Hypofractionated radiotherapy effective for localized prostate cancer

Men with localized prostate cancer who received radiation treatments over 4 weeks achieved comparable outcomes as those who received the standard 8-week regimen, according to study results published in Journal of Clinical Oncology.

“We conducted a randomized clinical trial looking at a way of improving radiation therapy for men with intermediate-risk prostate cancer,” Charles N. Catton, MD, radiation oncologist at Princess Margaret Cancer Centre in Toronto, said in a press release. “Using modern external beam radiation therapy techniques that are very precise, we determined there was no noticeable difference between 8- and 4-week treatment regimens in terms of cancer control or side effects of treatment.

Charles N. Catton

“In fact, for some men, the shorter regimen meant slightly fewer persistent side effects, particularly regarding bowel function,” Catton said. “The compressed course of treatment is of great benefit to patients and also to the system in terms of being able to treat more patients in less time.”

The multicenter, randomized, noninferiority trial included 1,206 men with intermediate-risk prostate cancer, none of whom underwent androgen deprivation therapy.

Researchers assigned 608 men to hypofractionated radiotherapy, which consisted of 60 Gy administered in 20 fractions over 4 weeks. The other 598 men received standard radiotherapy, which consisted of 78 Gy administered in 39 fractions over 8 weeks.

Biochemical failure — defined as PSA failure, hormonal intervention, clinical local or distant failure, or prostate cancer-associated mortality — served as the primary outcome.

After median follow-up of 6 years, 109 men assigned hypofractionated therapy and 117 men assigned standard therapy experienced biochemical clinical failure; the majority were PSA failures. Researchers reported 5-year biochemical clinical failure DFS of 85% in both treatment groups.

Ten patients assigned hypofractionated therapy and 12 assigned standard therapy died of prostate cancer. Investigators observed no significant differences in grade 3 or worse late genitourinary and gastrointestinal toxicities between treatment groups.

HemOnc Today spoke with Catton about the study results and their potential implications.

Question: What prompted this research?

Answer: This study was a consequence of improvements in external beam radiation treatment technology that improved the precision of daily radiation delivery. This, in turn, permitted higher doses of radiation to be delivered safely to the prostate. Clinical trials of dose escalation confirmed that higher doses could be administered safely, and that cancer control improved. The downside was that courses of external beam radiation treatment extended from about 6.5 weeks to between 8 and 9 weeks duration. This placed an additional burden on patients and the health care system. The same technology that permits dose escalation will potentially permit dose compression. An 8-week course of treatment could be compressed to 4 weeks by giving a more intense dose of radiation at each daily session. The concerns about daily dose intensification — known as hypofractionation — are that side effects could be worse, the mathematical dosing model used to convert an 8-week course of treatment to 4 weeks could be wrong, and disease control would suffer as a result.

Q: How did you conduct the study?

A: This was a noninferiority randomized controlled trial that compared 4 weeks of external beam radiation with 8 weeks of external beam radiation for 1,206 men with intermediate-risk prostate cancer who chose radiotherapy for their treatment. It was conducted in Canada, Australia and France. Biochemical and clinical cancer control served as the primary endpoint. Secondary endpoints included acute and late toxicity, OS, cancer-specific survival and patient-reported quality of life.

Q: What did you find?

A: With a median follow-up of 6 years, cancer control with 4 weeks of treatment was noninferior to cancer control with 8 weeks of treatment. In both instances, 85% were free of relapse at 5 years. Researchers observed no difference between treatment groups with regard to frequency and severity of bladder side effects that occurred during or after treatment. Slightly more patients who received the 4-week course experienced minor bowel side effects during treatment. However, slightly fewer patients in that group experienced persistent minor and major bowel side effects after treatment.

Q: What are the potential benefits of shorter treatment duration?

A: We concluded that 4 weeks of treatment is a safe and effective alternative to 8 weeks of treatment for men with intermediate-risk prostate cancer who undergo external beam radiotherapy. A 4-week reduction in the duration of treatment will reduce the economic and potentially psychological burden of treatment on patients and their families. A course of radiation given with fewer fractions also will free up radiotherapy resources for other patients to utilize.

Q: Is there reason to think treatment administered over a period even shorter than 4 weeks could be effective? 

A: Yes. Clinical trials are underway investigating 2-week and even 1-week courses of treatment. The results of our study provide encouragement that the concept of hypofractionation is sound, and that trials of more intensive hypofractionation should continue.

Q: Is this approach ready to be adopted, or does more research need to be done to confirm these findings?

A: The results of our study provide strong evidence that a 4-week course of treatment can now be adopted into conventional practice for appropriate patients. This treatment technique is already being adopted as standard in the United Kingdom, Canada and Australia for men with intermediate-risk prostate cancer.

Q: Is there anything else that you would like to mention?

A: Moderately hypofractionated external beam radiotherapy is now a standard option in many jurisdictions for the treatment of low- and intermediate-risk prostate cancer. Further research is required to determine if this technique is also suitable for treating patients with high-risk disease, or if it can be combined with brachytherapy. It is expected that even shorter regimens will be adopted in the future, once the clinical trials investigating these are completed. – by Jennifer Southall

Reference:

Catton CN, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2016.71.7397.

For more information:

Charles Catton, MD, can be reached at Princess Margaret Cancer Centre, OPG Building,

7th Floor, Radiation Oncology, 700 University Ave., Toronto, ON, M5G 1Z5; email: charles.catton@rmp.uhn.on.ca.

Disclosure: Catton reports no relevant financial disclosures.

