘MTG29 GreenLight XPS for treating benign prostatic hyperplasia’ [1]. NICE has a fantastic track record in publishing highly regarded evidence-based syntheses across the breath of medicine and this guidance will stimulate the development and adoption of Greenlight laser for treating BPH as a day case procedure in the UK.

Assessing and critiquing new evidence are key elements of the annual BAUS meeting and this year is no exception. In all, 535 abstracts were submitted of which 157 will be presented. Whilst much of our clinical practice is of a high quality, analysis of the work done by the ‘Getting it right first time’ (GIRFT) team has shown a wide variation in practice for many common conditions in Urology. Simon Harrison, who leads the GIRFT team, will be giving an update on the progress of the work in a session looking at how standards can be applied in the real world at a session on Tuesday 27 June, entitled ‘Urology standards and the real world’.

On Monday 26 June, Academic Urology, Andrology and Genito-Urethral Surgery (AGUS), and Female, Neurological and Urodynamic Urology (FNUU) will be holding their annual meetings. State of the art lectures include Professor Trinity Bivalacqua speaking on ‘Molecular genetics and the prospect for future treatment strategies in Urology’. The AGUS section will focus on the genital emergencies consultation and the future of andrology in the UK, shedding light on specialist commissioning and training in the speciality. Highlights of the FNUU section meeting will include an update on meshes and tapes and the medicolegal consequences of adverse outcomes.

British urology has played a pivotal role in our understanding of the diagnosis and management of prostate cancer. Reflecting this, a point-counterpoint debate will take place on Tuesday 27 June, with Caroline Moore and Paul Cathcart debating the necessity for prostate biopsy in patients with Prostate Imaging Reporting and Data System (PI-RADS) 1and 2 lesions seen on MRI, drawing on evidence from the recent PROstate MRI Imaging Study (PROMIS) trial. On Wednesday 28, Noel Clarke will report on the latest news from the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) study, which to date has recruited >9000 patients. New evidence from the study is likely to herald a change in the care of our patients with metastatic prostate cancer.

In addition to state of the art papers, we are delighted to have a number of key opinion leaders attending the meeting. Reflecting the public’s high expectations and pressures on clinicians, Professor David Speigelhalter, Winton Professor for the Public Understanding of Risk at the University of Cambridge, will speak on the nature of risk and uncertainty in clinical practice. The BJUI Guest lecture will be delivered by David Prior (Parliamentary Under Secretary of State in the House of Lords). With the recent publication of The Long-term Sustainability of the NHS and Adult Social Care report [2], he is uniquely placed to give a perspective on the future direction of the NHS.

For the first time at our meeting there will be a session entitled ‘When things go wrong’. This session will focus on the impact of adverse events and burnout on Urologists, which promises to be insightful and thought provoking. With plenty of science, innovations in urological care and some politics, BAUS 2107 promises to be a fascinating meeting. I look forward to seeing you there.

Kieran O’Flynn

 

President of the BAUS

 

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How to Cite

O’Flynn, K. (2017), Celebrating BAUS and NICE Guidance. BJU International, 119: 815. doi: 10.1111/bju.13899

 

References

1 National Institute for Health and Care Excellence.MTG29 GreenLight XPS for treating benign prostatic hyperplasia.BJU Int 2017;119:823–30

 

2 House of Lords.The Long-term Sustainability of the NHS and Adult Social Care, 5 April 2017. Available at: https://www.publications.parliament.uk/pa/ld201617/ldselect/ldnhssus/151/151.pdf. Accessed 24 April 2017

 

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