Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study.
OBJECTIVE
The development of conformal radiation technique including improved patient immobilization has allowed us to test the value of dose escalation in optimizing the radiation treatment of prostate cancer.


METHODS
Outcome is reported for 233 consecutive patients treated with conformal technique between March 1989 and October 1992. Dose was escalated from 68 Gy to 79 Gy. Patient status is reported at 3 years follow-up, which is available in all alive patients. Pretreatment and serial posttreatment prostate specific antigen (PSA) values are available for all patients. Biochemical freedom of disease (bNED) defines failure as PSA > 1.5 ngm/ml and rising on two consecutive measures. Dose response for bNED control of cancer and late morbidity are represented by logit response models fitted to the data. Kaplan-Meier methods, the log rank test, and Cox Regression models are also used.


RESULTS
No dose response is observed for bNED survival for patients with pretreatment PSA <10 ngm/ml comparing patients treated above or below 71.5 Gy or on multivariate analysis. Dose response is observed for bNED survival for pretreatment PSA groups of 10-19.9 ngm/ml and 20+ ngm/ml. The dose associated with 50% bNED survival at 3 years is 64 Gy and 76 Gy, respectively. The slope of the dose responses are 13 and 9%, respectively. Dose response is demonstrated for Grade 2 gastrointestinal (GI), Grade 2 genitourinary (GU), and Grade 3,4 combined GI and GU late morbidity. The slopes of the morbidity responses are steeper than for cancer control (19 to 21%).


CONCLUSIONS
Patients with pretreatment PSA < 10 ngm/ml do not benefit from dose escalation, and the serious late morbidity of conformal radiation at 70 Gy is < 3%. Patients with PSA values 10-19.9 ngm/ml and 20+ ngm/ml benefit from dose escalation beyond 70 Gy. Treatment beyond 75 Gy results in > 10% serious morbidity unless special precautions are taken to protect the rectal mucosa. All levels of severity of radiation morbidity show a dose response and combined with the dose response for bNED survival these data allow the optimization of treatment.
Hanks
G E
GE
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Schultheiss
T E
TE
Hanlon
A L
AL
Hunt
M
M
Lee
W R
WR
Epstein
B E
BE
Coia
L R
LR
D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011247:Pregnancy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D011881:Radiotherapy, Computer-Assisted; D012044:Regression Analysis; D017211:Treatment Failure
D017430:Prostate-Specific Antigen