In 2016, the projected incidence of new cancer diagnoses in the United States was 1.68 million, with pelvic malignancies accounting for 19% of all cases. Prostate cancer accounted for 21.5% of all male malignancies and 61.9% of all male genitourinary malignancies last year. By 2024, the projected prevalence of prostate cancer survivors in the United States is 4.1 million. Prostate cancer treatments are variable. Although many therapies yield a high rate of cure, side effects such as urinary incontinence and sexual dysfunction are commonly seen.
An uncommon but significantly burdensome sequela of therapy for prostate cancer is pubic bone osteomyelitis in association with a pubosymphyseal urinary fistula. Due to improved awareness of the disease process underlying this condition, it has been increasingly reported as a side effect of ablative, surgical, and radiation treatments for prostate cancer. The presentation is variable, and includes difficulty with ambulation, chronic and unrelenting suprapubic pain, recurrent urinary tract infections, and urosepsis.[4,5] The diagnosis requires a high index of suspicion and should be followed by a thorough evaluation. Pubic bone osteomyelitis with an associated pubosymphyseal urinary fistula is a rarely reported pathology. However, case series in the medical literature reveal that the majority of patients had undergone some modality of radiation therapy (external beam radiotherapy or brachytherapy) as either monotherapy or salvage radiotherapy.[3,6-8] Endoscopic manipulation after treatment of prostate cancer has been suggested as a potential precipitating injury that leads to chronic extravasation of urine and subsequent fistulization and bone infection.[3,6]
Etiology and Pathogenesis
The etiology of pubic osteomyelitis secondary to a pubosymphyseal urinary fistula following therapy for prostate cancer is not well understood. However, multiple case series have attempted to better delineate the sequence of events that may account for development of this disease process. Prior to 2010, the majority of reports were limited to few patients. Between 2010 and 2016, three larger case series have been reported that have improved understanding of factors that may predispose certain patients to development of pubic osteomyelitis.
Matsushita et al reported on 12 patients with a history of prostate cancer, 4 of whom underwent a prostatectomy followed by salvage radiotherapy and 8 of whom underwent primary radiotherapy. All of these patients had a vesicourethral anastomosis stenosis or bladder neck contracture; and all were treated with an endoscopic procedure for management of the outlet prior to diagnosis of a pubosymphyseal urinary fistula. The median interval from endoscopic treatment to diagnosis was 36 months.
Gupta et al reported on 10 patients, 4 of whom were treated with prostatectomy followed by salvage radiotherapy, 5 of whom received radiotherapy (external beam and brachytherapy in 4 patients, and brachytherapy in 1 patient), and 1 of whom underwent high-intensity focused ultrasound. All of these patients subsequently had endoscopic procedures to manage bladder outlet obstruction. Lastly, Bugeja et al reported on 16 patients, 8 of whom had prostatectomy followed by radiation therapy, and 8 of whom received radiation therapy for prostate cancer. In this cohort, 15 of 16 patients had instrumentation of the urinary tract prior to diagnosis of a urinary fistula to the pubic symphysis.
The current literature supports that the combination of endoscopic management of bladder outlet obstruction in the setting of prior radiotherapy may be the inciting event for fistula formation in many of these patients. This then allows colonized urine to bathe the pubic symphysis, leading to infection. This infection can progress along the symphysis to the pubic bone and lead to chronic infection, bone necrosis, and formation of additional fistulae.
Patient Evaluation and Management
Given the paucity of data in the literature regarding this disease process, standardized guidelines have not been created. However, patients with the previously described constellation of signs and symptoms should undergo urine culture, measurement of white blood cell count with differential, a C-reactive protein test, and assessment of the erythrocyte sedimentation rate. Imaging is imperative for early and accurate diagnosis. Pelvic MRI is our preferred imaging modality for patient evaluation, given its ability to provide detailed information about bone cortical and medullary structure and integrity. MRI is the most sensitive and specific imaging method. On T1 imaging, there is decreased intensity of the bone marrow due to edema. On T2 imaging, the bone marrow is brighter than normal due to the existing edema. With the addition of gadolinium-based contrast agents, there can be enhancement of the areas of osteonecrosis, bone marrow, periosteum, or abscess margins (Figure 1).
