What are outcomes of conventional external beam radiotherapy (EBRT) for the treatment of prostate cancer?

Updated: Nov 29, 2018
  • Author: Isamettin Andrew Aral, MD, MS; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

One of the major outcome determinants for clinically localized prostate cancer is tumor stage. Staging systems have always acknowledged the significance of extraglandular disease. In both the Whitmore classification schema and the tumor-node-metastasis (TNM) system, the presence of disease beyond the prostate (ie, stage C and stage T3, respectively) indicates a poor prognosis. This observation predates the use of modern prognostic variables associated with increased risk of extracapsular disease (ie, elevated PSA level and high Gleason score).

Although radiation therapy was used in the management of locally advanced lesions, the long-term results, even in the pre-PSA era, were relatively poor. Patients diagnosed with locally advanced disease (ie, stage C or T3 disease) who were treated with EBRT had acceptable disease-free survival (DFS) rates at 5 years, approaching 60%-65% in most series; however, 10-year DFS rates were less encouraging (30%-40%). At 15 years, failure rates continued to increase (70%-80%).

These results typify the experience gained through review of historical controls; however, they are significantly limited because of less sophisticated treatment techniques, lower total doses offered, and inadequacies of staging. Newer information continues to be generated by employing modern radiotherapy techniques and increasing therapy doses. Similarly, the rates of disease control are more carefully reported (eg, PSA-based outcome in lieu of clinical failure endpoints).

Patients undergoing definitive radiotherapy are typically considered to have achieved biochemical control of disease if the PSA level is not rising and the serum PSA level is below 0.5 ng/mL. Several definitions of biochemical failure have been proposed in the radiation oncology literature; however, 3 consecutive rises in the serum PSA level have been proposed as an accepted marker for failure in an American Society of Therapeutic Radiation Oncology (ASTRO) consensus conference.

Despite the increasing body of literature that considers PSA level a measurable determinant of treatment outcome, this tumor marker has been in wide use for a relatively short time. Before the adoption of PSA level as a marker, endpoints for clinical outcome were largely subjective and included prostate assessments based on clinical examination (eg, digital rectal examination [DRE]) and nonspecific serum markers (eg, alkaline phosphatase and acid phosphatase). The poor sensitivity of DRE has made this form of posttreatment assessment less and less useful.

As more studies use serum PSA level to assess treatment outcome, comparison with larger historic series (including those of the American College of Radiology’s Patterns of Care Studies) becomes harder. Several institutions have reported 5-year and 10-year PSA-based outcomes; however, the limited follow-up with posttreatment PSA studies and the protracted natural history of the disease make historical comparisons difficult. Unlike clinical outcomes, PSA-based outcomes suggest that long-term control can be difficult for locally advanced disease.

A study that examined the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer reported that dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. [16, 17]

A study that included 1,338 patients with lymph node metastasis after radical prostatectomy reported that adjuvant androgen deprivation therapy with external beam radiation therapy was associated with better overall survival that adjuvant androgen deprivation therapy or observation alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32-0.66, p<0.0001) or observation (HR: 0.41, 95% CI: 0.27-0.64, p<0.0001). The study also found that ten-year mortality risk difference between adjuvant androgen deprivation therapy with external beam radiation therapy, observation, or adjuvant androgen deprivation therapy alone ranged from 5% in low-risk patients to 40% in high-risk patients. [18]


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