Stereotactic Body Radiation Therapy: Quality of Life vs. Possible Risks

The evolution of prostate cancer (PCa) treatment often seems like a moving target. Suddenly there’s a revolutionary new treatment, or an exciting development in an existing one. Patients benefit from technological advances, gains in experience, and improved scientific knowledge—but even the most promising must survive the test of time, since unintended consequences can show up many years after what looked like success. This may be especially true when it comes to radiation therapy.

Numerous radiation modalities

For many decades, researchers and clinicians have been searching for the perfect therapy that will destroy PCa without side effects and risks—the so-called Silver Bullet. Radiation has three properties that make this endeavor challenging:

• Radiation scatters and has an effect on nearby healthy tissue and structures it passes through.
• It doesn’t immediately destroy cells; over time it affects their DNA so they stop reproducing, but this can also cause mutations in healthy cells.
• Unlike thermal or chemical ablations that can be visibly monitored as they destroy tumors, the slow work of radiation is difficult to track, measure and prove as it’s occurring.

Because of these attributes, there are now numerous radiation modalities available because of the search to contain, shape, target, or focus it. They include conventional external beam radiation therapy (EBRT), intensity modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3D-CRT), radioactive seed implants (brachytherapy), proton beam, and stereotactic body radiation therapy (SBRT). Dr. James Yu from Yale University states that today, radiation can be targeted with very little error margin, but he points out that there still can be side effects depending on the area being treated; the prostate has particular drawbacks because of the prostate’s proximity to the bladder and rectum, with the urethra passing through it and neurovascular bundles all around it, making it tricky to radiate.[i]

Nevertheless, radiation offers distinct advantages for the appropriate PCa patient. It’s noninvasive, so it’s a good option for nonsurgical candidates. It’s generally covered by Medicare and most insurance, making it affordable. Its success rates for the right patients are comparable to surgery and ablation.

Stereotactic body radiation therapy (SBRT, Cyberknife®)

One of the newer types of beam radiation, stereotactic body radiation therapy (SBRT), is gaining competitive ground over other methods. A robotically administered form called Cyberknife® is probably best known to patients. Its unique system sets it apart:

1. To assure accuracy and compensate for patient movement, a couple of weeks before treatment harmless tiny gold markers (fiducials) are implanted in the prostate. These will enable the flexible robotic system to track and aim at the tumor.
2. The movable robot enables doctors to plan the best angles to enter and exit the body to minimize impact on healthy tissue while maximizing precise radiation to the tumor.
3. Because the treatment involves high doses of radiation with relative precision compared to traditional beam radiation, treatment is complete in only 4-5 sessions instead of 30-40.

Cancer control and quality of life

How close does SBRT come to being a Silver Bullet? I found two studies that followed patients for 5+ years, monitoring their recovery and quality of life experiences using the Expanded Prostate Cancer Index Composite (EPIC) which covers urinary, bowel and sexual quality of life following PCa treatment.

The first study by King, et al.[ii] included 864 patients followed for an average of 36 months, with 194 evaluable out to 5 years. Median patient age was 69. The authors report that on average, urinary and bowel function declined most notably during the first 3 months after treatment (not unusual for radiation) but had mostly recovered by 6 months and “…actually showed improvement over baseline starting at around 3 years,” remaining durable. On average, sexual function also declined early and leveled off for about 2 years, then declined gradually – which the authors felt was expectable given that erectile dysfunction tends to increase as men age into their 70s. Since the purpose of the study was quality-of-life related, cancer control rates (freedom from biochemical recurrence) were not reported.

The second study by Katz, et al.[iii] reports on 304 PCa patients (low, intermediate and high risk) who had SBRT and were followed for up to 6 years for cancer control and quality of life. As with the King study, patients experienced early decrease in urinary and bowel function but later returned to baseline; an overall decrease of 20% in sexual quality of life occurred. While there were no severe (Grade III or IV) early complications, late urinary Grade II complications occurred in 4% of patients who received a lower radiation dose and 9% of those who had a higher dose; 2% of those in the higher dose group had late Grade III urinary toxicities. Late Grade II rectal events were seen in 2% of lower dose patients and 5% of higher dose patients. Cancer control rates (biochemical recurrence-free) at 5 years from treatment were 97% for low-risk, 90.7% for intermediate-risk, and 74.1% for high-risk patients.

What other studies report

I have previously written blogs on patient-reported radiation toxicities, ED after radiation, post-radiation bladder cancer risk, and other increased chances of secondary cancers. As Dr. Yu noted, the prostate gland has important, delicate organs as close neighbors, which is a drawback for radiation treatment. Other studies of SBRT for PCa raise concerns not noted in the above two studies. For example, Duvergé, et al. (2017) state that the radiation dose limitations vary in the literature for bladder exposure to high-dose radiation.[iv] Wang, et al. (2018) linked higher radiation doses with urinary and rectal bother as far as 2 years out for up to 11% of patients at very high doses.[v] Wahl, et al (2016) write that “…despite tight margins and full translational and rotational corrections provided by robotic stereotactic body radiotherapy, we find that interfraction anatomical variations can lead to a substantial increase in delivered rectal doses during prostate stereotactic body radiotherapy.”[vi]

Conclusion

I find that there is a great deal of consensus in the literature on SBRT for the treatment of low- and intermediate-risk PCa is generally linked with high rates of biochemical PCa control, and low rates of severe toxic events. It is therefore an appropriate treatment choice for localized, favorable risk disease. The caution I have is the same as for all forms of radiation in such an anatomically sensitive area of the pelvic bed where the prostate gland has such close neighbors. Healthy cells are considerably more radiation-resistant than cancer cells, hence the odds will always be in favor of them not being damaged by radiation. However, if mutations are going to occur, it can take many years for them to become malignant. Is a 5-year study of SBRT long enough to observe unintended consequences?

Perhaps only time will tell.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Yu, James B. “Dr. Yu on the Drawbacks of Radiation Therapy in Prostate Cancer.” OncLive, June 5, 2019. https://www.onclive.com/onclive-tv/dr-yu-on-the-drawbacks-of-radiation-therapy-in-prostate-cancer [ii]King CR, Collins S, Fuller D, Want PC et al. Health-related quality of life after sterortactic body radiation therapy for localized prostate cancer: Results from a multi-insitutional consortium of prospective trials. Int J Radiation Oncol Biol Phys. 2013;87(5):939-945. [iii] Katz AJ, Santoro M, Diblasio F, Ashley R. Stereotactic body radiotherapy for localized prostate cancer: disease control and quality of life at 6 years. Radiat Oncol. 2013 May 13;8:118. [iv]Duvergé L, Castelli J, Lizée T, de Crevoisier R, Azria D. [Doses to organs at risk for conformational and stereotactic radiotherapy: Bladder]. Cancer Radiother. 2017 Oct;21(6-7):597-603. [v] Wang K, Chen RC, Kane BL, Medbery CA et al. Patient and Dosimetric Predictors of Genitourinary and Bowel Quality of Life After Prostate SBRT: Secondary Analysis of a Multi-institutional Trial. Int J Radiat Oncol Biol Phys. 2018 Dec 1;102(5):1430-1437. [vi] Wahl M, Descovich M, Shugard E, Pinnaduwage D et al. Interfraction Anatomical Variability Can Lead to Significantly Increased Rectal Dose for Patients Undergoing Stereotactic Body Radiotherapy for Prostate Cancer. Technol Cancer Res Treat. 2017 Apr;16(2):178-187.