Can Reconstructive Urethral Surgery Proceed Without Randomised Controlled Trials?

Eur Urol 2008; 54: 709-711.

In the January 2008 issue, Richard Horton, editor of The Lancet, wrote that it is worth cheering for a different kind of scholarship in medicine [1]. He supports a new “old-fashioned scholarship” that transcends numbers and drives doctor–scholars into the polis of human health [1]. How should urologists deal with this opinion? What position should reconstructive urethral surgery take regarding this issue? The publication of a clinical trial marks the birth of new medical knowledge, and medical editors play the role of the midwife. For this reason, during the past two decades, randomised controlled trials (RCTs), under the most accurate statistical analysis, have become the best approach to answering medical questions, disseminating knowledge, and improving quality of care. They also have been instrumental in securing publication in major medical journals. As a result, modern medicine and, in general, medical science, seem to depend on a new number-based philosophy. If the power of the study cannot be measured by determining pre-enrolment sample size or α/β errors, or if the latest and most potent statistical tests have not been applied, it is commonly agreed that the research holds no validity. Doctors, health care payers, and patients increasingly have come to accept this authoritarian belief in numbers, making them the scholarly benchmark of our times. Within the urologic community, the use of nomograms, for example, recently has been introduced to predict outcomes for men with prostate cancer [2], [3]. These instruments allow urologists to go from “subjective” towards “objective” evaluation of patients and, as they are scientifically founded, should represent the most accurate model of a patient’s evaluation [4]. Guillonneau, however, reminds us that even if the previous statement on nomograms is correct, limiting factors exist as “nomograms imply a concept of stability: no change, no evolution, no modification, and no difference in surgery techniques and methods” [5].
Concurrently, public scepticism about timeliness, ability to perform studies skilfully without error, and honesty in reporting clinical trial results, has never been more pervasive. These issues continue to attract the attention of doctors, patients, media, and government organizations [6]. The result is a crisis of confidence in scientific publications. The response of the editor of European Urology, in line with editors of other medical journals of the International Committee of Medical Journal Editors (ICMJE), has been to promulgate strong positions on authorship and mandatory “full” registration of clinical trials in publicly funded, freely accessible registries [7], [8].
The question is: Can reconstructive urethral surgery escape this legacy? Recently, Dubey et al reported the results of RCTs on anterior urethroplasty comparing flaps to grafts [9]. This manuscript seems to fall under the category of modern medicine and good medical science and is in line with the scientific culture of our times. Unfortunately, when one reads the full article, one discovers that its practical and scientific values are debatable. The authors compare two different surgical techniques that have been used in two different conditions: penile and bulbar strictures. The authors failed to meet the standard of specific terminology, thus making it difficult to comprehend the full paper. They use the term “bulbopendulous strictures”; however, it does not emerge from the article if they are referring to a stricture located in the tract between the penile and bulbar urethra. Either it involves the overall anterior urethra length or it is a double stricture: one in the penile urethra and the other in the bulbar urethra. Only nine patients in this study actually had a penile urethral stricture, thus making it difficult to estimate statistical significance. This paper both reassures and discourages. It reassures because urologists involved in reconstructive urethral surgery seem to have achieved the highest standard of modern medicine with their results, but it discourages because patients, strictures, and techniques are not comparable due to the lack homogeneity. Being scientifically trained means we put our trust in numbers; however, we have our doubts that numbers, powerful and important as they are, should embody all the qualities of reconstructive urethral surgery.
What has history taught us? The history of urethral reconstruction is based on observational studies that appear today to be disarming in their apparent ease. In 1968, Orandi introduced the concept of penile skin flap urethroplasty, publishing a paper consisting merely of two pages and two black and white figures and that lacked any outcome assessment [10]. Oral mucosa has become the most popular substitute material in the treatment of urethral strictures, as it is readily available and easily harvested from the cheek, lip, or tongue, allowing for a concealed donor site scar and low oral morbidity [11], [12], [13], [14]. Unfortunately, all the papers that have contributed to the widespread use of the oral mucosa graft are retrospective, not prospective, and they are not RCTs. Urethral surgery for stricture repair is performed on a small sample size and, for this reason, the focus tends to be on the comparison of different techniques in homogeneous groups rather than prospective, randomised design studies. What does homogenous mean? It means that a technique used for penile urethra repair cannot be compared with a technique used for bulbar urethra repair. The skin flap technique presents surgical steps, a complication rate, and an outcome that is completely different if performed in the penile urethra or bulbar urethra. Selecting homogeneous groups means not enrolling patients with different urethral diseases. Urethroplasty presents steps, a complication rate, and an outcome that is completely different when performed for the treatment of strictures with different aetiologies such as trauma, lichen sclerosus, or failed hypospadias repair. Urologists commonly increase their sample size by combining patients with different strictures, different aetiologies, and different locations. Although this approach may allow the data to reach a significant power, it fails to provide homogeneous groups. In our opinion, reporting on a small group of homogeneous urethral conditions may provide more information and make a stronger “surgical” statement. Old urological scholarship considers the urethra as just a pipe through which urine passes, which is, of course, erroneous thinking! The urethra is more than just an anatomical entity; it is an organ involved in various functions and one that changes throughout development, aging, and pathologies. Anatomically, the urethra may be divided into three segments—penile, bulbar, and posterior—and each one has its anatomical, functional, pathological, and surgical framework. According to old urological scholarship, every narrow segment of the urethra is synonymous with stricture; again, this is incorrect! In our experience, we used the terms (1) “urethral stricture” for narrow segments that are not longer than 2cm, (2) “urethral stricture disease” for longer strictures, and (3) “pan-urethra stricture disease” when the stricture involves the anterior urethra in its entirety. Furthermore, patients with lichen sclerosus extending to the male genitalia and urethra suffer from a “complex immunological disorder, involving genital skin and urethra.” Finally, when we manage the patient with failed hypospadias repair, we refer to the condition as “complex congenital disease involving genitalia and urethra.” This terminology is not an exercise in philology, but instead has a patient-oriented prospective. We need to counsel patients and we need to be honest with them. Patients with a “urethra stricture” have a 90% success rate, which decreases to 80% in patients with “urethral stricture disease.” The success rate for patients with “complex immunological disorder, involving genital skin and urethra or congenital disease involving genitalia and urethra” does not exceed 70%, and 30% of these patients may require multiple, repeated surgeries to recover from urethra micturition [15]. As urologists involved in the study and treatment of urethral strictures, our challenge is to make room for a “new urethral science” that puts both learning and expertise scholarship to the best public use. We believe that this aspiration cannot be scientifically measured or appraised, as it is the essence of the fundamental fabric of the doctor’s purpose in reconstructive urethral surgery.Conflicts of interest: The authors have nothing to disclose.