Challenging RT complications require innovative strategies

Urinary complications following radiation therapy are increasing in prevalence, challenging to treat, and often require out-of-the-box surgical strategies. In this roundtable discussion, Urology Times Editorial Council member Bradley A. Erickson, MD, speaks with three expert reconstructive urologists-Benjamin N. Breyer, MD, MAS, Sean P. Elliott, MD, MS, and Jeremy B. Myers, MD-about their tips and tricks for managing these complications and their specific approach to three patient cases involving stricture and fistula.

Dr. Erickson:What types of complications from radiation therapy are you managing most often in your reconstructive practice?

Dr. Myers: Brad, thanks for bringing up this topic for discussion. Radiation complications are rarely talked about in the literature or at meetings, but the fact is that they can be absolutely devastating for patients and very challenging to manage. The typical patients we see in Utah are older men after the treatment of prostate cancer and women after the treatment of gynecologic malignancy. These patients have been cured of their disease, but in some cases, they are dealing with the long-term consequences of the treatment that are much worse than their initial cancer.

In Utah, once urologists realized we were willing to work with these patients, we started seeing an increase in the number of referrals for high-grade radiation complications. Those cases make up at least 25% of my current practice. Reconstructive urology is the ideal specialty to bring an “out-of-the-box” surgical strategy to these patients.

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We presented an algorithm for the workup of these patients recently in BJUI (2017; 119:700-8). The complications are so varied, and understanding which patients may benefit from lower urinary tract reconstruction versus those that need urinary diversion requires experience with the treatment of urethral and ureteral strictures, rectourethral fistula, and benign urinary diversion; ie, what works and what doesn’t.

Dr.Breyer: These are often very challenging cases, as the radiation has caused damage to the tissue that is irreversible. I’m always impressed by how surprised patients are when they present with a radiation complication, often believing it was a relatively “consequence-free” method of treatment. Erectile dysfunction is common, as is late-onset stress incontinence, which is likely the result of combined outlet dysfunction and bladder overactivity from radiation-induced ischemia.

Next: Are you seeing an increase in radiation induced urologic complications in your practice?

Dr. Erickson:Are you seeing an increase in radiation induced urologic complications in your practice?

Dr. Elliott: We looked at the incidence of radiation complications in the Medicare population and interestingly, at 5 years, radiation complications such as urethral stricture or radiation cystitis appeared to be less common than side effects from surgery-5% versus 10%. With surgery, you see all the side effects up front-in the first few months-whereas with radiation, they keep accumulating over the long term. By 10 years, however, the adverse effects started to become more common after radiation than after surgery (J Urol 2007; 178:529-34; Eur Urol 2015; 67:273-80).

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Dr. Breyer: It’s also important to consider that as time passes, even if incidence is stabilizing, the prevalence of radiation complications is always growing. Healing of radiation tissue is difficult to predict, and unlike many complications after surgery, radiation complications don’t lend themselves to simple solutions and often require repeated interventions for the rest of the patients’ lives.

Dr. Erickson:Radiation cystitis is the bane of many urologists’ existence, especially on an otherwise sleepy call weekend. Do you have any management tips or tricks for refractory radiation cystitis?

Dr. Myers: I am a firm believer in the use of hyperbaric oxygen for most radiation complications. The evidence for hyperbaric oxygen is the strongest for radiation cystitis. Large series of treatments have shown a durable short- and long-term success of 50%-80% for preventing recurrence of hematuria after treatment in both men and women after pelvic radiotherapy (Urology 2016; 94:42-6).

Hyperbaric appears to work best when it is given early after the onset of hematuria arising from radiation cystitis and in patients with lower radiation doses. Extrapolating from the data in radiation cystitis, I will also use hyperbaric oxygen treatment prior to performing most reconstructive surgeries in the setting of prior radiation. The concept is to improve tissue surrounding the worst of the radiation injury where the reconstruction is needed, so that postoperative healing is more successful.

Dr. Erickson:At what point is cystectomy the right option for radiation cystitis?

Dr. Elliott: There are the obvious situations, like hematuria with clot retention refractory to medical therapy, or urgency and frequency refractory to medical therapy. But often the driver is severe bladder pain, which is probably related to their small, contracted, spastic bladder that has become debilitating for the patient. Another indication is fistula to the pubic bone or the rectum. Some of these are correctable, but when the bladder is also small and contracted or when the findings are the results of combination radiation therapy such as brachytherapy plus external beam radiation, then I favor cystectomy.

