Radiation proctopathy in the treatment of prostate cancer

doi:10.1016/j.ijrobp.2006.07.1386

International Journal of Radiation OncologyBiologyPhysics

Volume 66, Issue 5, 1 December 2006, Pages 1294-1305

https://doi.org/10.1016/j.ijrobp.2006.07.1386 Get rights and content

Purpose: To compile and review data on radiation proctopathy in the treatment of prostate cancer with respect to epidemiology, clinical manifestations, pathogenesis, risk factors, and treatment.

Methods: Medical literature databases including PubMed and Medline were screened for pertinent reports, and critically analyzed for relevance in the scope of our purpose.

Results: Rectal toxicity as a complication of radiotherapy has received attention over the past decade, especially with the advent of dose-escalation in prostate cancer treatment. A number of clinical criteria help to define acute and chronic radiation proctopathy, but lack of a unified grading scale makes comparing studies difficult. A variety of risk factors, related to either radiation delivery or patient, are the subject of intense study. Also, a variety of treatment options, including medical therapy, endoscopic treatments, and surgery have shown varied results, but a lack of large randomized trials evaluating their efficacy prevents forming concrete recommendations.

Conclusion: Radiation proctopathy should be an important consideration for the clinician in the treatment of prostate cancer especially with dose escalation. With further study of possible risk factors, the advent of a standardized grading scale, and more randomized trials to evaluate treatments, patients and physicians will be better armed to make appropriate management decisions.

Introduction

In 2006, the number of new cases of prostate cancer is estimated to be 234,460 in the United States (1) and well over 500,000 worldwide, accounting for approximately one-third of all cancers in men. Radiotherapy is an established treatment modality for localized prostate cancer and for selected high-risk postoperative patients. The radiation dose–response relationship for prostate cancer has been studied (2) and is widely accepted, but limited with conventional radiation techniques by increased toxicity of proximal structures including the rectum and bladder (3). The advent of three-dimensional conformal radiotherapy (3D-CRT) (4) and more recently intensity-modulated radiotherapy (IMRT) has allowed the delivery of higher doses of radiation to the prostate with less radiation dose to surrounding structures (5). Furthermore, we recently showed the reduction of rectal toxicity secondary to IMRT (6). Despite recent advancements, the rectum and bladder continue to receive significant radiation, and dose escalation, although more efficacious for prostate cancer, has led to an increase in side effects involving these structures (7). Radiation proctopathy has become a major focus for both patients and clinicians with its adverse effects on patient quality of life. We will review radiation proctopathy with respect to its clinical and pathologic features as well as its treatment.

Section snippets

Epidemiology and clinical manifestations

Radiation proctopathy is defined as symptomatic radiation-induced damage to the lining of the rectum that commonly occurs as a result of radiotherapy for prostate cancer. Depending on the treatment technique, the patients may have symptoms of radiation-induced injury to gastrointestinal structures more proximal to the rectum including the small bowel and sigmoid colon (radiation enteropathy). These symptoms may contribute and even mask symptoms attributed to rectal damage alone. Furthermore,

Radiation-related risk factors

Factors associated with the development of rectal toxicity after radiotherapy for prostate cancer are variable and may be categorized as they relate to radiation delivery or patient characteristics (Table 2).

The correlation between radiation dose and rectal toxicity is somewhat intuitive and well accepted. Studies in dose escalation using 3D-CRT have shown less late rectal toxicity than previous conventional doses, but a significant risk of rectal toxicity remains and is likely dependent on the

Patient-related risk factors

The effect of patient-related factors (Table 2) on the incidence of radiation proctopathy is argued by some (55, 56) but is not yet clear. Diabetes has been suggested as a predictive factor for late Grade 2 gastrointestinal and genitourinary complications. In a study of over 900 patients followed over a median of 36 months, diabetes among other factors such as dose, and presence of rectal shielding were independent predictors of late Grade 2 gastrointestinal toxicity (55). In the same study,

Workup

Taking a detailed history is the most important tool in the diagnosis and eventual treatment of radiation proctopathy. Patients may present months to years after radiotherapy, and the progression of symptoms over this time is imperative to define the severity of disease and impact on the patients’ quality of life.

Colonoscopy is most useful in documenting radiation proctopathy vs. other causes of similar symptoms. Rarely, however, do physicians grade the disease based on a unified system, and

Treatment

Effective preventive therapies for radiation proctopathy have proven difficult to uncover. Amifostine, an established radio-protectant, has been shown to reduce both acute and late pelvic radiation toxicity (62) when applied systemically. Its direct intrarectal application has shown promising results as well (63). Recently, the effects of amifostine have been suggested to utilize a nuclear factor kappa B (NF-κB)-dependent pathway, leading to the expression of genes integral to tissue

Quality of life

The evaluation of radiation for the treatment of localized prostate cancer mandates discussion of the potential impact on patient quality of life (94, 95). When comparing surgery with external beam radiation (95, 96), significant trade-offs in quality of life should be considered and presented to the patient to make a more informed decision. For example, prostatectomy is generally associated with immediate urinary and sexual symptoms that may improve over time, in comparison to external

Direction of research

The development of novel treatment strategies in prostate cancer has significant implications in the discussion of radiation proctopathy. With better understanding of molecular pathways leading to prostate cancer initiation and progression, the addition of chemotherapy regimens, gene therapy strategies, and numerous biologic modifiers that target specific pathways is currently under investigation. These potential treatments may serve in selected cases as alternatives to high-dose radiation or

Conclusion

With more advanced screening techniques and earlier diagnosis, more patients are being treated for localized prostate cancer with radiotherapy. Although advanced delivery techniques including IMRT may help to decrease radiation dose to surrounding tissues, radiation proctopathy will continue to be a concern as we dose escalate to a much higher level. As more information becomes available regarding risk factors, diagnosis, and treatments for radiation proctopathy, clinicians and patients will be

Acknowledgment

The authors wish to thank Shirley Clark for her assistance in the preparation of this manuscript. Dr. Teh is the recipient of a Methodist Hospital Research Institute research grant.