Since these subtle changes in the bone can be missed by CT or imaging with plain film, it is preferable to use MRI for patient assessment to facilitate earlier recognition of bone disease. Additionally, soft tissue involvement and fistulous tracts are discernable with MRI. In patients who are unable to undergo MRI, plain film radiographs and CT scans of the pelvis often provide sufficient evidence to suggest the diagnosis. In our experience, patients with pubic bone osteomyelitis after treatment of prostate cancer also have an associated pubosymphyseal fistula to the urinary tract. The pelvic MRI or CT cystogram may delineate the fistulous connection, thereby confirming the diagnosis.
We have found that an aggressive multidisciplinary approach coordinated among clinicians from the urology, orthopedic surgery, and infectious diseases departments has been instrumental in the successful management of these patients. Referral to a tertiary center or an institution with expertise in this process is critical in maximizing patient outcomes. The reported rate of complications can be as high as 62.5%, with a hospitalization duration of up to 35 days in one series. The patient in whom pubic bone osteomyelitis in conjunction with a pubosymphyseal urinary fistula is suspected requires prompt evaluation of the entire genitourinary tract. The evaluation should include a voiding diary; pad weight testing if there is associated incontinence; abdominal and pelvic imaging to evaluate involvement of additional organs; cystoscopy to assess the bladder outlet and bladder; and, in selected cases, video urodynamic tests to evaluate detrusor function when planning for bladder preservation. Given the potential risk of secondary malignancies after certain prostate cancer treatment modalities, biopsies of the genitourinary tract may assist in guiding appropriate long-term care.
Patients frequently present after a protracted illness and are thus debilitated by significant pain and narcotic dependency. Therefore, prior to definitive therapy, nutritional and physical conditioning is required for healing. Empiric or culture-directed use of antibiotics in this preparatory period may prevent further deterioration of the patient’s health.
We have observed that some patients will present with repeated episodes of urosepsis in the absence of aggressive antibiotic therapy, which allows their deconditioned state to worsen. With management of the chronic infection to suppress acute flares, patients are then able to focus on nutritional optimization. Involving a nutritionist facilitates the identification of modifiable nutritional deficits. A subset of patients benefit from antibiotic treatment and subsequent antibiotic suppression. However, complete cure in these patients is not likely without surgical intervention. Signs and symptoms of the failure of conservative treatment include recurrent episodes of urosepsis despite antibiotic treatment or suppression; progressively worsening ambulation secondary to pain; suppurative eruptions of deep infections in the suprapubic area, thigh, and groin; and eruption of new fistulae. In this setting, the information gathered during the evaluation of the patient’s bladder allows for appropriate surgical planning.
The use of hyperbaric oxygen (HBO) therapy as adjunctive treatment in patients with bone osteomyelitis has been reported to be efficacious in multiple case series.[12-14] In our experience, early intervention using HBO treatment has not yielded any cases with resolution of pubic bone osteomyelitis or closure of the fistulous connection. Nevertheless, HBO therapy has been used with reproducible success in patients with poor wound healing, burn injuries, and radiation cystitis. Early HBO therapy, prior to surgical intervention, theoretically may afford the patient improved healing after surgical management of pubic bone osteomyelitis.
- Recurrent infections, bladder outlet obstruction, difficulty with ambulation, and suprapubic discomfort in patients with a history of prostatectomy and/or radiation therapy should raise suspicion for pubic osteomyelitis and urinary fistula.
- Endoscopic intervention for bladder outlet obstruction is frequently seen in pubic osteomyelitis with an associated urinary fistula.
- Pubic osteomyelitis with an associated pubosymphyseal urinary fistula is considered best managed by surgical intervention.
