The importance of prognostic factors in the interpretation of two EORTC metastatic prostate cancer trials. European Organization for Research and Treatment of Cancer (EORTC) Genito-Urinary Tract Cancer Cooperative Group.
OBJECTIVE
The EORTC conducted two randomized phase III trials of maximal androgen blockade (MAB) in 695 patients with metastatic prostate cancer. Trial 30,843 compared orchidectomy or buserelin to buserelin plus cyproterone acetate and showed no significant difference in survival while trial 30,853 showed that Zoladex plus flutamide had a significantly longer survival than orchidectomy. Reasons for this discrepancy were sought.


METHODS
In order to determine whether differences in patient characteristics could explain these possibly contradictory results, a Cox proportional hazards regression model was used to identify prognostic factors for survival in each study. Patients were divided into risk groups (good or poor prognosis with 3.5 and 1.75 years' median survival, respectively) based on their alkaline phosphatase, hemoglobin, performance status, pain score, T category and G grade at entry on study.


RESULTS
The survival advantage of MAB in 30,853 was limited to patients with a good prognosis (164/302 (54%) of the patients). In 30,843, only 93/337 patients (28%) had a good prognosis so there were insufficient data to draw separate conclusions in these patients. Despite the limitations of subgroup analyses, these results show that patients in 30,843 had on the average a worse prognosis than patients in 30,853. Hence there were fewer good prognosis patients who could potentially benefit from MAB, thus providing one possible explanation for the overall negative conclusion.


CONCLUSIONS
These studies once again underline the importance of taking into account patient characteristics when designing and interpreting metastatic prostate cancer trials. They also provide criteria which may be used to define risk groups as part of a protocol's patient eligibility criteria. In the design of future trials assessing MAB, a sufficient number of good prognosis patients should be entered to reliably assess treatment efficacy in this subgroup.
Sylvester
R J
RJ
EORTC Data Center, Brussels.
Denis
L
L
de Voogt
H
H
D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D002064:Buserelin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D017373:Cyproterone Acetate / Q000008:administration & dosage; D018572:Disease-Free Survival; D005485:Flutamide / Q000008:administration & dosage; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009919:Orchiectomy; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018570:Risk Assessment; D015996:Survival Rate
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D017373:Cyproterone Acetate; D005485:Flutamide; D002064:Buserelin