Dr. Myers: When evaluating a patient for reconstructive surgery versus urinary diversion, the choice often comes down to the condition of the bladder. If the bladder has a capacity of less than 200 mL, the patient may heal very well with a “successful” reconstruction, but their quality of life is still very poor from urinary frequency and lack of adequate capacity.

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We recently published a case series looking at men undergoing cystectomy after experiencing complications from radiation therapy that was administered for the treatment of prostate cancer (World J Urol 2017; 35:1037-43). Despite being elderly, sometimes debilitated, and with a high number of comorbidities, the 90-day survival in these men was 95%. And once they make it through the sometimes difficult postoperative period, observing these patients’ progress is very gratifying. Most often, their pain is gone, they start to gain back weight, and they become re-engaged with their lives and families once they have recovered. They become a person again.

Next: Ureteral stricture in 35-year-old female

Dr. Erickson:How would you manage the ureteral stricture shown in figure 1? This is a 35-year-old female who developed a left ureteral stricture after radiation for cervical cancer that has failed conservative management with a ureteral stent.

Dr. Breyer: In addition to staging the level and extent of the ureteral injury, you’d want to stage her bladder. What are her voiding patterns like? Does she already suffer from overactivity? Some of our basic surgical tools need to be used with caution when radiation is involved. If the patient has a radiated, thickened, and dysfunctional bladder, then bladder flaps can be problematic. If there are concerns about voiding preoperatively, we would obtain urodynamics to document bladder function and size.

Figure 1. A 35-year-old female has a left ureteral stricture after radiation for cervical cancer that has failed conservative management with a ureteral stent. (Photo courtesy of Bradley A. Erickson, MD)

Dr. Elliott: This stricture appears relatively distal, so a psoas hitch may work. However, if the capacity is compromised and the stricture is high, I agree that bladder flaps can be problematic and I would go right to an intestinal interposition or even a nephrectomy. The bladder flap is not mobile, nor does it have reliable blood supply after radiation, making me worry about not only post-op bladder function but also a leak or stricture at the ureteroneocystostomy.

Next: Radiation-induced urethral anastomotic stricture in 65-year-old male

Dr. Erickson:How would you manage the radiation-induced urethral anastomotic stricture shown in figure 2? This is a 65-year-old male with a history of prostate cancer treated with IMRT who has failed urethral dilation and intermittent catheterization.

Dr. Elliott: Posterior urethroplasty is my preferred method of treatment, especially in patients who have failed standard endoscopic treatments. In patients with an intact prostate, salvage prostatectomy, either open or robotic, is an excellent option. The anastomosis can be difficult, but in our experience, is superior to any incisional method. In patients who have already undergone prostatectomy, the repairs can generally be performed perineally, although robotic bladder neck reconstruction is becoming more common and does offer the benefit of improved visualization for repairs that can traditionally require removal of pubic bone.

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Dr. Myers: Though I agree that posterior urethroplasty, with or without prostatectomy, is the best option, many patients don’t want another surgery, so we’ll manage them, at least initially, with endoscopic treatments.

I’m often asked about the use of mitomycin C. But in our retrospective data from the Trauma and Urologic Reconstruction Network of Surgeons (TURNS), mitomycin C did not seem to add much to the success of bladder neck incision and appeared to be locally very destructive in certain patients, especially after radiotherapy (J Urol 2015; 193:587-92). I believe, however, that if you choose to treat a bladder neck contracture with an incision, it is important to fully cut through the scar to where you start to see perivesical tissue and fat. I use a hot Collins knife as it helps with hemostatis and allows for a deeper cut.

Figure 2. Radiation-induced urethral anastomotic stricture in a 65-year-old male with a history of prostate cancer treated with IMRT who has failed urethral dilation and intermittent catheterization. (Photo courtesy of Bradley A. Erickson, MD)

It’s always necessary to prepare the patient for incontinence, and I present these strictures as a problem that requires a staged surgical approach: Stage 1, deep incision through the scar; and Stage 2, artificial urinary sphincter.

Dr. Erickson:Assuming the above patient will develop stress urinary incontinence after your procedure, would you manage the incontinence any differently than you would for the non-radiated patient?

