Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma.
BACKGROUND
The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT).


METHODS
A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale.


RESULTS
Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction.


CONCLUSIONS
The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.
Zelefsky
M J
MJ
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cowen
D
D
Fuks
Z
Z
Shike
M
M
Burman
C
C
Jackson
A
A
Venkatramen
E S
ES
Leibel
S A
SA
D000230:Adenocarcinoma / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D007172:Erectile Dysfunction / Q000209:etiology; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D016896:Treatment Outcome; D014570:Urologic Diseases / Q000209:etiology