As many as 50% of patients undergoing pelvic radiation therapy define their quality of life as degraded due to subsequent chronic changes to their bowel function, such as diarrhea or fecal incontinence.1-3 These late effects are common—in some cases, even life-threatening—and clearly significant for patients. But frequently, they go clinically undetected or remain untreated.1-3
This lack of posttreatment symptom management is due, in part, to a widespread use of symptoms-driven diagnoses (eg, chronic proctitis, enteritis, cystitis) rather than making a cause-describing diagnosis.1,4 Persistent inflammation rarely underlies late radiation toxicities, leading some researchers to reject the use of terms denoting inflammatory conditions to describe late radiotherapy-associated toxicities.4
EVOLVING CLINICAL PERCEPTION
Radiotherapy-associated chronic toxicity is frequently seen as an assemblage of indistinct complaints or symptoms, rather than a definable disease. Its effects are “rarely accurately measured or fully appreciated,” reported an international team of researchers led by H. Jervoise N. Andreyev, PhD.4 Late toxicities can be difficult to differentiate from other disorders.
For example, symptom-based (eg, rectal bleeding) toxicity checklists or scales do not measure the duration of symptoms, which is an important consideration when attributing symptoms to prior radiotherapy (eg, rectal bleeding is attributable to radiotherapy only if the anterior rectal wall was irradiated; in up to 33% of cases, postradiotherapy rectal bleeding is due to causes other than the radiotherapy).4
Treatment success is typically defined in terms of tumor control or eradication, rather than the long-term well-being of the patient.5 However, chronic toxicities can arise months or even years after radiotherapy is completed, so oncology treatment teams may never become aware of them, and other clinicians may not attribute them to a history of pelvic radiotherapy.1
Experts have made a concerted effort to move away from describing chronic pelvic radiotherapy-associated toxicities as individual symptoms, recognizing them instead as manifestations of a single phenomenon referred to as pelvic radiation disease.4 Andreyev’s team defined pelvic radiation disease as transient or longer-term problems, ranging from mild to very severe, that arise in noncancerous tissues as a result of radiation treatments to tumors of pelvic origin.4
The development of new symptoms affecting the bowel, urinary tract, sex organs, bones, or skin during or after radiotherapy may be pelvic radiation disease, note Andreyev and colleagues.6 Postradiotherapy rectal bleeding should prompt assessment of other potential manifestations of pelvic radiation disease, such as urinary or fecal incontinence.
The molecular and physiologic mechanisms leading to pelvic radiation disease are complex, and symptoms related to gastrointestinal and urinary tract dysfunction can be diverse, frequently arising from separate lesions within different parts of the GI tract.1,4 Radiotherapy can cause ulceration, acute inflammation, cell death, and edema in healthy nontarget tissues, which can be investigated with flexible rectosigmoidoscopy.6 These injuries can also lead to chronic ischemia and fibrosis, which are predominantly submucosal changes.6
Objective clinical findings do not always match patient-reported symptoms.1,4 Symptoms can include such problems as anal ulceration and bleeding, bloating and constipation, fatigue and lethargy, flatulence, hemorrhoids, insomnia, mucus discharge or steatorrhea (elevated levels of fat in feces caused by diminished intestinal absorption), nausea, abdominal or anal pain, and even the loss of a sense of taste.1 Late rectal bleeding appears to be a direct, dose-dependent side effect of radiation therapy, whereas other chronic toxicities of the urinary tract and intestinal mucosa, including incontinence, appear to be long-term exacerbations of acute toxicities (sometimes referred to as consequential late effects) and are independent of radiation dose.4 Bowel obstruction, fistulas, and secondary cancers triggered by radiation to nontarget tissues represent potentially life-threatening late toxicities stemming from pelvic radiotherapy.1