Is Prostate SBRT a Valid Option? The Evidence is In, and It's Good News | Varian

Is Prostate SBRT a Valid Option? The Evidence is In, and It's Good News

Is Prostate SBRT a Valid Option? The Evidence is In, and It's Good News

After decades of data collected on thousands of patients, evidence points to SBRT as a safe and effective option for the treatment of early- to mid-stage prostate cancer. This article throws new light on several key studies to help answer any lingering questions and assuage remaining concerns among the radiation oncology community regarding its efficacy and safety.

Fifteen years ago a handful of researchers began investigating stereotactic body radiation therapy (SBRT) for low- and medium-risk prostate cancer.  The basis for the research was a theoretical radiobiological advantage.1 This was followed by a handful of studies with short followup.2-6  (Interestingly, fifteen years earlier, without the benefit of modern imaging or treatment technology, a small pioneering study by Lloyd-Davies in Urology7 showed the convenience benefit of fewer fractions at higher doses in a long-term 22-year study with good clinical results). But in the mid 2000s, most were skeptical—convinced that the very high fractional doses would result in unacceptably high long-term GI (rectal) and GU (urinary) toxicities.  They had no data either way to assess SBRT’s long term effectiveness in the treatment of prostate cancer.  

This article is part one of three. The others are:

2019 Papers Summarize Decades of Data from Thousands of Cancer Patients
Now, some 15 years later, three papers8,9,10  published during 2019 have summarized decades of data from thousands of prostate cancer patients, providing convincing evidence that SBRT is highly effective in disease control with low long-term toxicity, equivalent to that of conventional RT treatments.  In short, the data is in and the news is great for patients!

Amar Kishan, MD, chief of genitourinary oncology services in the Department Of Radiation Oncology at UCLA, has seen and documented such results. A paper that was published in JAMA (Journal of the American Medical Association) in February 2019, for which Dr. Kishan served as lead author, assessed long-term outcomes after SBRT for low-risk and intermediate-risk prostate cancer, following the outcomes of 2142 patients.  The study concluded that prostate SBRT "for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control.” This further "suggests that SBRT is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.” 8

Another paper, published five months later in the International Journal of Radiation Oncology, Biology & Physics (RED journal), reported on an impressive 6116 patients, analyzing survival rates, toxicity, and outcomes after prostate SBRT. Results showed a 7-year biochemical disease-free survival rate of 93.7 percent. They concluded that Prostate SBRT "has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority.” This is based on "substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity.”9

Regarding treatment effectiveness and durability, a third paper published in the RED journal in November 2019 showed how prostate SBRT eliminates evidence of disease as defined by decreasing PSA to normal levels. "In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs (PSA nadirs = low values). In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure." A figure within this paper shows the median PSA to be in the range of 0.2 ng/ml at 7 years post treatment. 10

When faced with a diagnosis of localized prostate cancer, patients can now comfortably add SBRT as a treatment option.  By adding SBRT to other options (surgery, traditional external beam radiation therapy, brachytherapy, focal ablative therapies & active surveillance), patients now have another choice that is both highly effective and efficient, with minimal short- and long-term toxicities.

Radiosurgery (SRS) and SBRT, also known as stereotactic ablative radiotherapy (SABR), are already being used to treat brain tumors and other brain disorders, lung cancer, liver cancer and in some clinics for prostate cancer treatment. Based on a 2018 review of multiple published studies, a panel of experts representing the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Urological Association gave moderate hypofractionation an official thumbs up.11,12  Importantly, SBRT Prostate has made it into NCCN guidelines.14  The 2019 papers show that the adoption of prostate SBRT continues to grow.

A Mulitinstitutional Study Shows Excellent Results with Gantry-Based C-Arm SBRT for Prostate Cancer
More recently a fourth study, now in press in the ASTRO journal Advances in Radiation Oncology (ARO), examines data for almost 1,000 patients across seven institutions delivered specifically with gantry-based C-Arm SBRT using volumetric arc treatment (RapidArc® treatment).  Earlier published data on SBRT for prostate cancer were from studies of patients treated either exclusively on robotic arm-mounted linear accelerators, which require long treatment times2,6 compared to RapidArc techniques, or on a combination of robotic arm and C-arm linac systems.  These are the first large-scale, long-term C-arm data. 