- In patients requiring urinary diversion, excision of the infected bone and fistulous connection is necessary to treat the underlying infectious process.
The cornerstone of success in management of the patient with pubic bone osteomyelitis with an associated pubosymphyseal fistula is resection of the infected bone, as well as resection of the fistulous tract, with or without urinary diversion (Figures 2 and 3). Determination of the best approach is driven by the bladder evaluation. Patients with a small fistulous defect, minimal bone disease, and a normal bladder may be considered candidates for reconstruction of the vesicourethral anastomosis, after debridement of the infected bone. In our experience, however, such reconstruction has not generally been possible; in most patients, the high degree of fistulization, extensive bone involvement, poor bladder capacity or compliance, and significant adherence of the bladder to the pubic bone makes salvage of the bladder a heroic measure that is likely to fail.
A history of radiation therapy as a salvage treatment or primary modality is frequently encountered in this patient group. The pelvic tissue quality is compromised as a result. In patients requiring a cystectomy, a simple cystectomy approach is preferred in order to avoid rectal or sigmoid injuries. We have typically avoided salvage prostatectomy in these patients and have no biochemical evidence of prostate cancer recurrence in our cohort. Reports in the contemporary literature on salvage prostatectomy for recurrent prostate cancer demonstrate a high rate of surgical complications, recurrent bladder neck contractures, and persistent incontinence.[15,16]
Performing a simple cystectomy at the time of urinary diversion has been demonstrated to add minimal blood loss and time to the operation. Given that the main drivers of illness are the pubosymphyseal fistula and associated infection, sparing the bladder and fistula by only creating a urinary diversion is not believed to constitute appropriate treatment. In a retrospective study on supravesical diversion with bladder retention over a 25-year period, 28% of the 35 patients who underwent this surgery had bladder-related complications.
The amount of bone resection required is determined by intraoperative findings. Although MRI is a very detailed imaging modality, the degree and extent of bone infection often cannot be appreciated on preoperative imaging. Indeed, friable and purulent bone are frequently encountered during surgery. Dissection proceeds until healthy bone is identified. This occasionally will require resection laterally in juxtaposition to insertion of the musculature of the lower limb (Figure 4). The bone is sent for culture to inform decision making regarding the postoperative antibiotic regimen. In collaboration with clinicians from the department of infectious diseases, treatment is initiated with either oral or intravenous alternatives to ensure adequate treatment of any residual infection.
Anecdotally, our patients do not appear to have worsening gait or pain as a result of the bone resection. In fact, we reported a significant decrease in perception of pain intensity in a cohort of 16 patients who had pubic bone osteomyelitis with an associated urinary fistula. Although infrequent, in some patients a rectourethral fistula may also be present. Because such patients have a more extensive field of injury, reconstructive alternatives are limited. We prefer a pelvic exenteration, performed in collaboration with colorectal surgeons, as a definitive treatment for these patients.
The postsurgical recovery period may be protracted. Hospitalization times range from 7 to 10 days, and 4 to 5 weeks in some series. Recent reports indicate very high complication rates associated with all types of cystectomy and urinary diversion, highlighting the complexity of patient management for this cohort.[21,22] Following surgery, patients may not be able to return to baseline activities for 1 to 3 months. We encourage our patients to engage in physical activity and maintain good nutritional habits after they have been discharged home. Postoperatively, we monitor patients for recurrent episodes of infection; changes in electrolyte and serum creatinine levels, and in the estimated glomerular filtration rate; evidence of obstruction on renal ultrasound; nutritional disturbances; serum B12 level; and gait instability.
Pubic bone osteomyelitis with an associated pubosymphyseal urinary tract fistula is an infrequently reported sequela of prostate cancer therapy. Diagnosis requires a high index of suspicion and appropriate workup. Although conservative therapies are appropriate, success is infrequent. Therefore, surgery is the recommended treatment approach for the definitive management of this disease process.
Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.
1. American Cancer Society. Cancer facts & figures 2016. Atlanta: American Cancer Society; 2016.
2. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252-71.
