contxhormbolla

"Focused on the Prostate since 1996"

Improved Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and Goserelin

TI - Prostate cancer patient subsets showing improved bNED control with
adjuvant androgen deprivation.

Improved Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and Goserelin

Michel Bolla, Dionisio Gonzalez, Padraig Warde, Jean Bernard Dubois, Rene-Olivier Mirimanoff, Guy Storme, Jacques Bernier, Abraham Kuten, Cora Sternberg, Thierry Gil, Laurence Collette, Marianne Pierart
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Abstract

Background. We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer.

Methods. From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin.

Results. Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P = 0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001).

Conclusions. Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer. (N Engl J Med 1997;337:295-300.)

Source Information

From University Hospital, Grenoble, France (M.B.); Akademisch Medisch Centrum, Amsterdam, the Netherlands (D.G.); Princess Margaret Hospital, Toronto (P.W.); Centre Regional de Lutte contre le Cancer Val d'Aurelle, Montpellier, France (J.B.D.); Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (R.-O.M.); Oncologisch Centrum, Brussels (G.S.); Ospedale San Giovanni, Bellinzona, Switzerland (J.B.); Rambam Medical Center, Haifa, Israel (A.K.); Ufficio Sternberg & Pansadoro, Rome (C.S.); and the European Organization for Research and Treatment of Cancer Data Center, Brussels (T.G., L.C., M.P.). Address reprint requests to Dr. Bolla at the Radiotherapy Department, University Hospital, B.P. 217 38043 Grenoble CEDEX 9, France.

Appendix

The following EORTC Radiotherapy Cooperative Group institutions participated in this study: Grenoble, Hopital Albert Michallon; Montpellier, Centre Val d'Aurelle; Dijon, Centre Georges-Francois Leclerc; Besancon, Hopital Jean Minjoz; Amsterdam, Akademisch Medisch Centrum; Heerlen, Radiotherapeutisch Instituut Limburg; Tilburg, B. Verbeeten Instituut; Lausanne, Centre Hospitalier Universitaire Vaudois; Bellinzona, Ospedale San Giovanni; Toronto, Princess Margaret Hospital; Haifa, Rambam Medical Hospital; Jerusalem, Hadassah University Hospital; Tel Aviv, Tel Aviv Medical Center-Ichilov Hospital; Valencia, Instituto Valenciano de Oncologia; and Portsmouth, St. Mary's Hospital.

The following EORTC Genitourinary Group institutions participated in this study: Maastricht, Akademisch Ziekenhuis; Rotterdam, Zuiderziekenhuis; Brussels, Akademisch Ziekenhuis; Kortrijk, St. Maarten Hospital; Leuven, Universitair Ziekenhuis Sint Rafael; Antwerp, Universitair Ziekenhuis; Rome, Ufficio Sternberg & Pansadoro; Malta, St. Luke's Hospital; Newcastle-upon-Tyne, Freeman Hospital; Obninsk, Medical Radiological Research Center; and Oslo, Norwegian Radium Hospital.

AU - Anderson PR; Hanlon AL; Movsas B; Hanks GE

TI - Prostate cancer patient subsets showing improved bNED control with
adjuvant androgen deprivation.

SO - Int J Radiat Oncol Biol Phys 1997;39(5):1025-30
AD - Department of Radiation Oncology Fox Chase Cancer Center, Philadelphia,
PA 19111, USA.
AB - PURPOSE: Cooperative groups have investigated the outcome of androgen
deprivation therapy combined with radiation therapy in prostate
cancer patients with variable pretreatment prognostic indicators.
This report describes an objective means of selecting patients for
adjuvant hormonal therapy by a retrospective matched case/control
comparison of outcome between patients with specific pretreatment
characteristics who receive adjuvant hormones (RT+H) vs. patients
with identical pretreatment characteristics treated with radiation
therapy alone (RT). In addition, this report shows the 5-year bNED
control for patients selected by this method for RT+H vs. RT alone.
METHODS AND MATERIALS: From 10/88 to 12/93, 517 T1-T3 NXM0 patients
with known pretreatment PSA level were treated at Fox Chase Cancer
Center. Four hundred fifty-nine of those patients were treated with
RT alone while 58 were treated with RT+H. The patients were
categorized according to putative prognostic factors indicative of
bNED control, which include the palpation stage, Gleason score, and
pretreatment PSA. We compared actuarial bNED control rates according
to treatment group within each of the prognostic groups. In addition,
we devised a retrospective matched case/control selection of RT
patients for comparison with the RT+H group. Five-year bNED control
was compared for the two treatment groups, excluding the best
prognosis group, using 56 RT+H patients and 56 matched (by stage,
grade, and pretreatment PSA level) controls randomly selected from
the RT alone group. bNED control for the entire group of 517 patients
was then analyzed multivariately using step-wise Cox regression to
determine independent predictors of outcome. Covariates considered
for entry into the model included stage (T1/T2AB vs. T2C/T3), grade
(2-6 vs. 7-10), pretreatment PSA (0-15 vs. > 15), treatment (RT vs.
RT+H), and center of prostate dose. bNED failure is defined as PSA >
or = 1.5 ngm/ml and rising on two consecutive determinations. The
median follow-up for the 112 matched case/control patients was 41
months. The median follow-up was 46 months for the RT (range 11-102
months) and 37 months for the RT+H group (range 6-82 months).
RESULTS: Univariate analysis according to treatment for the
prognostic factors of palpation stage, Gleason score, and pretreatme-
nt PSA demonstrates a significant improvement in 3-year bNED control
with the addition of hormones for patients with T2C/T3, Gleason score
7-10, or pretreatment PSA > 15 ngm/ml. A comparison of bNED control
according to treatment demonstrates improvement in 5-year bNED
control of 55% for patients treated with RT+H vs. 31% for those
patients treated with RT alone (p = 0.0088), although there is not a
survival advantage. Multivariate analysis demonstrates that hormonal
treatment is a highly significant independent predictor of bNED
control (p = 0.0006) along with pretreatment PSA (p = 0.0001),
palpation stage (p = 0.0001), grade (p = 0.0030), and dose (p =
0.0001). CONCLUSIONS: (1) Patients with specific adverse pretreatment
prognostic factors (i.e., T2C/T3, Gleason score 7-10, pretreatment
PSA > 15) benefit from adjuvant hormonal therapy. (2) Upon multivari-
ate analysis, hormonal therapy is determined to be a highly
significant predictor of bNED control, after adjusting for all other
covariates. (3) The 5-year bNED control rates of 55% for RT+H vs. 31%
for RT alone represents the magnitude of benefit from adjuvant
hormone therapy. (4) The bNED control curves are separated by about
20 months, representing a delay in disease progression with adjuvant
hormonal therapy, as there is no overall survival difference.