title: Long-term outcome after elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for locally advanced prostate cancer.
abstract: OBJECTIVE
  To report the 8-year outcome of local dose escalation using high-dose-rate conformal brachytherapy combined with elective irradiation of the pelvic lymphatics for localized prostate cancer.
  
  
  METHODS
  One hundred forty-four consecutively treated men (1986-1992) were recorded prospectively. Twenty-nine (20.14%) patients had T1b-2a tumors, and 115 (79.86%) patients had T2b-3 tumors according to, respectively, American Joint Committee on Cancer/Union Internationale Contre le Cancer 1992. All patients had a negative nodal status, proven by CT or MRI. The mean initial PSA value was 25.61 ng/mL (Initial value for 41.66% of patients was <10 ng/mL, for 21.52% was 10-20 ng/mL, and for 32.63% was >20 ng/mL). The total dose applied by external beam radiotherapy was 50 Gy in the pelvis and 40 Gy in the prostate. The high-dose-rate brachytherapy was delivered in two fractions, which were incorporated into the external beam treatment (after 20-Gy and 40-Gy external beam radiotherapy dose). The dose per fraction was 15 Gy for the PTV1 (peripheral prostate zone) and 9 Gy for the PTV2 (entire prostatic gland). Any patient free of clinical or biochemical evidence of disease was termed bNED. Actuarial rates of outcome were calculated by Kaplan-Meier and compared using the log-rank. Cox regression models were used to establish prognostic factors of the various measures of outcome.
  
  
  RESULTS
  The median follow-up was 8 years (range 60-171 months). The overall survival rate was 71.5%, and the disease-free survival rate was 82.6%. The bNED survival rate was 72.9%. Freedom from local recurrence for T3 stage was 91.3%, whereas for G3 lesions it was 88.23%. Freedom from distant recurrence for T3 stage was 82.6% and for G3 lesions 70.59%. Univariate survival analyses revealed that low stage (T1-2), low grade (G1-2), no hormonal therapy, initial PSA value less than 40 ng/mL, and PSA normalization <1.0 ng/mL after irradiation were associated with long survival. In multivariate analyses, initial PSA value, PSA kinetics after radiation therapy, and no adjuvant hormonal treatment were independent prognostic factors. Grade 3 late radiation toxicity (according to RTOG/EORTC scoring scheme) was 2.3% for the genitourinary system in terms of cystitis and 4.10% for the gastrointestinal system in terms of proctitis. Grades 4 and 5 genitourinary/gastrointestinal morbidity was not observed. A history of transurethral resection of the prostate with a median interval of less than 6 months from radiotherapy was associated with a high risk of genitourinary toxicity.
  
  
  CONCLUSIONS
  The 8-year results confirm the feasibility and effectiveness of combined elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for cure of localized and especially high-risk prostate cancer.
authors.affiliation: Interdisciplinary Brachytherapy Center, Clinic for Radiation Therapy (Radio-oncology), University Hospital, Christian-Albrechts-University, Kiel, Germany. galalae@onco.uni-kiel.de
authors.forename: Razvan M
authors.initials: RM
authors.lastname: Galalae
authors.forename: Gyoergy
authors.initials: G
authors.lastname: Kovács
authors.forename: Juergen
authors.initials: J
authors.lastname: Schultze
authors.forename: Tillmann
authors.initials: T
authors.lastname: Loch
authors.forename: Peter
authors.initials: P
authors.lastname: Rzehak
authors.forename: Roland
authors.initials: R
authors.lastname: Wilhelm
authors.forename: Hagen
authors.initials: H
authors.lastname: Bertermann
authors.forename: Britta
authors.initials: B
authors.lastname: Buschbeck
authors.forename: Peter
authors.initials: P
authors.lastname: Kohr
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kimmig
mesh_terms: D000704:Analysis of Variance; D005500:Follow-Up Studies; D006801:Humans; D015182:Lymphatic Irradiation / Q000379:methods*; D008297:Male; D009367:Neoplasm Staging; D010388:Pelvis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000379:methods*; D015996:Survival Rate; D020728:Transurethral Resection of Prostate; D016896:Treatment Outcome; D014549:Urinary Incontinence / Q000209:etiology
chemical_list: D017430:Prostate-Specific Antigen