The risk of developing more serious long-term urinary and bowel health issues may be higher in men undergoing radiation therapy for prostate cancer who experience side effects early in treatment, according to a recent study published by Nikitas et al in The Lancet Oncology. The findings highlighted the significance of identifying strategies to better manage acute toxicities and help improve long-term outcomes and quality of life among patients with prostate cancer.
Background
Prostate cancer is the most common cancer type among men. Radiation therapy serves as a key treatment for localized prostate cancer, often involving higher doses to better control the disease. Although this approach effectively manages prostate cancer, it can also harm nearby healthy tissues, resulting in acute and late-term side effects for patients.
Acute toxicity refers to side effects that occur during treatment or within the first 3 months following its completion; they are typically temporary. Common urinary side effects include increased frequency of urination, difficulty urinating, and discomfort during urination. Bowel-related side effects may include softer stools, diarrhea, and rectal discomfort during bowel movements. Conversely, late toxicity can appear months or even years following treatment and can last for years. Late urinary toxicities include narrowing of the urethra and the presence of blood in the urine. Late bowel toxicities include blood in the stool or an ulcer in the wall of the rectum. These issues often can have a larger impact on a patient’s quality of life compared with acute side effects.
“Men with prostate cancer are living longer than ever, and our goal is to reduce the risk of late toxicities, such as difficulty urinating or rectal bleeding, that can impact a patient’s quality of life for years,” stressed senior study author Amar Kishan, MD, Executive Vice Chair of Radiation Oncology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and an investigator at the UCLA Health Jonsson Comprehensive Cancer Center. “This study highlights innovations we’re developing, [including] using smaller treatment margins in prostate radiation to minimize early side effects, that can lead to lasting benefits by also reducing the risk of long-term complications for patients,” he continued.
While both acute and late toxicities are caused by the effect of radiation therapy on healthy tissues, the connection between the two has been poorly studied, particularly using large-scale data.
Study Methods and Results
In the study, investigators analyzed data from six randomized phase III clinical trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy involving over 6,500 patients. The trials shared detailed, individual-level data on the short- and long-term side effects affecting the urinary and bowel systems in this patient population.
Patients who experienced moderate acute urinary side effects within the first 3 months following radiation therapy were nearly twice as likely to develop urinary complications years later compared with those who didn’t experience early symptoms. Similarly, the patients who reported early bowel side effects had nearly twice the risk of chronic bowel issues. The patients with early urinary or bowel issues were also more likely to report significant declines in their ability to manage daily activities and overall quality of life. The investigators revealed that experiencing acute toxicity increased the rate of late toxicity from 7.5% to 12.5% for urinary toxicity and from 12.7% to 22.5% for bowel toxicity.
The risks of experiencing a clinically significant decline in urinary or bowel quality of life were a respective 1.4 and 1.5 times as high among men who had moderate acute urinary or bowel toxicity.
Conclusions
“These results show that acute toxicities following prostate radiotherapy are associated with late toxicities months and years later,” emphasized lead study author John Nikitas, MD, a resident in the Department of Radiation Oncology at UCLA Health. “This underscores the importance of measures that reduce the risk of acute toxicities, because they may also potentially improve long-term outcomes and quality of life for patients,” he suggested.
The investigators underlined the potential impact of newer techniques to reduce both acute and late toxicities in this patient population.
“Reducing early side effects through advanced techniques like [magnetic resonance imaging]–guided radiation, which allows for more precise targeting of tumors, and urethral-sparing methods, which uses spacers between the prostate to protect surrounding tissues and rectum, could potentially help lower the risk of lasting side effects,” underscored Dr. Kishan.
Despite the findings, the investigators stated that more studies may be needed to determine whether specific strategies to reduce the early side effects of radiation therapy can improve long-term outcomes and whether treating the short-term side effects early can help prevent long-term complications.
Disclosure: The research in this study was supported in part by grants from the National Institutes of Health and the U.S. Department of Defense. For full disclosures of the study authors, visit thelancet.com.
