Implementation Date: April 2015 Clinical Operations



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National Imaging Associates, Inc. Clinical guideline PROSTATE CANCER Original Date: March 2011 Page 1 of 5 Radiation Oncology Last Review Date: March 2015 Guideline Number: NIA_CG_124 Last Revised Date: April 2015 Responsible Department: Implementation Date: April 2015 Clinical Operations INTRODUCTION: Prostate cancer is diagnosed by biopsy and evaluated (staged) to determine extent of disease (local, regional, or distant metastatic). Both surgery and radiation therapy is used to treat prostate cancers that are organ-confined or extend into tissues adjacent to the prostate. Patients with very low/low risk disease should be considered for active surveillance. Patients with intermediate risk disease may be considered for short course (4-6 months) of neoadjuvant/concomitant/adjuvant ADT. Daily prostate localization can be accomplished with imaging modalities, e.g., ultrasound images, computed tomography (CT) images, or implanted fiducial markers, incorporated into an image guided radiation therapy (IGRT) system. Patients with high risk disease may be considered for pelvic lymph node irradiation and 2-3 years of neoadjuvant/adjuvant ADT. INDICATIONS FOR RADIATION THERAPY AND TREATMENT OPTIONS Very Low Recurrence Risk (Primary Tumor Stage [T] is T1c, PSA <10 ng/ml, and Gleason score 6, PSA density <0.15ng/nl per g, < 3biopsy cores positive with < 50% cancer in each) Active surveillance (discussed with patient as treatment option) o Highly conformal radiation therapy technique (3D-CRT/IMRT) doses 75 79.2 Gy (up to 44 fractions) with IGRT LDR Brachytherapy Low Recurrence Risk (Primary Tumor Stage [T] is T1-T2a, PSA <10 ng/ml, and Gleason score 6) Active surveillance (discussed with patient as treatment option) o Highly conformal radiation therapy technique (3D-CRT/IMRT) doses 75 79.2 Gy (up to 44 fractions) with IGRT o SBRT delivered at five fractions or less at 6.5 Gy per fraction or greater. Appropriate as a standalone radiation modality and not as a boost to other conventional methods of radiation treatment. LDR Brachytherapy Intermediate Recurrence Risk (Primary Tumor Stage [T] T2b-T2c or PSA 10-20 ng/ml or Gleason score 7) o Highly conformal radiation therapy technique (3D-CRT/IMRT) doses 75 81 Gy (up to 45 fractions) 1 RadOnc Prostate Cancer

o SBRT delivered at five fractions or less at 6.5 Gy per fraction or greater. Appropriate as a standalone radiation modality and NOT as a boost to other conventional methods of radiation treatment. Brachytherapy (LDR/HDR) boost combined with EBRT after 40-50 Gy) High Recurrence Risk (Primary Tumor Stage [T] T3a or PSA >20 ng/nl or Gleason score 8, or two or more intermediate risk factors) o Highly conformal radiation therapy technique (3D-CRT/IMRT) doses 78 81 Gy Very High Recurrence Risk (Primary Tumor Stage [T] T3b-T4) without Metastasis o Highly conformal radiation therapy technique (3D-CRT/IMRT) doses 78-81 Gy Brachytherapy (LDR/HDR) boost combined with EBRT after 40-50 Gy Radiation Therapy for Patients with Locally Advanced or Metastatic Prostate (T3b T4, or any T and N1 disease) o Highly conformal radiation therapy technique (3D-CRT/IMRT) Doses 78-81 Gy Post-Prostatectomy One of the following must be met: o Detectable PSA or initially undetectable PSA, but with recent detectable and rising values on 2 or more measurements with no evidence of metastatic disease o Positive margins o Seminal vesicle invasion o Extracapsular extension o Highly conformal radiation therapy technique (3D-CRT/IMRT) Doses 64 72 Gy (up to 40 fractions) with IGRT TREATMENT OPTIONS REQUIRING PHYSICIAN REVIEW: The radiation treatment options below require review by a physician reviewer and may include deliberation on whether or not active surveillance and surgery have been considered prior to the decision to request radiation therapy: Brachytherapy alone (monotherapy) may be approved for Intermediate Recurrence Risk (Primary Tumor Stage [T] T2b-T2c or PSA 10-20 ng/ml or Gleason score 7) upon review with a physician reviewer. Brachytherapy alone is not considered appropriate if the patient has multiple intermediate risk factors and is thus higher risk. Studies comparing HDR brachytherapy as monotherapy have not shown clinical outcomes to be superior to conventional radiation therapy. Medical record documentation should include the medical rationale and necessity for performing HDR 2 RadOnc Prostate Cancer