3. Gupta S, Peterson AC. Stress urinary incontinence in the prostate cancer survivor. Curr Opin Urol. 2014;24:395-400.
4. Ross JJ, Hu LT. Septic arthritis of the pubic symphysis: review of 100 cases. Medicine (Baltimore). 2003;82:340-5.
5. Alqahtani SM, Jiang F, Barimani B, Gdalevitch M. Symphysis pubis osteomyelitis with bilateral adductor muscles abscess. Case Rep Orthop. 2014;2014:982171.
6. Bugeja S, Andrich DE, Mundy AR. Fistulation into the pubic symphysis after treatment of prostate cancer: an important and surgically correctable complication. J Urol. 2016;195:391-8.
7. Lavien G, Zaid U, Peterson AC. Commentary on genitourinary cancer survivorship: physical activity and prostate cancer survivorship. Transl Androl Urol. 2016;5:613-5.
8. Matsushita K, Ginsburg L, Mian BM, et al. Pubovesical fistula: a rare complication after treatment of prostate cancer. Urology. 2012;80:446-51.
9. Gupta S, Zura RD, Hendershot EF, Peterson AC. Pubic symphysis osteomyelitis in the prostate cancer survivor: clinical presentation, evaluation, and management. Urology. 2015;85:684-90.
10. Bugeja S, Andrich DE, Mundy AR. Fistulation into the pubic symphysis after treatment of prostate cancer: an important and surgically correctable complication. J Urol. 2016;195:391-8.
11. Pineda C, Espinosa R, Pena A. Radiographic imaging in osteomyelitis: the role of plain radiography, computed tomography, ultrasonography, magnetic resonance imaging, and scintigraphy. Semin Plast Surg. 2009;23:80-9.
12. Chen CE, Ko JY, Fu TH, Wang CJ. Results of chronic osteomyelitis of the femur treated with hyperbaric oxygen: a preliminary report. Chang Gung Med J. 2004;27:91-7.
13. Yu WK, Chen YW, Shie HG, et al. Hyperbaric oxygen therapy as an adjunctive treatment for sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery. J Cardiothorac Surg. 2011;6:141.
14. Ahmed R, Severson MA, Traynelis VC. Role of hyperbaric oxygen therapy in the treatment of bacterial spinal osteomyelitis. J Neurosurg Spine. 2009;10:16-20.
15. Gotto GT, Yunis LH, Vora K, et al. Impact of prior prostate radiation on complications after radical prostatectomy. J Urol. 2010;184:136-42.
16. Ward JF, Sebo TJ, Blute ML, Zincke H. Salvage surgery for radiorecurrent prostate cancer: contemporary outcomes. J Urol. 2005;173:1156-60.
17. Rowley MW, Clemens JQ, Latini JM, Cameron AP. Simple cystectomy: outcomes of a new operative technique. Urology. 2011;78:942-5.
18. Adeyoju AB, Thornhill J, Lynch T, et al. The fate of the defunctioned bladder following supravesical urinary diversion. Br J Urol. 1996;78:80-3.
19. Becker I, Woodley SJ, Stringer MD. The adult human pubic symphysis: a systematic review. J Anat. 2010;217:475-87.
20. Lavien G, Chery G, Zaid UB, Peterson AC. Pubic bone resection provides objective pain control in the prostate cancer survivor with pubic bone osteomyelitis with an associated urinary tract to pubic symphysis fistula. Urology. 2016 Aug 31. [Epub ahead of print]
21. Al Hussein Al Awamlh B, Lee DJ, Nguyen DP, et al. Assessment of the quality-of-life and functional outcomes in patients undergoing cystectomy and urinary diversion for the management of radiation-induced refractory benign disease. Urology. 2015;85:394-400.
22. Osborn DJ, Dmochowski RR, Kaufman MR, et al. Cystectomy with urinary diversion for benign disease: indications and outcomes. Urology. 2014;83:1433-7.