Ten-Year Outcomes of Moderately Hypofractionated IMRT in Prostate Cancer

Conventionally, prostate cancer has been treated with intensity modulated radiation therapy (IMRT) administered over eight to nine weeks. However, about 20 years ago Cleveland Clinic pioneered a new technique, moderately hypofractionated IMRT — delivering slightly higher doses of radiation over a shorter time, under six weeks.

Since then, hundreds of prostate cancer patients at Cleveland Clinic have been treated with moderately hypofractionated IMRT. How have they fared?

“Tumor control outcomes seem to be similar to the historic standard of care, and the toxicity profile seems to be quite favorable,” says Rahul Tendulkar, MD, a radiation oncologist at Cleveland Clinic Cancer Center. “These results seem to alleviate concerns that higher doses per treatment would cause late side effects.”

Dr. Tendulkar co-authored a study on these outcomes, to be presented at the 2018 ASTRO Annual Meeting in San Antonio.

“This is the largest reported single-institutional series of hypofractionated IMRT for prostate cancer with more than 10 years of follow-up,” he says. “Hypofractionated IMRT has generally not been adopted across the U.S. due to lack of data about long-term outcomes. This study may help change that.”

Relapse-free survival across risk groups

The study sample included 854 patients with localized prostate cancer treated with moderately hypofractionated IMRT (70 Gy in 28 fractions at 2.5 Gy/fraction) between 1998 and 2012. The median follow-up was 11.3 years (maximum: 19 years).

Patients were grouped by National Comprehensive Cancer Network (NCCN) classifications:

• Low risk (LR), n=266
• Favorable intermediate risk (FIR), defined as having a single NCCN intermediate risk factor, n=238
• Unfavorable intermediate risk (UIR), defined as having multiple NCCN intermediate risk factors, n=106
• High risk (HR), n=244

Biochemical relapse-free survival at 10 years was 71 percent overall — 88, 78, 71 and 42 percent of LR, FIR, UIR and HR patients, respectively.

Clinical relapse-free survival at 10 years was 95, 91, 85 and 72 percent of LR, FIR, UIR and HR patients, respectively.

Overall survival at 10 years was 69 percent. (Ten-year mortality due to prostate cancer was 6.8 percent overall — 2, 5, 5 and 15 percent of LR, FIR, UIR and HR patients, respectively.)

Long-term genitourinary or gastrointestinal toxicity grade 3 or higher, such as urethral stricture or rectal bleeding requiring treatment, remained low with 10-year cumulative incidences of 2 percent and 1 percent, respectively.

Shorter course of treatment worth a longer look

“These data suggest that when radiation therapy is delivered in a very precise way to patients with prostate cancer, giving higher doses per treatment seems to result in favorable outcomes, not to mention a more convenient treatment schedule,” says Dr. Tendulkar.

That applies even to patients in higher risk groups, he notes. Including data from high-risk patients is one strength of this study. So is studying only patients treated at one medical center, according to the same institutional care paths and with stringent quality control.

“We hope that this research will help raise the confidence of radiation oncologists who have been hesitant to adopt a shorter course of treatment for prostate cancer patients,” says Dr. Tendulkar. “We have seen excellent oncological outcomes long-term, with low incidences of toxicity. A fractionated schedule appears to be acceptable for patients across all risk groups.”