title: Anatomical Patterns of Recurrence Following Biochemical Relapse in the Dose Escalation Era of External Beam Radiotherapy for Prostate Cancer.
abstract: OBJECTIVE
  We provide a comprehensive analysis of anatomical patterns of recurrence following external beam radiotherapy in patients with localized prostate cancer.
  
  
  METHODS
  This retrospective analysis included 2,694 patients with localized prostate cancer who received definitive, dose escalated external beam radiotherapy from 1991 to 2008. First recurrence sites were defined as initial sites of clinically detected recurrence and any subsequent clinically detected recurrence within 3 months. Anatomical recurrence patterns were classified as local (prostate/seminal vesicles only), lymphotropic (lymph nodes only) and osteotropic (bones only) in patients with disease confined only to these respective sites for at least 2 years from the initial clinically detected recurrence.
  
  
  RESULTS
  Prostate was the most common first recurrence site in the low, intermediate and high risk groups with an 8-year cumulative incidence of 3.5%, 9.8% and 14.6%, respectively. The 8-year risk of isolated pelvic lymph node relapse as the first recurrence site was 0%, 1.0% and 3.3%, respectively. In the 474 patients with clinically detected recurrence the most common first recurrence site was local in 55.3%, bone in 33.5%, pelvic lymph nodes in 21.3% and abdominal lymph nodes in 9.1%. Patients showed unique relapse distributions, including a pattern that was local in 41.6%, lymphotropic in 9.7%, osteotropic in 20.3% and multiorgan/visceral in 28.5%. Anatomical recurrence pattern was the strongest predictor of prostate cancer specific mortality on multivariate analysis of patients with clinically detected recurrence.
  
  
  CONCLUSIONS
  The most common first recurrence site after dose escalated external beam radiotherapy for prostate cancer is in the prostate and seminal vesicles in all risk groups. In contrast, patients treated without elective pelvic lymph node irradiation are at relatively low risk for isolated pelvic lymph node relapse. Recurrence patterns revealed a tropism for specific anatomical distributions with divergent prognoses, suggesting underlying biological differences among tumors.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Zumsteg
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Spratt
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Paul B
authors.initials: PB
authors.lastname: Romesser
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Xin
authors.initials: X
authors.lastname: Pei
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Marisa
authors.initials: M
authors.lastname: Kollmeier
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Sean
authors.initials: S
authors.lastname: McBride
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ).
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ). Electronic address: zelefskm@mskcc.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D012669:Seminal Vesicles / Q000473:pathology; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: lymph nodes; prostatic neoplasms; radiotherapy; recurrence; treatment failure