"In the most recent research data, severe acute and late toxicities were very rare, affecting less than one percent of patients three years after the treatment," says Prof. Marta Scorsetti, associate professor in diagnostic imaging and radiotherapy and director of the post-graduate school of radiation oncology at Humanitas University in Milan, Italy, one of the seven institutions involved in the study. "Moreover, the data suggest prostate SBRT allows an optimal disease control, with about 99 percent of biochemical control in low risk disease and 95 percent in intermediate risk disease." The paper's data reflect a mean follow-up of 3.1 years (0.5-10.8 range) and mirror other longer term results.13

"Mounting evidence indicates prostate SBRT is an excellent option, and we now understand that prostate cancer responds well to a higher dose per treatment and that these treatments are safe overall," Kishan explains. "We’ve seen a significant increase in the number of patients at our clinic who would prefer to be treated with SBRT in four or five short sessions, rather than 40+ sessions of conventional radiation therapy.” 

As long-term data continues to emerge on the safety and effectiveness of SBRT, advances in linac-based treatment delivery technologies and diagnostic, planning, and staging tools continue to make this treatment modality more attractive to clinicians in busy cancer centers. 

“SBRT is still in the minority of radiation treatments but the mounting data suggests it has the potential to become the standard of care across all cancer clinics,” Kishan concludes. “It’s effective without being invasive and shows minimal side effects. As a community, we owe it to our patients to increase awareness of the safety of SBRT and make it more widely available.”

It is particularly important to note that the most recent paper in press debunks the myth in some circles that only robotically mounted linear accelerators can effectively deliver prostate SABR/SBRT. This work emphasized in particular that “gantry-mounted prostate SBRT appears to be safe and effective in a multi-institutional setting. Thus, prostate SBRT is not anchored to any particular treatment platform,” the authors assert.

In short, prostate SBRT is here to stay regardless of the treatment modality. And it will become more important in an era of bundled care. As noted in a recent ASTRO blog by Spratt & Mitin: “We anticipate it [prostate SBRT] will only become increasingly utilized in the U.S. given the convergence of prospective and new level one evidence and financial incentives from the new bundled payment model. We anticipate that learning to safely deliver prostate SBRT will become very important in the not too distant future.” 14   

Linac-based SBRT for Prostate: Becoming a Standard Option at UCLA
Halcyon takes Northwest Community Healthcare to the leading edge of prostate SBRT

Additional information on Prostate SBRT can be found at: 
Webinars (Please use Internet Explorer)
WEBINAR: Stereotactic Body Radiotherapy (SBRT) for Prostate Cancer; Christopher King, MD, PhD, UCLA – October 2, 2013  

Videos (Please use Internet Explorer)
Margin Reduction with New Technologies for Prostate: Conventional Fx to SBRT: Daniel Hamstra, MD, PhD | University of Michigan | Ann Arbor, MI: in Radiosurgery Society Meeting May 7, 2014, Minneapolis, MN
Calypso® for Prostate: Our Edge in Treating Prostate SABR Treatments: Connie Mantz, MD | 21st Century Oncology | Fort Myers, FL: in Radiosurgery Society Meeting May 7, 2014, Minneapolis, MN
Gantry-Based Prostate Radiosurgery Outcomes: Amar Kishan, MD, University of California - Los Angeles, Los Angeles, CA: in : in Radiosurgery Society Meeting March 20, 2019, San Diego, CA