Brachytherapy rather than LDR brachytherapy, 3D conformal or IMRT. Proton beam is not an approved treatment option for localized prostate cancer. Studies comparing proton beam therapy alone to 3-D conformal radiation or IMRT are limited. Overall, studies have not shown clinical outcomes to be superior to conventional radiation therapy. For peer review purposes supporting documentation from the radiation oncologist is required and should include the clinical rationale for performing proton beam rather than 3-D conformal or IMRT. 3 RadOnc Prostate Cancer

REFERENCES Abdel-Wahab M, Mahmoud O, Merrick G, et al. Expert Panel on Radiation Oncology- Prostate. ACR Appropriateness Criteria External Beam Radiation Therapy Treatment Planning for Clinically Localized Prostate Cancer. [online publication]. Reston (VA): American College of Radiology (ACR); 2011.Available at: http://guideline.gov/content.aspx?f=rss&id=35164. Accessed on April 22, 2014. American Society of Therapeutic Radiation Oncology (ASTRO). Choosing Wisely Released September 23, 2013 (1-5) and September 15, 2014 (6-10) Retrieved February 24, 2015 from: http://www.choosingwisely.org/doctor-patientlists/american-society-for-radiation-oncology/ American Society of Therapeutic Radiation Oncology (ASTRO). Stereotactic Body Radiation Therapy (SBRT). Updated 4-17-13. Retrieved February 27, 2015 from: https://www.astro.org/uploadedfiles/main_site/practice_management/reimbursement/2 013HPcoding%20guidelines_SBRT_Final.pdf Hummel S, Simpson EL, Hemingway P, Stevenson MD, Rees A. Intensity-modulated radiotherapy for the treatment of prostate cancer: A systematic review and economic evaluation. Health Technol Assess. 2010; 14 (47):1-108, iii-iv. Institute of Cancer Research, United Kingdom. Intensity-Modulated Radiation Therapy in Treating Patients with Localized Prostate Cancer. NCT00392535. Last updated May 19, 2011. Available at: http://clinicaltrials.gov/ct2/show/nct00392535?term=imrt&recr=open&type=intr&pha se=12&rank=28 Clark EE, Thielke A, Kriz H, et al. Intensity modulated radiation therapy. Final Evidence Report. Prepared by the Oregon Health & Science University, Center for Evidencebased Policy for the Washington State Health Care Authority, Health Technology Assessment Program. Olympia, WA: Washington State Health Care Authority, Health Technology Assessment Program; August 20, 2012. Available at: http://www.hca.wa.gov/hta/pages/intensity_radiation.aspx. Freeman DE, et al: Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes. Radiat Oncol. 2011 Jan 10;6:3. Kang JK et al: Image-guided stereotactic body radiation therapy for localized prostate cancer. Tumori. 2011 Jan-Feb;97(1):43-8. Katz AJ. CyberKnife Radiosurgery for Prostate Cancer. Technol Cancer Res Treat. 2010 Oct; 9(5):463-472. Accessed November 14,2014. http://www.tcrt.org/c4304/c4309/cyberknife-radiosurgery-for-prostate-cancer-463-472- p17811.html Katz AJ, Santoro M. Quality of life and efficacy for stereotactic body radiotherapy for treatment of organ confined prostate cancer. Int JRadiat Oncol Biol Phys. 2010 Nov 1; 4 RadOnc Prostate Cancer

78(3):S58. Abstract 123. Accessed November 14, 2014. http://www.redjournal.org/article/s0360-3016(10)01143-0/fulltext King C. Stereotactic body radiotherapy for prostate cancer: current results of a phase II trial. Front Radiat Ther Oncol. 2011;43:428-37. Epub 2011 May 20. King CR et al: Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):877-82. Epub 2011 Feb 6. Michalski JM, Lawton C, El Naqa I, et al. Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2010; 76(2):361-368. http://www.astro.org/uploadedfiles/main_site/practice_management/reimbursement/a STRO%20PBT%20Model%20Policy%20FINAL.pdf. https://www.astro.org/uploadedfiles/main_site/practice_management/reimbursement/2 013HPcoding%20guidelines_SBRT_Final.pdf. Muacevic A, et al: Safety and feasibility of image-guided robotic radiosurgery for patients with limited bone metastases of prostate cancer. Urol Oncol. 2011 Apr 8. National Comprehensive Cancer Network (NCCN). Prostate Cancer Version 1.2015 Retrieved February 27, 2015 from: http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf Oermann EK, et al: Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer. J Hematol Oncol. 2011 Mar 27;4:12. Yu JB, et al: Proton versus Intensity-Modulated Radiotherapy for Prostate Cancer Patterns of Care and Early Toxicity, J Natl Cancer Inst. 2013;105(1):25-32. 5 RadOnc Prostate Cancer