Clinical investigation: prostate
Improvement in relapse-free survival throughout the PSA era in patients with localized prostate cancer treated with definitive radiotherapy: Year of treatment an independent predictor of outcome

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Abstract

Purpose

In patients treated with radical prostatectomy in the prostate-specific antigen (PSA) era, it has been demonstrated that the year of treatment in the PSA era is associated with better pathologic parameters and outcomes, independently of other well-recognized parameters such as clinical stage, pretreatment PSA level, or Gleason score. The purpose of the present study was to study a similar phenomenon with definitive radiotherapy (RT).

Methods and materials

The inclusion criteria were as follows: clinical Stage T1–T2, available pretreatment PSA level and biopsy Gleason score, treatment delivered before January 2000 with standard fractionation external beam radiotherapy to at least 70 Gy, no adjuvant androgen deprivation (AD), all neoadjuvant AD limited to ≤6 months, and a minimum of 3 years of PSA follow-up. A total of 467 cases treated between January 1986 and December 1999 were included. Short-course AD in the adjuvant or neoadjuvant setting for ≤6 months was given in 124 cases (27%). The median radiation dose was 74 Gy (range 70.0–78.0). A conformal technique was used in 293 cases (63%). The median follow-up was 62 months (range 37–189). A total of 4931 follow-up PSA levels were available for analysis (average 11 per patient). A multivariate analysis for factors affecting biochemical relapse-free survival rates using the proportional hazards model was performed for all cases using the following variables: age (continuous variable), race (black vs. white), clinical T stage (T1–T2a vs. T2b–T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), use of AD (yes vs. no), radiation dose (continuous variable), and year of treatment (continuous variable: 1986–1999).

Results

The projected 8-year biochemical relapse-free survival rate was 74%. The projected 5-year biochemical relapse-free survival rate for the 143 patients treated in the 1986–1995 period was 58% vs. 82% for the 324 patients treated in the 1996–1999 period (p <0.001). The difference was attributable to a multitude of factors (earlier stage cancer, higher radiation doses, shorter follow-up). To study the confounding effects of these factors on the year of therapy, a multivariate analysis was performed. The multivariate analysis revealed the initial PSA level (p <0.001), Gleason score (p <0.001), RT dose (p = 0.045), and year of treatment (p <0.001) to be independent predictors of outcome. Age (p = 0.41), race (p = 0.14), T stage (p = 0.10), and use of AD (p = 0.58) were not.

Conclusion

When controlling for tumor, treatment, and follow-up parameters, the year in which RT was performed was still an independent predictor of outcome, consistent with observations made for radical prostatectomy patients. This indicates a more favorable presentation of localized prostate in current years probably related to a combination of factors such as screening and increased patient awareness leading to earlier diagnosis. Outcome predictions should be based on contemporaneous series.

Introduction

During the past 10–15 years, a significant stage migration toward more favorable presentations has occurred. Most of this stage migration has been attributed to prostate-specific antigen (PSA) screening. However, in patients treated with radical prostatectomy, a steady decrease in the extracapsular extension rates has occurred independent of the presentation PSA level, biopsy Gleason score, and clinical stage (1). This would indicate a stage migration that is occurring in conjunction with PSA screening. Better relapse-free survival rates have also been reported in different eras for radical prostatectomy patients, with the year of therapy an independent predictor of relapse (2). This has led to an update of the Partin tables predicting pathologic outcomes, with observations made on contemporary patients rather than patients from prior eras (3). In the current study, we attempted to demonstrate a similar phenomenon of outcomes improving during the years in the PSA era, independent of other well-known prognosticators.

Section snippets

Methods and materials

A total of 1276 patients were treated with external beam radiotherapy (EBRT) for adenocarcinoma of the prostate at the Cleveland Clinic Foundation between 1986 and 1999. To include the most homogeneous group possible, with the longest follow-up possible, the following cases were excluded: patients receiving <70 Gy total radiation dose (n = 386), clinical Stage T3 disease (n = 101), no available pretreatment PSA level (n = 2), no available biopsy Gleason score (n = 11), patients receiving

Results

Table 1 summarizes the pretreatment clinical and treatment characteristics of the 467 patients. The median age was 68 years (range 46–82). Clinical T stages were significantly lower in the more recent years. The median iPSA level was 8.6 ng/mL (range 1.0–150.0). Although trends in PSA distributions could be seen, these were not significantly different statistically between the earlier and later periods. Similarly, no differences were found in the biopsy Gleason scores.

The projected 5- and

Discussion

During the past 10–15 years, significant stage migration toward more favorable presentations has occurred. Most of this stage migration has been attributed to PSA screening 7, 8. However, in patients treated with radical prostatectomy, a steady decrease in ECE rates has occurred, independent of presentation PSA level, biopsy Gleason score, and clinical stage (1). This would indicate a stage migration that is occurring in conjunction with PSA screening. Better relapse-free survival rates have

Conclusion

When controlling for tumor and treatment parameters, the year in which RT was performed was still an independent predictor of outcome. This is consistent with observations made for radical prostatectomy patients. A more favorable presentation of localized prostate cancer seen in current years in conjunction with PSA screening is possibly related to changing cancer biology, but more probably to increased physician and patient awareness, leading to more aggressive biopsies detecting earlier

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