(Radiology. 2000;217:215-218.)
© RSNA, 2000
Rectal Bleeding after Radiation Therapy for Prostate Cancer: Endoscopic Evaluation1
Erin M. Moore, MD,
Thomas J. Magrino, MD and
Peter A. S. Johnstone, MD
1 From the General Surgery Department (E.M.M., T.J.M.) and the Clinical Investigation Department (P.A.S.J.), Naval Medical Center San Diego, Suite 5, 34800 Bob Wilson Dr, San Diego CA 92134-1014 and the Radiation Oncology Division, University of California, San Diego (P.A.S.J.). From the 1999 RSNA scientific assembly. Received November 18, 1999; revision requested December 10; revision received March 9, 2000; accepted March 30. Address correspondence to P.A.S.J. (e-mail: pajohnstone@nmcsd.med.navy.mil).
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ABSTRACT
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PURPOSE: To analyze the frequency and clinical importance of proctitis and hematochezia after radiation therapy for prostate cancer.
MATERIALS AND METHODS: Of 63 patients with prostate cancer treated with curative intent by a single radiation oncologist between July 1, 1993, and December 31, 1997, 30 were asymptomatic, but 33 had heme-positive digital rectal examination (DRE) results or hematochezia at routine follow-up. Twenty-six of these patients underwent endoscopy of the sigmoid colon or colon for evaluation of these symptoms. Median doses of 60.0 Gy at postoperative radiation therapy and 68.4 Gy at definitive radiation therapy were delivered to four fields daily by using blocking customized on the basis of computed tomographically documented evidence of disease. The Fisher exact test and the Kaplan-Meier method were used to analyze the results.
RESULTS: The frequency of rectal bleeding approached 80% at 3 years after radiation therapy in definitively treated patients. Only 14 patients had proctitis: eight as the only sign, and six in association with other disease. Six patients had other disease without proctitis, and four patients had normal examination findings. The frequency of rectal bleeding in the presence of proctitis was similar to that in the presence of other disease (Fisher exact test, P = .68).
CONCLUSION: Hematochezia or positive DRE findings are frequent sequelae of definitive radiation therapy for prostate cancer; however, causes other than proctitis are often documented at endoscopy. Symptomatic individuals warrant rigorous evaluation to rule out serious coexistent disease.
Index terms: Prostate neoplasms, therapeutic radiology, 844.126, 844.32 • Radiations, injurious effects, complications of therapeutic radiology, 757.47 • Rectum, abnormalities, 757.26, 757.47
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INTRODUCTION
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Prostate cancer is the malignancy with the highest incidence in the United States, with 179,000 new cases in 1999 alone. Eighty-two percent of cases occur in men older than 65 years (1,2). This statistic is most compelling: Prostate cancer is a cancer of older men. It is this population that is at increased risk for other disease, including neoplasms of the colon and rectum, diverticular disease, and various perianal diseases. All of these can manifest as rectal bleeding or heme-positive digital rectal examination (DRE) findings.
A well-recognized complication of pelvic field radiation therapy is proctitis, with a frequency between 5% and 20% according to published series (3–5). Manifestations include tenesmus, bleeding, diarrhea, and fecal incontinence (6). Rectoscopy has been used as an adjunct to dose-volume histograms for the analysis of proctitis (7), but investigators in only one study (8) have used colonoscopy to evaluate postradiation therapy stenosis or hemorrhage, and the number of patients was small. In many cases, symptoms are often dismissed as a self-limited annoyance to patients with little endoscopic data to refute other potential causes of hemorrhage (9–12).
Our purpose, then, was to analyze the frequency and clinical importance of proctitis and hematochezia after radiation therapy for prostate cancer. We prospectively analyzed a cohort of patients referred for evaluation of rectal bleeding or heme-positive DRE findings after adjuvant or definitive radiation therapy for prostate cancer.
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MATERIALS AND METHODS
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Between July 1, 1993, and December 31, 1997, 63 patients underwent radiation therapy with curative intent for prostate cancer by one of the authors (P.A.S.J.). Characteristics of the patients at presentation and of their therapy are included in Table 1. Patients were treated with four-field (opposed anteroposterior and opposed lateral) radiation therapy portals daily. All patients had therapy simulated prior to treatment, and 18-mV-energy therapy was used in all cases.
