title: Influence of local tumor control on distant metastases and cancer related mortality after external beam radiotherapy for prostate cancer.
abstract: OBJECTIVE
  We report local control outcomes, as assessed by posttreatment biopsies in patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer. In addition, we report the influence of local tumor control on long-term distant metastases and cause specific survival outcomes.
  
  
  METHODS
  Posttreatment prostate biopsies were performed in 339 patients who underwent 3-dimensional conformal radiotherapy for clinically localized prostate cancer. The histological outcome of prostate biopsy was classified as positive-prostatic adenocarcinoma without typical radiation induced changes or negative-no evidence of carcinoma or severe treatment effect. Median followup in this group of 339 patients was 10 years after the completion of treatment and 6.25 years after posttreatment biopsy.
  
  
  RESULTS
  Overall biopsy outcomes in these patients were positive in 32%, severe treatment effect in 21% and negative in 47%. A higher radiation dose in the intermediate and high risk subgroups was associated with a lower incidence of positive biopsy. Of patients at intermediate risk who received a dose of 75.6 or greater 24% had a positive biopsy compared to 42% who received 70.2 Gy or less (p = 0.03). In the high risk group positive treatment biopsies were noted in 51% of patients who received 70.2 Gy or less, 33% of those who received 75.6 Gy and 15% of those who received 81 Gy or greater (70.2 or less vs 75.6 Gy p = 0.07 and 75.6 vs 81 Gy or greater p = 0.05). Short course neoadjuvant androgen deprivation therapy before 3-dimensional conformal radiotherapy had a significant impact on the posttreatment biopsy outcome. Of patients who did not receive androgen deprivation therapy 42% had a positive biopsy compared to 16% who received androgen deprivation therapy (p <0.0001). Patients with negative and severe treatment effect biopsies had similar 10-year prostate specific antigen relapse-free survival outcomes that were markedly different from outcomes in those with positive treatment biopsies. Multivariate analysis indicated that the strongest predictor of biochemical failure was posttreatment biopsy status (positive vs severe treatment effect or negative p <0.001), followed by pretreatment prostate specific antigen (p = 0.05) and clinical T stage (p = 0.09). Similarly multivariate analysis revealed that a positive posttreatment biopsy was one of the strongest predictors of distant metastasis and prostate cancer death in this cohort of patients.
  
  
  CONCLUSIONS
  As assessed by posttreatment prostate biopsies, local control is improved with higher radiation doses. Long-term biochemical outcomes in patients with posttreatment biopsies demonstrating severe treatment effect changes were not different than those in patients with negative biopsies. We also noted that local tumor control was associated with a decrease in distant metastases and prostate cancer mortality, further highlighting the importance of achieving optimal tumor control in patients with clinically localized disease.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. zelefskm@mskcc.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Zvi
authors.initials: Z
authors.lastname: Fuks
authors.forename: Peter
authors.initials: P
authors.lastname: Scardino
authors.forename: Alison
authors.initials: A
authors.lastname: Shippy
mesh_terms: D000368:Aged; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D016019:Survival Analysis