Prostate cancer (PCa) is the second most commonly diagnosed cancer in the world. Primary treatment options include radiation therapy (external beam or brachytherapy) and radical prostatectomy (with or without pelvic lymph node dissection). The survival rate for men with prostate cancer is high and life expectancy after primary treatment is increasing. 

However, treatment of prostate cancer can be complicated by fistula formation of the urinary tract and/or osteomyelitis of the pubic symphysis. Little is known about the prevalence of this rare complication. After recovering from PCa, a fistula and/or osteomyelitis can have a significant negative impact on general health and quality of life. Symptoms of fistulation and/or osteomyelitis are recurrent urinary tract infections, urosepsis, transrectal fluid loss, urinary incontinence, chronic pain often increasing with mobilization. Conservative treatment consisting of urinary drainage (transurethral +/- upper tract drainage) and/or antibiotics is helpful in the short term for symptom improvement and infection control, but is rarely a long-term solution. A multidisciplinary surgical intervention comprising of symphysectomy and pubectomy, muscle flap and/or omentoplasty, and urinary reconstruction or cystectomy and urinary diversion is the only curative option. 

The past decade, a rapidly increasing number of patients with fistula and/or osteomyelitis after PCa treatment presented in our institution. In this study, we describe an overview of these patients and explore similarities in course of the disease.

All patients attending our tertiary referral center for a urological fistula after PCa treatment between 2014 and 2023 were included in this retrospective study. A distinction was made between a recto-vesical fistula (RVF), a urethro-cutaneous fistula (UCF) and a uro -symphyseal fistula (USF). Patient characteristics, primary, adjuvant and salvage PCa treatment and timings, and presenting symptoms were evaluated, as well as prior relevant medical history (endourological treatment of irradiated prostate or vesicourethral anastomosis stenosis (VUAS) specifically). The details (per- and perioperative) of the surgical treatment of urological fistula and/or osteomyelitis of the pubic symphysis were collected, including involved specialists, duration of surgery and length of stay.

Eighteen patients have been evaluated in our hospital with a urological fistula with or without osteomyelitis of the pubic symphysis after treatment for PCa (Table 1). Twelve patients (67%) were referred from another hospital. Patients presented with symptoms such as pain, significant loss of mobility, urinary incontinence, infections and urosepsis. There was one patient with a UCF, four with RVF and 13 with USF.

Figure 1 presents the disease course of the patients from PCa treatment to fistula development. Sixteen patients (89%) had prior radiotherapy (primary, adjuvant or salvage) and 11 patients (61%) underwent at least one endourological procedure. All patients who underwent an endourological procedure also had radiotherapy.
Focusing more specific on patients who developed a USF: 85% (11/13) had radiotherapy (primary or secondary) more than 5 years ago, 62% (8/13) of the patients received a endourological treatment after radiotherapy and 7 of those (88%) had ≥2 endourological procedures in the past.

Fifteen patients (83%) received treatment by a multidisciplinary team including specialists in infectious diseases, geriatrics, anesthesiology (including pain team), dietetics, physiotherapy and a surgical team consisting of urologists, orthopedic and plastic surgeons. Ten patients with a USF underwent a cyst(oprostat)ectomy with diversion, symphysectomy and pubectomy (N=9) and a rectus flap (N=8) or omentoplasty (N=1). The other three patients were either not fit for surgery, had no debilitating symptoms or are on the waiting list. Two patients with RVF received a fistula repair with omentoplasty, the other two a cystectomy or total exenteration with urinary diversion. 

The median length of hospital stay was 17 days (range 3 (robot assisted abdominal repair of RVF) – 41) and was longer than 14 days in 9/15 operated patients.

In this study we analyzed all patients diagnosed with a urological fistula with or without osteomyelitis of the pubic symphysis. A different course of the disease was found for fistula development after primary treatment of PCa between RVF’s and USF’s (figure 1). RVF’s developed immediately after primary treatment of PCa and USF’s after many years (mean 9 years, range 2-18). 

Different disease courses were also found between patients with USF. Patients who received primary or secondary radiotherapy in the distant past (first two groups presented in figure 1)  developed a USF very shortly after endourological treatment. We found that USF can also develop in patients with endourological treatment in the past and more recent radiotherapy. Finally, a group of patients developed a USF many years after secondary radiotherapy without prior endourological treatment. Nevertheless, it is remarkable that in most patients radiotherapy was many years ago and that most patients received multiple endourological treatments.  
 
As the USF developed very shortly after endourological treatment, we could conclude that one or more VUAS incisions/dilatations or incisions/resections of the necrotic prostate after radiotherapy trigger or induce the USF. Therefore, urologists should be aware of and patients should be counseled on the risk of developing a USF in patients with previous radiotherapy for PCa. We hypothesize that the risk on ventral perforation (USF development) in patients with a VUAS or radiated prostate is increased if a standard bladder neck incision (at 5, 7 or 12 o’clock) or a too rigorous dilatation is performed. Therefore we advise to perform an incision in the bladder neck more lateral (3 and 9 o’clock).

The occurrence of a urological fistula with or without osteomyelitis of the pubic symphysis is a severe and debilitating condition after treatment of PCa. Our cohort of patients with urological fistula after PCa treatment revealed that RVF often occurred shortly or immediately after PCa treatment, whereas USF was very late complication, often following endourological treatment in previously irradiated patients. Surgical treatment of urological fistula should be performed in a center of expertise by a multidisciplinary team, especially if coinciding with osteomyelitis of the pubic symphysis.