For patients treated postoperatively, the prostate bed was irradiated, with margins. In all patients receiving radiation therapy to an intact prostate, gland volumes and subsequent dosimetry were determined on the basis of computed tomographic (CT) scans (Fig 1). In late 1996, sufficient sophistication in radiation therapy treatment planning was available so that patients with appropriate conditions could be treated with a three-dimensional conformal technique after immobilization, generally with the patient in the prone position (Fig 2). Daily doses of 1.8–2.0 Gy were delivered for total doses of 60.0–66.0 Gy (median, 60.0 Gy) in postoperative cases and of 66.0–70.0 Gy (median, 68.4 Gy) in definitive cases. Doses were prescribed to a specific isodose (generally 95%–100%).
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Figure 1. Image shows the isodose plan for the four-field technique of definitive irradiation of an intact prostate gland. Gland volume, determined on a CT scan, is outlined in red. Numbers represent isodose percentages.
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Figure 2. Three-dimensional conformal four-field plan for a prone patient as generated by the treatment-planning computer. The prostate volume is red, the rectum (thin arrow) is blue, and the bladder (thick arrow) is yellow. Purple shading represents the 95% isodose line. The posterior part of the rectum and most of the bladder are well spared with this technique.
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Custom blocking was designed at the time of simulation on the basis of barium enema radiographs obtained with or without intravesical administration of contrast material and on the basis of treatment-planning CT scans. Margins of 1.5–2.0 cm were used in designing custom blocks. At no time was circumferential treatment of the rectum with lateral portals or treatment of the anus allowed. Under no circumstances did the radiation therapy portals include the whole pelvis.
During radiation therapy, each patient’s fields and blocks were peer-reviewed weekly at a divisional conference. Following radiation therapy, patients were followed up by the radiation oncologist (P.A.S.J.), with determination of serum prostate-specific antigen levels and with DRE every 3 months for the 1st year, every 4 months for the 2nd year, every 6 months through the 4th year, and annually thereafter.
Patients were referred for endoscopy of the sigmoid colon or colon if they complained of any instance of bright red blood per rectum or had heme-positive stools at DRE. Referral was made because of the risk of concurrent colorectal disease and the relative lack of routine endoscopic evaluation in this population. The decision to perform colonoscopy over sigmoidoscopy was at the discretion of the physician performing the procedure.
All follow-up data are as of January 31, 1998. Median follow-up for the entire population was 11.5 months. Endoscopic results were obtained by reviewing outpatient records in the departments of radiation oncology, gastroenterology, and general surgery (Naval Medical Center San Diego, Calif).
The dependence of proctitis on the pattern of rectal bleeding was determined by using the Fisher exact test. The Kaplan-Meier method was used to determine the likelihood that rectal bleeding was a function of the time after radiation therapy.
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RESULTS
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Of these 63 patients, 33 (52%) developed symptoms of hematochezia or had heme-positive DRE findings. The remaining 30 patients had heme-negative findings. Five of the 33 patients with positive findings were lost to follow-up, one had complaints of rectal bleeding prior to irradiation, and another refused endoscopic evaluation. The remaining 26 patients are the subject of this article.
The general surgery service examined 19 patients, and the gastroenterology service examined seven. Colonoscopy was performed in 17 (65%) of 26 patients, and sigmoidoscopy was performed in nine (35%) of 26 patients. Of this cohort, 19 (73%) developed rectal bleeding, and seven (27%) had heme-positive DRE findings as first manifestations. Latency from the end of radiation therapy to endoscopic evaluation is used as a surrogate for latency to the onset of symptoms because of the frequency of routine follow-up and the rapid evaluation after consultation. Median latency from the end of radiation therapy to endoscopic evaluation was 12 months. Table 2 reveals the findings at endoscopy for referred patients.
In an effort to determine whether disease other than proctitis was an independent source of rectal bleeding, patients’ endoscopic findings were compared (Table 3). By applying a Fisher exact test, the dependence of proctitis on the pattern of rectal bleeding rendered a P value of .68. Thus, there was no difference in the proportions of patients with and patients without proctitis who experienced rectal bleeding.
Because total dose is a prognostic factor for toxic reactions to irradiation of normal tissues and because patients treated postoperatively were treated with doses that were lower than those of patients treated definitively, further analysis was performed of the likelihood of bleeding symptoms after definitive radiation therapy. Figure 3 is a Kaplan-Meier plot of the likelihood of rectal bleeding as a function of time after radiation therapy. Note that the likelihood of any symptom of rectal bleeding approaches 80% at 3 years.
