Hypofractionated radiation therapy for localized prostate cancer: an update


Within the past year, we have reviewed several major randomized clinical trials comparing hypofractionated radiation therapy to conventionally fractionated radiation therapy for primary treatment of localized prostate cancer. To recap:

The CHHiP Study (reviewed here and published here) proved that 60 Gy delivered in 20 fractions was not inferior to 74 Gy in 37 fractions in terms of cancer control, patient-reported toxicity, or physician-reported toxicity.

The Fox Chase trial (reviewed here), which focused on men with intermediate- and high-risk prostate cancer, proved that 70.2 Gy delivered in 26 fractions was not inferior to 76 Gy in 38 fractions. All functional outcomes (urinary, bowel, and sexual) were similar in the long term.

RTOG 0415 (reviewed here), which focused on men with low-risk prostate cancer, proved that 70 Gy delivered in 28 fractions was not inferior to 73.8 Gy in 41 fractions in terms of cancer control, rectal toxicity, or urinary toxicity.

Finally, the HYPRO trial, which enrolled predominantly (> 70 percent) high-risk patients and some intermediate-risk patients, previously published its toxicity analysis (reviewed here). They have now released their findings about cancer control (available here). Patients assigned to hypofractionation received 64.6 Gy in 19 fractions; conventional fractionation was 78 Gy in 39 fractions. Radiation was delivered using 3D-CRT rather than IMRT. After a median 60 months of follow-up, they report:

  • Treatment failure occurred in 20 percent of the patients receiving hypofractionated radiation vs. 22 percent of those who received conventional fractionation. No significant difference.
  • 5-year relapse-free survival was 80.5 percent among the hypofractionated radiation patients vs. 77.1 percent among the conventionally fractionated radiation patients. No significant difference.

They conclude:

Hypofractionated radiotherapy was not superior to conventional radiotherapy with respect to 5-year relapse-free survival. Our hypofractionated radiotherapy regimen cannot be regarded as the new standard of care for patients with intermediate-risk or high-risk prostate cancer

It’s difficult to understand the reticence of the HYPRO investigators to adopt hypofractionation as the new standard of care, and W. Robert Lee (in an accompanying editorial) explains the apparent discrepancy. He notes that the HYPRO trial set a goal of raising the relapse-free survival by 10 points, from 70 percent to 80 percent using hypofractionation. While it achieved over 80 percent control, it was not a difference of 10 points. Therefore, they could not prove that the hypofractionated protocol was superior. The other trials only attempted to prove that hypofractionation was not inferior, which they all did.

Patients, who are not as concerned with the statistical niceties of the distinction between inferiority studies and superiority studies, have reason to rejoice over these results. Collectively, these studies mean that radiation treatments for localized disease (low-risk, intermediate-risk, and high-risk) can be done as effectively and with about the same toxicity as the typical 9-week IMRT schedule.

It’s worth mentioning that hypofractionation is gaining acceptance for other kinds of cancer as well, such as breast cancer. Extreme hypofractionation, such as that used in stereotactic body radiation therapy (SBRT), has been used effectively and with low toxicity in prostate and other cancers, but has not yet been proven in a randomized clinical trial.

There are some appropriate cautions that patients need to be aware of:

  • Hypofractionation can be very safe if the radiation oncologist is using the latest fast and accurate linear accelerators that are designed to deliver the higher doses.
  • State-of-the-art image guidance, using such tools as fiducials, radio-transmitters, and cone-beam CT imaging, is equally important.
  • And nothing is more important than an experienced radiation oncologist who takes meticulous care to optimize the treatment plan with respect to dose constraints for organs at risk.

This is a hard sell to many radiation oncologists in private practice because it hits them in the pocketbook. On the other hand, if they don’t get on board, they will be left in the dust. Some patients may nevertheless opt for the more conventional treatment, but there is no reason that the hypofractionation option should not be discussed.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

 

 

3 Responses

  1. It would have been interesting to see how these hypofractionation regimens would have compared to escalated dosage (79.2-86.0 Gy) conventionally fractionated regimens with and without ADT. Most guys I know who’ve recently received IMRT/IGRT are getting higher dosages than your studies incorporated.

  2. Bravo, Allen! Nice work in putting this all in perspective.

  3. RobC:

    Unfortunately, that comes with the territory: by the time we get long-term results on radiation studies, our knowledge and technological advances make the findings somewhat obsolete.The HYPRO study used the highest level of conventional fractionation — 78 Gy/39 fx, which is close to contemporary levels. Unfortunately, they did not use contemporary IGRT/IMRT technology to administer it. But hypofractionation allows doctors to administer much higher biologically effective doses (BEDs) while keeping the nominal dose, and especially the dose experienced by organs at risk, much lower. So, the BEDs to cancer cells were at contemporary levels in the hypofractionated groups in the CHHiP and RTOG 0415 studies, and were higher than contemporary conventional doses in the hypofractionated groups in the Fox Chase and HYPRO studies.

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