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From the Desk of the Associate Editor: Prostate Cancer Radiation and Urethral Strictures: A Systematic Review and Meta-analysis

Urethral strictures do not tend to be at the forefront of most clinicians’ minds when considering the adverse effects of radiotherapy for prostate cancer. Quite correctly, the first considerations would be for those associated with any collateral damage to the rectum or bladder. But all urologists are well aware of radiation-related urethral strictures because the great majority would have these patients in their clinical workload. They are ‘heavy’ patients in that they need a lot of counseling and often require a lot of work to ‘manage’ their disease.  It is often a case of where a few patients as such can easily create an impression that their clinical workload for radiation-related urethral strictures is significant. 

Awad and colleagues (1) have performed a systematic review and meta-analysis specifically on the subject of urethral strictures developing after radiotherapy for prostate cancer and this work has recently been published on line ahead of print Prostate Cancer and Prostatic Diseases. Through a well-defined search strategy, 46 studies met the criteria for inclusion, representing a total of 16,129 patients. The median follow up time was relatively short at 4(interquartile range, IQR 2.7–5) years and where time to stricture formation was reported, the median time was 2.2 years (IQR 1.8–2.5, range 1.4–9). There was a pooled estimate period prevalence of 2.2% (95% confidence interval, CI 1.9–2.6%). If men were treated with both brachytherapy and external beam radiotherapy, this increased to 3% (95% CI 1–6%), supporting that dosimetry may have a contributing effect. These results are not dissimilar to recently published registry data which in effect confirms that urethral strictures following radiotherapy for prostate cancer occur sufficiently frequently to ensure that most urologists are going to be seeing these patients. 

This work is a natural progression from an increasing number of studies examining the adverse events observed following radiotherapy for prostate cancer.  In particular, the “Nam Trilogy” is a series of recently published manuscripts in high impact journals that have generated a great deal of discussion. The interest in these papers is reflected in their current Altmetric scores and citations of 34, 47, 150 and 112, 20 and 45 respectively. The first paper examined the incidence of complications other than urinary incontinence or erectile dysfunction following surgery or radiotherapy for prostate cancer and found a high rate of complications, particularly in those treated with radiotherapy (2). The second paper examined the overall rate of complications in men treated with surgery with or without subsequent radiation as well as those who received radiation alone. Men treated with radiation alone had the highest rates of complications (as measured by 5 year cumulative rates) followed by those having surgery and subsequent radiation and the least seen in those having surgery alone (2). The third paper examined the risk of second malignancies following radiotherapy for prostate cancer and small but measurable and potentially clinically significant increased risks were observed (3). 

Returning to the issue of urethral strictures, one unanswered question is the extent to which we could see more strictures over time.  The short median follow up identified in the Awad study may underestimate the true overall incidence of strictures.  Furthermore, none of the input studies in this review adequately address the impact of urethral stricture disease on quality of life and this obviously should be a target for future prospective studies. 

Written by:

Henry Woo, MD Associate Editor, Prostate Cancer and Prostatic Diseases Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney, Director of Uro-Oncology and Professor of Robotic Cancer Surgery at the Chris O'Brien LifeHouse cancer Hospital, Board Director of the Australian and New Zealand Urogenital and Prostate Cancer trials group (ANZUP) and a Board Director of the Australian Urological Foundation (AUF)

Read the PCAN Full-Text Article

References:

1. Awad MA et al.  Prostate cancer radiation and urethral strictures: a systematic review and meta-analysis.  Prostate Cancer and Prostatic Diseases 2018  doi:10.1038/s41391-017-0028-3
2. Nam R, et al.  Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study.  Lancet Oncol. 2014 Feb;15(2):223-31. doi: 10.1016/S1470-2045(13)70606-5. Epub 2014 Jan 17.
3. Wallis CJ et al. Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer.  Br J Cancer. 2015 Mar 17;112(6):977-82. doi: 10.1038/bjc.2015.54.
4. Wallis CJ et al.  Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis. BMJ. 2016 Mar 2;352:i851. doi: 10.1136/bmj.i851.