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Figure 3. Kaplan-Meier plot shows that the likelihood of rectal bleeding symptoms after definitive radiation therapy for prostate cancer approaches 80% at 3 years, which is greater than previously reported data, which showed a frequency of only 60% at 3 years if more than 40% of the anterior part of the rectum was within the irradiated field.
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After subspecialty evaluation, patients continued to be followed up routinely by the radiation oncology service. Table 4 outlines the chronic symptoms in these patients. Only two (8%) of the 26 patients, both with frequent episodic bleeding, required routine therapy with mesalamine suppositories. At the time this article was written, no patient required laser therapy or other surgical procedures to treat the symptoms of proctitis.
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DISCUSSION
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Rectal bleeding is a known complication of pelvic radiation therapy. Modern radiation therapy practices, including the three-dimensional conformal technique and custom blocking, have been shown to decrease the amount of rectum in the radiation therapy portal. Because of this decreased rectal exposure, some protocols increase the dose to the prostate and thus to the anterior part of the rectum. Dose-volume histograms have been studied extensively, and the nature and timing of the radiation dose have been analyzed to provide the maximum safe dose to the cancerous prostate while minimizing the risk of late rectal complications (5,7). Use of these techniques among our treatment population corroborates our findings that, despite the presence of rectal symptoms in more than three-quarters of our patients at 3 years, only two patients required continuing mesalamine suppository therapy, and none required laser therapy at the time this article was written. It must be noted that the high proportion of patients with rectal symptoms is a function of our conservative definition of rectal bleeding, that is, a single episode of bright red blood per rectum or a positive guaiac test at DRE resulted in referral for endoscopy.
While many authors have attempted to predict the severity of proctitis relative to the location and total dose of radiation therapy (3,5,7), to our knowledge, none have ruled out other potential causes of bleeding in their patient populations (10,13). Similarly, we know of no studies of proctitis associated with rectal bleeding after radiation therapy that delineate whether the study population was examined with endoscopy prior to irradiation (14). Some (11) have gone so far as to conclude that the majority of patients with postradiation therapy bleeding should be reassured that eventual spontaneous healing is likely to occur and that they should be cautioned against invasive treatment unless absolutely necessary.
Nonetheless, these bleeding symptoms occur in a population of predominantly older men who are subject to various other diseases, including colon and rectal neoplasms, diverticulosis, and perirectal disease. All of these can manifest with a pattern similar to that of radiation-induced proctitis. The current consensus regarding the screening and detection of colon and rectal neoplasms clearly indicates that men older than 50 years without prior personal or extensive family history of gastrointestinal malignancy should undergo DRE yearly and DRE with flexible sigmoidoscopy every 5 years (15). Positive DRE findings should be followed by sigmoidoscopy or colonoscopy until the source of bleeding is found.
Patients with prostate cancer after radiation therapy are no different from the normal, age-matched population in terms of the risk of colorectal abnormalities (16). While it is true that hematochezia or positive DRE findings are frequent sequelae of definitive radiation therapy and that severe symptoms are infrequent, other potentially important clinical causes are often documented at endoscopy. Those causes are independent of proctitis as a potential source of rectal bleeding. Patients should therefore undergo endoscopy if they have rectal bleeding or heme-positive DRE findings at presentation after radiation therapy for prostate cancer to avoid missing such coexistent disease.
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FOOTNOTES
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Abbreviation: DRE = digital rectal examination
The Chief, Bureau of Medicine and Surgery, Navy Department, Washington, DC, Clinical Investigation Program sponsored this report no. S97-053, as required by NSHSBETHINST 6000.41A. The opinions and assertions contained herein are those of the authors and are not to be construed as official or as representing the views of the United States Navy or Department of Defense.
Author contributions: Guarantor of integrity of entire study, P.A.S.J.; study concepts and design, P.A.S.J.; definition of intellectual content, E.M.M., T.J.M., P.A.S.J.; literature research, E.M.M.; clinical studies, P.A.S.J., E.M.M.; data acquisition and analysis, P.A.S.J., E.M.M.; statistical analysis, E.M.M.; manuscript preparation, E.M.M.; manuscript editing and review, P.A.S.J., T.J.M.
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ABSTRACT
INTRODUCTION
