Efficacy of external beam radiotherapy compared to permanent prostate implant in treating low risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and PSA

Abstract

Recent studies suggest that treatment of low risk prostate cancer yields similar results for patients treated with external beam radiation therapy (EBRT) to greater than 72 Gy or permanent prostate implant (PPI). These studies usually define outcome based on the ASTRO consensus definition. Unfortunately, the ASTRO definition has a relatively poor sensitivity (0.61) and has not been validated for patients treated with PPI. We have previously shown that magnetic resonance spectroscopic imaging (MRSI) findings, when used in conjunction with PSA and confirmed by biopsies, may provide a useful tool for post treatment outcomes of prostate patients. The objective of this study was to evaluate the metabolic response of the prostate by comparing the time to resolution of disease (TRD), time to complete metabolic atrophy (CMA), and the magnitude of the PSA response or nadir (nPSA) between low risk patients treated with EBRT and PPI. Twenty-five patients treated with EBRT and 25 treated with PPI had MRSI examinations prior to and/or at various times following therapy. All patients were considered low risk, with Gleason scores equal to 6, pretreatment PSA values less than or equal to 10, and stage T1 or T2. The patients were grouped by treatment type (EBRT or PPI) with the median prescribed dose of 72 Gy (range 68 to 75.6) and 144 Gy, respectively. The spectra from all usable voxels within the prostate were examined for detectable levels of metabolic signal and the percent of voxels in each category were tabulated as atrophic, cancerous or healthy. The TRD and the time to nPSA were compared. Additionally, the biological equivalent dose (BED) was calculated for each PPI patient to evaluate the efficacy of the delivered dose relative to the resolution of disease determined by MRSI. The mean TRD was 25.8 and 32.2 months with a mean time to nPSA of 38.4 and 45.9 months for PPI and EBRT patients, respectively. Over time our results suggest a gradual increase in atrophy, and a consistent decline in cancerous metabolism. Ninety percent of the patients treated with EBRT obtained a (-) post treatment MRSI, while 10% had a (+) MRSI. Twenty percent of these patients achieved CMA. All 25 PPI patients had (-) MRSI studies with 86% achieving CMA. The higher prescribed dose delivered for PPI (144 Gy) vs. EBRT (72 Gy) also resulted in a median PSA of 0.2 ng/ml (range 0.01 to 1.0) and .94 ng/ml (range 0.02 to 7.1) after PPI vs. EBRT, respectively. BED resulted in a median dose of 146 Gy to the entire prostate gland and 219 Gy to the MRSI (or biopsy) defined cancer. This study strongly suggests that metabolic and biochemical responses (TRD, CMA, and nPSA) of the prostate to 144 Gy, delivered by PPI, is significantly more pronounced than after a dose of 72 Gy delivered by EBRT. This study does not prove that PPI is more effective at curing prostate cancer than EBRT but demonstrates that PPI is more effective at destroying prostate metabolism. This study also raises questions about alpha/beta ratio calculations based on the assumption that EBRT and PPI are equal in terms of their biologic impact on prostate tissues