Men with localized prostate cancer who received radiation treatments over 4 weeks achieved comparable outcomes as those who received the standard 8-week regimen, according to study results published in Journal of Clinical Oncology.

“We conducted a randomized clinical trial looking at a way of improving radiation therapy for men with intermediate-risk prostate cancer,” Charles N. Catton, MD, radiation oncologist at Princess Margaret Cancer Centre in Toronto, said in a press release. “Using modern external beam radiation therapy techniques that are very precise, we determined there was no noticeable difference between 8- and 4-week treatment regimens in terms of cancer control or side effects of treatment.

Charles N. Catton

“In fact, for some men, the shorter regimen meant slightly fewer persistent side effects, particularly regarding bowel function,” Catton said. “The compressed course of treatment is of great benefit to patients and also to the system in terms of being able to treat more patients in less time.”

The multicenter, randomized, noninferiority trial included 1,206 men with intermediate-risk prostate cancer, none of whom underwent androgen deprivation therapy.

Researchers assigned 608 men to hypofractionated radiotherapy, which consisted of 60 Gy administered in 20 fractions over 4 weeks. The other 598 men received standard radiotherapy, which consisted of 78 Gy administered in 39 fractions over 8 weeks.

Biochemical failure — defined as PSA failure, hormonal intervention, clinical local or distant failure, or prostate cancer-associated mortality — served as the primary outcome.

After median follow-up of 6 years, 109 men assigned hypofractionated therapy and 117 men assigned standard therapy experienced biochemical clinical failure; the majority were PSA failures. Researchers reported 5-year biochemical clinical failure DFS of 85% in both treatment groups.

Ten patients assigned hypofractionated therapy and 12 assigned standard therapy died of prostate cancer. Investigators observed no significant differences in grade 3 or worse late genitourinary and gastrointestinal toxicities between treatment groups.

HemOnc Today spoke with Catton about the study results and their potential implications.

Question: What prompted this research?

Answer: This study was a consequence of improvements in external beam radiation treatment technology that improved the precision of daily radiation delivery. This, in turn, permitted higher doses of radiation to be delivered safely to the prostate. Clinical trials of dose escalation confirmed that higher doses could be administered safely, and that cancer control improved. The downside was that courses of external beam radiation treatment extended from about 6.5 weeks to between 8 and 9 weeks duration. This placed an additional burden on patients and the health care system. The same technology that permits dose escalation will potentially permit dose compression. An 8-week course of treatment could be compressed to 4 weeks by giving a more intense dose of radiation at each daily session. The concerns about daily dose intensification — known as hypofractionation — are that side effects could be worse, the mathematical dosing model used to convert an 8-week course of treatment to 4 weeks could be wrong, and disease control would suffer as a result.

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Q: How did you conduct the study?

A: This was a noninferiority randomized controlled trial that compared 4 weeks of external beam radiation with 8 weeks of external beam radiation for 1,206 men with intermediate-risk prostate cancer who chose radiotherapy for their treatment. It was conducted in Canada, Australia and France. Biochemical and clinical cancer control served as the primary endpoint. Secondary endpoints included acute and late toxicity, OS, cancer-specific survival and patient-reported quality of life.

Q: What did you find?

A: With a median follow-up of 6 years, cancer control with 4 weeks of treatment was noninferior to cancer control with 8 weeks of treatment. In both instances, 85% were free of relapse at 5 years. Researchers observed no difference between treatment groups with regard to frequency and severity of bladder side effects that occurred during or after treatment. Slightly more patients who received the 4-week course experienced minor bowel side effects during treatment. However, slightly fewer patients in that group experienced persistent minor and major bowel side effects after treatment.

Q: What are the potential benefits of shorter treatment duration?

A: We concluded that 4 weeks of treatment is a safe and effective alternative to 8 weeks of treatment for men with intermediate-risk prostate cancer who undergo external beam radiotherapy. A 4-week reduction in the duration of treatment will reduce the economic and potentially psychological burden of treatment on patients and their families. A course of radiation given with fewer fractions also will free up radiotherapy resources for other patients to utilize.

Q: Is there reason to think treatment administered over a period even shorter than 4 weeks could be effective? 

A: Yes. Clinical trials are underway investigating 2-week and even 1-week courses of treatment. The results of our study provide encouragement that the concept of hypofractionation is sound, and that trials of more intensive hypofractionation should continue.

Q: Is this approach ready to be adopted, or does more research need to be done to confirm these findings?

A: The results of our study provide strong evidence that a 4-week course of treatment can now be adopted into conventional practice for appropriate patients. This treatment technique is already being adopted as standard in the United Kingdom, Canada and Australia for men with intermediate-risk prostate cancer.

PAGE BREAK

Q: Is there anything else that you would like to mention?

A: Moderately hypofractionated external beam radiotherapy is now a standard option in many jurisdictions for the treatment of low- and intermediate-risk prostate cancer. Further research is required to determine if this technique is also suitable for treating patients with high-risk disease, or if it can be combined with brachytherapy. It is expected that even shorter regimens will be adopted in the future, once the clinical trials investigating these are completed. – by Jennifer Southall

Reference:

Catton CN, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2016.71.7397.

For more information:

Charles Catton, MD, can be reached at Princess Margaret Cancer Centre, OPG Building,

7th Floor, Radiation Oncology, 700 University Ave., Toronto, ON, M5G 1Z5; email: charles.catton@rmp.uhn.on.ca.

Disclosure: Catton reports no relevant financial disclosures.