Stereotactic Body Radiation Therapy Versus Intensity-Modulated Radiation Therapy for Prostate Cancer: Less Cost at the Expense of More Genitourinary Toxicity Is a Concerning But Testable Hypothesis

Abstract

Whilerandomizedcontrolledtrials(RCTs) showthatprostatespecific antigen (PSA) –based screening reduces death from prostate cancer (PC) and this effect appears to be more pronounced in younger and presumably healthier men (number needed to treat of 12 at a median follow-up of 14 years), the US Preventative Task Force has concluded that screening for PC with PSA does more harm than good. Why? While it has been suggested in one RCT (Prostate Cancer Intervention Versus Observation Trial [PIVOT]) after a median follow-up of 10 years that treatment of low-risk PC, which is detected more often with PSA screening, does not lead to a reduction in death from PC, the treatment effect for all men in the study approached significance (P .09) in reducing death from PC. This was observed despite being underpowered (designed to accrue 2,000 but accrued only 731) and enrolling men of less than average health based on a comparative SEER program study. Therefore, should these results at a 10-year median follow-up be used to decide on treatment for healthy men whose remaining life expectancy is greater than 10 years? Probably not, yet this data has been used to deter PSA screening and has prompted active surveillance in men diagnosed with low-risk PC who are healthier than men in PIVOT. While screening for and subsequent treatment of PC in men with limited life expectancy due to comorbidity has led some men to experience treatment-related toxicity without expectation of avoiding metastasis and death from PC termed “over diagnosis and overtreatment” respectively; is this a reason to abandon PSA screening altogether? The concern is that not screening high-risk patients, such as healthy African American men who are at higher risk of harboring and dying from aggressive PC compared with other races and ethnicities, might lead to more advanced disease that is less amenable to cure. We know that these advanced cancers are less likely to be cured despite multimodality therapies which are more toxic then unimodality therapy, which is often curative when the disease is PSA detected. Moreover, is this a reason to tell an otherwise healthy man who has been diagnosed with “low risk PC” that he does not need treatment when, due to prostate needle biopsy sampling error, 25% of men with biopsy proven “low-risk PC” are found to have at least intermediate risk PC after undergoing radical prostatectomy (RP) and when for such men PIVOT suggested a reduction in death from PC when RP was offered? The unfortunate result of these claims regarding screening for and treatment of PC is that some men facing a diagnosis of PC are requesting de-escalation of, or no immediate treatment for, their PC in an effort to avoid the possibility of experiencing toxicity without clinical benefit or overtreatment. To that end, treatments such as focal ablation and shortened (or accelerated) courses of radiation therapy using cyberknife or stereotactic body radiation therapy (SBRT) are being studied, however randomized evidence of comparable toxicity and efficacy compared with accepted standard of practice are currently unavailable. Of concern, while only a theoretical basis for improved local control with accelerated radiation treatment exists, this approach is being used to treat men with PC off study. It is possible this treatment could be less efficacious and more toxic then current standards of care. Fortunately, data are currently pending from an ongoing Swedish RCT (International Standard Randomized Controlled Trial Number Register 45905321) evaluating the relative efficacy and toxicity of an accelerated RT regiment with high-dose intensity-modulated radiation therapy (IMRT) which is a standard of care as endorsed by the 2013 National Cancer Center Network guidelines. Specifically the two randomized treatment arms are 78 Gy in 39 conventional 2 Gy IMRT treatments over 8 weeks versus 42.7 Gy in seven hypofractionated or accelerated 6.1 Gy SBRT treatments over 2.5 weeks for primarily intermediate-risk PC. Importantly, toxicity reporting from this RCT is expected by 2015. While awaiting the results of this RCT, the study by Yu et al that accompanies this editorial evaluates the relative toxicity of these two approaches. They used the Chronic Condition Warehouse database, which is a comprehensive database of 100% of Medicare fee-forservice claims for patients with specific conditions such as PC. They then performed a 2:1 match (IMRT to SBRT) within each follow-up JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 12 APRIL 2