Long-Term Outcome of High Dose
Intensity Modulated Radiation Therapy
for Patients With Clinically Localized Prostate Cancer
Michael J. Zelefsky,*,† Heather Chan,† Margie Hunt,† Yoshiya Yamada,‡ Alison M. Shippy† and
From the Departments of Radiation Oncology (MJZ, HC, YY) and Medical Physics (MH, HA), Memorial Sloan-Kettering Cancer Center,
New York, New York
Purpose: We report on the long-term results and late toxicity outcomes of high dose intensity modulated radiation therapy
for patients with clinically localized prostate cancer.
Materials and Methods: Between 1996 and 2000 a total of 561 patients with clinically localized prostate cancer were
treated with intensity modulated radiation therapy. All patients were treated to a dose of 81 Gy prescribed to the planning
target volume. Prostate specific antigen relapse was defined according to the American Society for Therapeutic Radiology and
Oncology consensus and Houston definitions (absolute nadir plus 2 ng/ml dated at the call). Median followup was 7 years
(range 5 to 9).
Results: The 8-year actuarial PSA relapse-free survival rates for patients in favorable, intermediate and unfavorable risk
groups according to the American Society for Therapeutic Radiology and Oncology definition were 85%, 76% and 72%,
respectively (p ?0.025). The 8-year actuarial prostate specific antigen relapse-free survival rates for patients in favorable,
intermediate and unfavorable risk groups according to the Houston definition were 89%, 78% and 67%, respectively
(p ? 0.0004). The 8-year actuarial likelihood of grade 2 rectal bleeding was 1.6%. Three patients (0.1%) experienced grade 3
rectal toxicity requiring either 1 or more transfusions or a laser cauterization procedure. No grade 4 rectal complications have
been observed. The 8-year likelihood of late grade 2 and 3 (urethral strictures) urinary toxicities were 9% and 3%,
respectively. Among patients who were potent before intensity modulated radiation therapy, erectile dysfunction developed
in 49%. The cause specific survival outcomes for favorable, intermediate and unfavorable risk cases were 100%, 96% and 84%,
Conclusions: These long-term results confirm our previous observations regarding the safety of high dose intensity
modulated radiation therapy for clinically localized prostate cancer. Despite the application of high radiation doses, the
incidence of rectal bleeding at 8 years was less than 2%. Despite the increased conformality of the dose distribution associated
with intensity modulated radiation therapy, excellent long-term tumor control outcomes were achieved.
Key Words: radiotherapy, intensity-modulated; prostatic neoplasms; toxicity
clinically localized prostate cancer. These studies have pro-
vided convincing evidence for improved tumor control out-
comes with the application of higher radiation dose levels.1–9
Based on published reports it appears that dose levels of at
least 78 Gy, and likely even higher, are necessary to achieve
optimal tumor control outcomes. One of the significant lim-
itations of high dose radiotherapy delivery has been the
potential for an increased risk of long-term morbidity. Sev-
eral studies have confirmed increased risks of urinary and
rectal toxicities with the use of higher radiation doses.10–12
nhanced methods of delivering external beam radia-
tion doses in a highly precise fashion have paved the
way for dose escalation trials in the treatment of
In a report of the outcomes of the phase III randomized trial
from MD Anderson Hospital, among those patients who
received the 78 Gy dose, the 5-year incidence of grade 2 to 3
rectal toxicity was 25%. In addition, chronic proctitis was
more likely when an increased volume of the rectum was
exposed to these higher dose levels.11
We introduced intensity modulated radiation therapy in
1996 at our institution to facilitate dose escalation therapy
by further enhancing the conformality of the dose distribu-
tion around the tumor target, and reducing the volume of
rectum and bladder exposed to high doses of radiotherapy.
In our initial experience we observed substantially lower
rectal dose levels when IMRT treatment planning was used
compared to 3D-conformal treatment planning. With 2-year
followup observations we noted a significant reduction in the
Submitted for publication November 10, 2005.
* Correspondence and requests for reprints: Department of Radi-
ation Oncology, Memorial Sloan-Kettering Cancer Center, 1275
York Ave., New York, New York 10021 (telephone: 212-639-6802;
FAX: 212-639-8876; e-mail: firstname.lastname@example.org).
† Nothing to disclose.
‡ Financial interest and/or other relationship with Varian Medi-
Editor’s Note: This article is the third of 5 published in
this issue for which category 1 CME credits can be
earned. Instructions for obtaining credits are given
with the questions on pages 1690 and 1691.
THE JOURNAL OF UROLOGY®
Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 176, 1415-1419, October 2006
Printed in U.S.A.