Conversations With Prostate Cancer Experts

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Hypofractionated Radiation For Prostate


Prostatepedia talks with Dr. W. Robert Lee, of Duke University Medical Center about hypofractionated radiation therapy. (Read the interview.)

Hypofractionation is a form of external radiation therapy that uses fewer, larger doses per fraction. Historically, the conventional radiation dose for most solid tumors is 1.8 to 2 Gray per day. (Gray is just the scientific term to measure the dose.) That conventional dose comes out of the French school of radiotherapy that dominated radiotherapy in the 1940s and 1950s and made its way over to the United States. Most patients treated with external radiation therapy for prostate cancer in 2016 are treated five days a week for eight or nine weeks.

There is some evidence that fewer, larger doses may, in fact, be better. Some studies have been designed to prove that hypofractionation is better, but the results of several studies have failed to demonstrate that theory. Other studies have been designed to determine if hypofractionation is “no worse than” conventional fractionation; these are known as noninferiority studies. Noninferiority studies are used to show that we can accomplish the same objective with a shorter, more convenient treatment.

I’ve just published a paper in the Journal of Clinical Oncology (April 2016) showing that you can accomplish the same thing with hypofractionation in five and a half weeks versus eight and a half weeks. There is another study from the United Kingdom, which was published in June 2016, which shows that you can accomplish the same thing in a four-week schedule that you can with an eight-and-a-half.week schedule. The results from all of these noninferiority studies are consistent: they show that you can accomplish the same objective in four or five weeks versus eight or nine weeks.

Another hypofractionation approach is stereotactic body radiation therapy (SBRT), which is an example of extreme hypofractionation. You get four to five treatments over a period of one to two weeks rather then four to five weeks. This is an emerging approach. We’ve been doing SBRT at Duke University since 2009 and I think it is safe, but it has yet to be compared to more traditional treatment in a rigorous manner. To repeat, we don’t have rigorous comparisons of SBRT to other definitive radiotherapy options, but they’re forthcoming.

Is a shorter course better for patients just for financial reasons, or is it also just more convenient?

Shorter courses are unambiguously more convenient for patients; in 25 years of practice I have never had a patient request longer courses of treatment.

Do patients usually travel to a radiation therapy center?

Yes. I tell men that, “We’re working on it, but we still haven’t figured out a way to bring the machine to you. You have to come to the machine.” There are significant economic advantages with shorter courses as well. In our current healthcare system, value is increasingly important. If you can accomplish the same thing with fewer resources, less time, and more patient convenience, then that is something you should do.

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Radiation Therapy

This month Prostatepedia is talking about radiation therapy.

Read the issue.

Join us.

Here’s the introduction:

Our radiation therapy discussion begins with Drs. Mack Roach and Michael Zelefsky.

Both discuss the future of radiation therapy and offer insight into escalating radiation to the prostate while minimizing dosing to surrounding normal tissue.

Two developments drive this effort. First, improved imaging provides a more detailed view of the cancer’s extent and its localization within the prostate as well as spread to adjacent structures. Dr. Zelefsky outlines MRI imaging’s impact. Dramatic advances in computer power have also allowed radiation oncologists to develop sophisticated treatment planning software. We can calculate with more precision radiation doses to be delivered to the cancer versus to surrounding normal tissue.

Radiation therapists can also focus external beam radiation with greater precision, leading to IMRT and Cyberknife. These techniques use high-energy photons.

We also developed approaches like brachytherapy and proton beam that augment or compete with photon-based treatments. Further progress in intensifying radiation dose may be limited. Drs. Roach and Zelefsky’s comments on these trends are well balanced.

Another trend is to shorten treatment duration. Current treatment plans require eight to nine weeks. Dr. W. Robert Lee outlines two randomized trials that show four to five and a half weeks of treatment is not inferior to eight to nine weeks of treatment. (Increasing daily radiation doses, a strategy called hypofractionation shortens treatment duration.) Shorter treatments are more convenient for patients. Larger doses per session may also reduce costs as radiation oncologists are paid per treatment session.

Stereotactic body radiotherapy (SBRT) is another way to shorten treatment duration. SBRT delivers five treatments over a week and a half. SBRT is at an earlier development stage; we have no randomized trials proving it is better than or equal to standard fractionation or hypofractionation. SBRT has theoretical advantages, as Dr. Zelefsky comments. Early results are promising, but SBRT’s full potential is still being explored.

Dr. Sean McBride’s clinical trial combines SBRT with cutting-edge hormonal therapy in patients with locally advanced disease at very high risk of recurrence after surgery: Gleason 8-10, a PSA >20, extracapsular spread, or cancer invasion into the seminal vesicles or lower part of the bladder.

Disappointingly, current adjuvant hormonal therapy for radiation typically uses LHRH agonists. Xtandi (enzalutimide) and Zytiga (abiraterone) have revolutionized metastatic prostate cancer treatment. Adding both to adjuvant hormonal treatment is persuasive. McBride’s trial uses an LHRH agonist with Zytiga (abitraterone) and a new drug called apalutamide (ARN 509). Apalutamide’s (ARN-509) mechanism of action is similar to Xtandi’s. This combination is frontline treatment for advanced metastatic prostate cancer, but in this trial, it is applied as adjuvant hormonal therapy for locally advanced prostate cancer. This trial promises to revolutionize treatment for locally advanced disease.

I’m very interested in metformin use for prostate cancer. In my clinic, we use metformin when we start hormPp_August_2016_V1_N12_Thumbonal therapy: a randomized trial shows that it reduces metabolic syndrome risk for men on hormonal therapy. Dr. Zelefsky observes that during radiation, patients on metformin have a reduction in distant metastases, risk of dying of prostate cancer, and risk of castrate resistance. This is retrospective data, though; these advantages need to be tested in a randomized controlled trial.

– Charles E. Myers, Jr., M