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Interstitial Brachytherapy Should Be Standard of Care for Treatment of High-Risk Prostate Cancer

Interstitial Brachytherapy Should Be Standard of Care for Treatment of High-Risk Prostate Cancer

ABSTRACT: High-risk prostate cancer represents a therapeutic challenge for both the urologist and radiation oncologist. Biochemical outcomes with radical prostatectomy and external-beam radiation therapy are poor in this subset of patients. These unfavorable results have led some to believe that high-risk prostate cancer is not curable with conventional treatment approaches, which has been an impetus for many of the current trials using neoadjuvant chemotherapy and prostatectomy. With the established efficacy of interstitial brachytherapy, these efforts are likely excessive. Most modern trials indicate excellent biochemical control rates among high-risk patients treated with an aggressive locoregional approach that includes brachytherapy. A thoughtful review of the literature would suggest that interstitial brachytherapy offers a therapeutic advantage over other local treatment modalities and should be considered standard treatment for aggressive organ-confined prostate cancer.

Given the poor outcomes observed with radical prostatectomy (RP) and external-beam radiation therapy (EBRT), some in the urologic community contend that high-risk disease is not curable with currently available treatment strategies.[1,2] In fact, there is a growing contingent of clinicians who advocate the use of chemotherapy in conjunction with RP. With the established efficacy of brachytherapy, these efforts are likely excessive.

Long-term outcomes data now demonstrate excellent biochemical control rates among low- and intermediate-risk patients treated with interstitial brachytherapy.[3-6] Traditionally, there has been less enthusiasm for the use of brachytherapy in the setting of high-risk disease.[7] This relates in large part to historical data suggesting suboptimal outcomes among high-risk patients treated with brachytherapy.[8-10] These studies are limited by their inadequate reporting of implant dosimetry and lack of planned treatment margins. Indeed, most modern trials show exceptional biochemical control rates among high-risk patients treated with a regimen that includes brachytherapy.[11-16]

Adverse pathologic features, which are characteristic of high-risk disease, correlate with a higher likelihood of extraprostatic extension and seminal vesicle involvement.[17] This has led to the perception that patients with high-risk features may not be adequately treated with brachytherapy.[7,18,19] On the contrary, modern implant technique allows for generous extracapsular margins and treatment of the proximal seminal vesicles, with the added benefit of intraprostatic dose escalation. For these reasons, brachytherapy offers a unique advantage over other local therapies and is actually ideally suited for patients with the most aggressive local biology.

Several risk stratification systems have been developed. Nearly all are based on the premise that serum prostate-specific antigen (PSA), clinical T stage, and Gleason score are independent predictors of biochemical failure–free survival.[20-22] Perhaps most popular is the D'Amico system, which categorizes patients as low-risk (Gleason ≤ 6, PSA ≤ 10 ng/mL and stage T2a or less), intermediate-risk (Gleason 7, PSA 10–20 ng/mL, and/or stage T2b), or high-risk (Gleason 8–10, PSA > 20 ng/mL, and/or stage T2c or higher).[8] In recent years, percent positive biopsies has also been identified as an independent predictor of biochemical outcome.[23-26]

Herein, we attempt to dispel some common misconceptions about prostate brachytherapy, and as a secondary objective, compare clinical outcomes with different treatment modalities. In doing so, we hope to convince the reader that brachytherapy is the best available local therapy and should be standard of care in the treatment of high-risk prostate cancer.

Risk of Extracapsular Extension

Early data published by D'Amico and others suggested better biochemical control rates among intermediate- and high-risk prostate cancer patients treated with RP or EBRT, as compared to those undergoing interstitial implant.[8-10] D'Amico's study, completed nearly a decade ago, continues to be cited as an argument against the use of brachytherapy in the setting of intermediate- and high-risk disease.

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