External beam radiotherapy versus radical prostatectomy for clinical stage T1-2 prostate cancer: therapeutic implications of stratification by pretreatment PSA levels and biopsy Gleason scores

Cancer J Sci Am. 1997 Mar-Apr;3(2):78-87.

Abstract

Purpose: Prostate-specific antigen (PSA) has affected the management of prostate cancer by allowing better case selection. The comparison between the two definitive treatment modalities, radiotherapy (RT) and radical prostatectomy (RP), can now be made accurately with respect to case selection and treatment outcome.

Patients and methods: The charts of 787 patients with prostate carcinoma who were treated with either RP alone or RT alone between 1987 and 1993 were reviewed. Patients with stage T3 disease, without pretreatment PSA levels or biopsy Gleason scores (GS), with synchronous bladder cancers or receiving adjuvant therapy, were excluded. Patients with less than 2 years' follow-up were also excluded. Of the remaining 551 patients, 253 were treated with RT and 298 with RP. The median pretreatment PSA level for RP patients was 8.1 versus 12.1 for the RT patients. The median radiation dose was 68.4 Gy. Positive margins were reported in 49% after RP. The median follow-up time was 42 months (range: 24 to 108).

Results: For the 551 patients, the 5-year biochemical relapse-free survival (bRFS) rate was 53%, with biochemical relapse being defined as either a detectable PSA level after RP, or two consecutive rising PSA levels after RT. All clinical relapses were associated with rising PSA levels. The 5-year bRFS rates for RT versus RP were 43% versus 57%, respectively. Multivariate time-to-failure analysis using the proportional hazards model for clinical parameters showed pretreatment PSA level and biopsy Gleason scores to be the only independent predictors of relapse. Clinical stage and treatment modality were not independent predictors of failure. Using PSA and GS, two risk groups were defined: low risk (PSA < or = 10.0 and GS < or = 6) and high risk (PSA > 10.0 or GS > or = 7). The 5-year RFS rates for the low-versus high-risk groups were 81% versus 34%, respectively. Forty-eight percent of RP patients were low-risk cases versus 33% of RT patients. The rate of surgical margin involvement in RP patients was 39% in the low-risk group versus 59% in the high-risk group. For low-risk patients, the 5-year RFS rates for patients treated with RT versus RP were 81% versus 80%, respectively. In this subgroup, the bRFS rates for patients with negative margins were identical to the bRFS rates of patients treated with radiotherapy. However, patients with positive surgical margins fared significantly worse. For high-risk patients, the 5-year RFS rates for patients treated with RT versus RP were 26% versus 37%, respectively. In this subgroup, there was a definite advantage to surgery if negative margins were achieved: 5-year bRFS 62%, compared to 26% for RT and 21% for surgery with positive margins.

Conclusions: By using biochemical failure as an endpoint, more failures are documented after RP or RT than previously suspected. However, case selection using pretreatment PSA levels and biopsy GS can result in large differences in control rates. Significantly more high-risk patients are treated with RT. By stratifying cases using PSA and biopsy GS, treatment outcome is equivalent after either radiotherapy or surgery. Further follow-up is needed to confirm these findings after 5 years. For low-risk cases, there is no difference between radiotherapy and surgery, even when negative margins are achieved. Positive surgical margins predict for poor outcome even in low-risk cases. Standard radiotherapy alone should not be used for lesions with aggressive features. The outcome in high-risk cases is better with surgery if negative margins are achieved. For such high-risk patients, several new treatment approaches are currently being investigated with either high-dose conformal radiotherapy with or without androgen blockade, or neoadjuvant androgen blockade or radical prostatectomy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Disease-Free Survival
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging / methods
  • Prostate-Specific Antigen / blood
  • Prostatectomy*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / surgery*
  • Recurrence
  • Salvage Therapy

Substances

  • Prostate-Specific Antigen