References: 
1.    King CR, Fowler JF. A simple analytic derivation suggests that prostate cancer alpha/beta ratio is low. Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):213-4. 
2.    King CR, Lehmann J, Adler JR, Hai J. CyberKnife radiotherapy for localized prostate cancer: rationale and technical feasibility. Technol Cancer Res Treat. 2003 Feb;2(1):25-30.
3.    Madsen BL, Hsi RA, Pham HT, Presser J, Esagui L, Corman J, Myers L, Jones D. Intrafractional stability of the prostate using a stereotactic radiotherapy technique. Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1285-91.
4.    Madsen BL, Hsi RA, Pham HT, Fowler JF, Esagui L, Corman J. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):1099-105.
5.    Pawlicki T, Cotrutz C, King C. Prostate cancer therapy with stereotactic body radiation therapy. Front Radiat Ther Oncol. 2007;40:395-406.
6.    King CR, Brooks JD, Gill H, Pawlicki T, Cotrutz C, Presti JC Jr. Stereotactic body radiotherapy for localized prostate cancer: interim results of a prospective phase II clinical trial. Int J Radiat Oncol Biol Phys. 2009 Mar 15;73(4):1043-8
7.    Lloyd-Davies RW, Collins CD, Swan AV. Carcinoma of prostate treated by radical external beam radiotherapy using hypofractionation. Twenty-two years' experience (1962-1984). Urology. 1990 Aug;36(2):107-11.
8.    Kishan AU, Dang A, Katz AJ, Mantz CA, Collins SP, Aghdam N, Chu FI, Kaplan ID, Appelbaum L, Fuller DB, Meier RM, Loblaw DA, Cheung P, Pham HT, Shaverdian N, Jiang N, Yuan Y, Bagshaw H, Prionas N, Buyyounouski MK, Spratt DE, Linson PW, Hong RL, Nickols NG, Steinberg ML, Kupelian PA, King CR. Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer. JAMA Netw Open. 2019 Feb 1;2(2):e188006
9.    Jackson WC, Silva J, Hartman HE, Dess RT, Kishan AU, Beeler WH, Gharzai LA, Jaworski EM, Mehra R, Hearn JWD, Morgan TM, Salami SS, Cooperberg MR, Mahal BA, Soni PD, Kaffenberger S, Nguyen PL, Desai N, Feng FY, Zumsteg ZS, Spratt DE. Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies. Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):778-789
10.    Jiang NY, Dang AT, Yuan Y, Chu FI, Shabsovich D, King CR, Collins SP, Aghdam N, Suy S, Mantz CA, Miszczyk L, Napieralska A, Namysl-Kaletka A, Bagshaw H, Prionas N, Buyyounouski MK, Jackson WC, Spratt DE, Nickols NG, Steinberg ML, Kupelian PA, Kishan AU. Multi-Institutional Analysis of Prostate-Specific Antigen Kinetics After Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys. 2019 Nov 1;105(3):628-636.
11.    Morgan SC, Hoffman K, Loblaw DA, Buyyounouski MK, Patton C, Barocas D, Bentzen S, Chang M, Efstathiou J, Greany P, Halvorsen P, Koontz BF, Lawton C, Leyrer CM, Lin D, Ray M, Sandler H. Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline. Pract Radiat Oncol. 2018 Nov - Dec;8(6):354-360. 
12.    ASTRO/ASCO/AUA Guideline on Hypofractionation for Localized Prostate Cancer, November 2018 (Web posted: October 2018) 
13.    Dang AT, Levin-Epstein RG, Shabsovich D, Cao M, King CR, Chu FI, Mantz CA, Stephans KL, Reddy CA, Loblaw DA, Cheung P, Scorsetti M, Cozzi L,  DeNittis AS, Wang Y, Zaorsky N, Nickols NG, Kupelian PA, Steinberg ML, Kishan AU.  Gantry-Mounted Linear Accelerator–Based Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer Advances in Radiation Oncol 2019 Oct 14 in press 
14.    https://www.nccn.org/professionals/physician_gls/default.aspx#prostate updated August 19, 2019
15.    Daniel Spratt, MD, and Timur Mitin, MD, PhD, The Future of Prostate Radiation Therapy in the Era of Bundled Payment: Less is more? ASTRO Blog; Posted: December 3, 2019.



The information captured herein represents the genuine experience of the attributed individuals and may not necessarily represent the views of Varian or the above referenced institution. Individuals were not compensated for their participation. Radiation treatment may not be appropriate for all cancers. Individual results may vary.