Retroperitoneal fibrosis as a long-term complication of radiation treatment for prostate cancer.

To the Editor: A 70-year-old gentlemen presented with a six week history of abdominal pain associated with generalized weakness and anorexia. The patient reported insidious onset, 5 to 6/10 aching, and mid-abdominal pain which was aggravated in the supine position with no relation to food. Past medical history included a 30-pack year history of smoking and heavy alcohol consumption. Careful questioning revealed that six years prior, the patient had completed eight weeks of radiotherapy for carcinoma of the prostate. Physical examination revealed poorly localized lower quadrant abdominal tenderness, but there were no masses or organomegaly.

Laboratory workup was significant for blood urea nitrogen (BUN) of 35 and serum creatinine of 2.7. Ultrasound of the abdomen was followed by computed tomography (CT) scan without contrast of the abdomen, which revealed bilateral hydronephrosis and an ill-defined soft tissue mass surrounding the distal abdominal aorta mimicking a leaking aortic aneurysm (Fig. top panel). Cystoscopy showed evidence of diffuse fibrosis involving the posterior urethra and bladder, suggestive of secondary changes from radiation treatment. Retrograde pyelogram demonstrated bilateral hydroureteronephrosis and bilateral extrinsic ureteral compression with medial deviation. With difficulty, bilateral ureteric stents were placed over a guide wire through extremely small ureteral orifices.

The patients BUN and serum creatinine returned to baseline after stent placement. Subsequently, biopsy of the retroperitoneal mass was obtained though exploratory laparotomy. Pathology results from the biopsy specimens revealed chronic inflammatory cell infiltrates admixed with plasma cells, histiocytes and eosinophils, confirming the diagnosis of retroperitoneal fibrosis (RPF) (Fig. bottom panel).

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RPF is a rare entity with incidence varying from 1:200,000 to 1:500,000. (1) Although two thirds of these cases are idiopathic, it has been reported as a sequel of pelvic irradiation delivered for the treatment for testicular seminoma, colon carcinoma, pancreatic carcinoma, cervical carcinoma and uterine fibroma. (1-3)

Prostate cancer is the most common malignancy of men in the United States. External beam radiotherapy is the curative treatment for localized carcinoma of the prostate and has an important role in the adjuvant therapy for advanced cases. (4) In the patient reported here, prostate carcinoma was classified as localized adenocarcinoma of the prostate on histopathology and was clinical stage T1c with a Gleason score 2+3. Baseline prostate specific antigen (PSA) level was 5.7 ng/mL. Patient received 3 D conformal external beam pelvic radiotherapy. Total cumulative dose of 75.6 Gy radiations was delivered to the prostate in forty-two fractions over a span of eight weeks. Definitive remission was documented (PSA level less than 0.1) in subsequent follow-up visits. Patient seemed to be fine until he presented with acute renal failure and bilateral hydronephrosis and was found to have retroperitoneal fibrosis. To the best of our knowledge, only one case of localized fibrosis has been described in a patient receiving radiotherapy for prostate carcinoma. (5) In that case, the patient underwent transurethral resection of the prostate (TURP) for stage C adenocarcinoma of the prostate and postoperatively received 6000 rads of cobalt radiotherapy. One year later, he was found to have localized fibrosis involving urethras. In our case, the patient had rather extensive fibrosis involving multiple abdominal and pelvic viscera. Moreover, recognition of RPF as a sequel of radiotherapy for prostate carcinoma after such a long interval (six years in our case) is the first one of its kind.

RPF is characterized by dense fibrous plaque formation in the retroperitoneal structures. The hallmark of RPF is fibrosis and can involve the lower third of the ureters leading to obstructive uropathy as seen in our patient. Although poorly localized back pain is the most common presenting complaint, RPF may present with many other nonspecific symptoms, including anorexia, weight loss, anemia, mild fever or malaise. On account of these, the diagnosis is usually late. (1) As evident in our case, radiological evidence of RPF on IV urography includes a classic triad of upper ureteral hydronephrosis, medial deviation of the ureters and extrinsic ureteral compression. (1) CT and MRI are the modalities of choice for documenting the extent of disease. Medical management of RPF includes corticosteroid as first line and immunosuppressive drugs as second line drugs. Surgical options include relieving ureteral obstruction through surgical laparotomy or laparoscopic means. (1) The long term prognosis is usually favorable, but severe complications such as chronic renal failure, requiring renal replacement therapy, may arise. (1)

Our case documents that retroperitoneal fibrosis can arise as a sequel of radiation treatment for prostate cancer; therefore, we recommend prolonged follow-up of several years. We urge the target audience to identify this unusual but manageable complication of prostate cancer radiotherapy.

Ranjeeta Mani, MD*

Ashutosh Niraj, MD, MS[dagger]

Radhika Sreedhar, MD, MS*

From the *Department of Internal Medicine, Westlake Hospital, Melrose Park, Illinois; and the [dagger]Department of Internal Medicine, Wayne State University, Detroit, Michigan.

References

1. Vaglio A, Salvarani C, Buzio C. Retroperitoneal fibrosis. Lancet 2006;367:241-251.

2. Shental JS, Sudarsky M. Intubated ureterotomy for ureteral obstruction following radiotherapy and radical hysterectomy. Scand J Urol Nephrol 1993;27:135-137.

3. Debled G, Mercier G. Pelvic retroperitoneal sclerosis caused by radiation therapy for a uterine fibroma. Acta Urol Belg 1978;46:23-31.

4. Lukka H, Warde P, Pickles T, et al. Controversies in prostate cancer radiotherapy: consensus development. Can J Urol 2001;8:1314-1322.

5. Jacobs JA, Rosenthal RS, Shaw JL. Localized ureteral fibrosis: an unrecognized complication of radiation therapy for prostatic carcinoma. J Urol 1976;115:610-611.