Dr. Breyer: We’d wait a minimum of 3 months post-op before placing a urinary sphincter. In our experience, urethral slings seem to do poorly in the radiated population. In the preoperative visit, we will cystoscope the patient in the office to ensure the bladder neck contracture has stabilized. As long as the bladder neck is >14F, we’ll place the artificial urinary sphincter (AUS).

Dr. Elliott: I think this all comes down to setting proper (ie, low) patient expectations. This poor urethra has been radiated, and if you’ve managed the stricture with a urethroplasty, then it has been mobilized from its blood supply as well. So, I tell the patient up front that we are going to “up-size” the cuff to a looser fit and he should expect some mild incontinence afterward. When I explain that a little incontinence is better than the total incontinence he’ll have if (and when) he erodes with a cuff that is too tight, the men are very willing to accept the more conservative approach.

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Dr. Myers: Patency of the repair is key. In general, an AUS can be placed much more quickly after surgical reconstruction because the anastomosis is most often widely patent. After endoscopic management, however, the contracture continues to narrow with time, necessitating periodic cystoscopies and waiting a minimum of 3 to 6 months. Definitely, in complex cases, such as post urethroplasty or radiation, my choice is to place a transcorporal AUS cuff right from the start to decrease the risk of erosion. The TURNS group has shown this approach may provide some safety benefits, though erosions still occur (Urology 2014; 84:934-8).

Next: Rectourethral/rectovesical fistula in 58-year-old male

Dr. Erickson:How would you manage the rectourethral/rectovesical fistula shown in figure 3? This is a 58-year-old male who underwent adjuvant radiation therapy after a robotic prostatectomy and has failed a 3-month course of urethral catheterization. He is not fecally diverted.

Dr. Breyer: After radiated cases, we prefer to fecally divert the patient. In patients with completely devastated bladders and outlets in the setting of fistula, we will consider supravesical diversion. That said, most fistulas we encounter can be fixed by a prone perineal approach with interposition of gracilis muscle.

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If the hole is very large and the tissues are fixed, we will patch with a buccal graft and then parachute the muscle in. The muscle flap (sometimes bilateral) is critical here. Often there is necrotic and super-infected tissue that must be aggressively debrided and washed out to help prevent post-op infection/abscess.

Figure 3. Rectourethral/rectovesical fistula shown in a 58-year-old male who underwent adjuvant radiation therapy after a robotic prostatectomy and has failed a 3-month course of urethral catheterization. (Photo courtesy of Bradley A. Erickson, MD)

Dr. Elliott: Another option is a transabdominal rather than transperineal repair of the fistula. You can use the robotic approach for a re-do vesico-urethral anastomosis for bladder neck contracture too. You can use buccal graft and gracilis muscle, just like in the trasnperineal approach, or you can use omentum, but this approach isn’t for the faint of heart. The plane on the rectum is a tough one to find after radiation. However, as with the radiation cystitis case from above, if the bladder is poorly functioning, cystectomy is rarely the wrong answer if the patient is able and willing.

Dr. Erickson:Do you think more targeted, minimally invasive approaches to treating prostate cancer, such as cryotherapy and radioablative therapies, will decrease these types of complications?

Dr. Breyer: As imaging improves and as the therapies become more refined and directed, I have optimism that minimally invasive approaches will be an important part of the treatment algorithm for prostate cancer. At present, in my practice, while I currently don’t have a fair judgment of the denominator, there still seems to be a steady stream of complications from these minimally invasive treatments. Patients are always shocked when they develop a problem, as they are sometimes “sold” on the promise that the procedures are complication-free.

Dr. Elliott: I’ll play devil’s advocate here and say that at least RT has been around for decades and many of the kinks have been worked out. It has become more refined with treatments such as IMRT. In contrast, any new therapy, however minimally invasive or focal it is promised to be, can be expected to have some learning curve, which will always increase the risk of unexpected complications. In other words, I think there remains a future for reconstructionists.

Dr. Myers: One thing I feel strongly about is that we need to do a better job of predicting and defining the impact treatment complications have on patients to improve our pre-treatment counseling. As we’ve seen with radiation, and unlike surgery, complications can occur many years, even decades, after the treatment. I fear that these new treatments may be just delaying, but not preventing, complications.

We can only hope that wider adoption of active surveillance protocols will decrease the utilization of all unnecessary prostate cancer therapies. In the meantime, reconstructive urologists will continue to work on management strategies that minimize the impact that these complications have on our patients’ lives.

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