Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review.
OBJECTIVE
Patients with clinical stage I nonseminomatous testicular germ cell tumor should ideally receive adjuvant therapy only when they are at high risk for occult metastasis. We aimed to quantify the importance of predictors for occult metastasis by performing a systematic review of the relevant literature. In addition, we reviewed published multivariable models and risk-adapted treatment policies.


METHODS
We identified 23 publications between 1979 and 2001, reporting a total of 2,587 patients. Twenty-nine percent of the patients (759 of 2,587 patients) had occult metastases, which was diagnosed either at retroperitoneal lymph node dissection (n = 193) or during follow-up (n = 566). Odds ratios (OR) were pooled using meta-analysis techniques.


RESULTS
The presence of vascular invasion of the primary tumor cells had the strongest effect (OR, 5.2; 95% CI, 4.0 to 6.8). Immunohistochemical staining of the primary tumor cells with the MIB-1 monoclonal antibody showing proliferative activity was a promising predictor (OR, 4.7; 95% CI, 2.0 to 11). Intermediate effects were found for embryonal carcinoma in the primary tumor (OR, 2.9; 95% CI, 2.0 to 4.4) and a high pathologic stage of the tumor (OR, 2.6; 95% CI, 1.8 to 3.8). Size of the primary tumor and age of the patient had weaker though also statistically significant associations with occult metastasis. Until now, multivariable models often included vascular invasion and embryonal carcinoma with one or two weaker predictors. None of the published risk-adapted treatment policies included MIB-1 staining.


CONCLUSIONS
Several strong predictors for occult metastasis were identified. A risk-adapted treatment policy should be developed that incorporates all relevant predictors so that adjuvant therapy is targeted better to those with occult metastases.
Vergouwe
Yvonne
Y
Center for Clinical Decision Sciences, Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. y.vergouwe@erasmusmc.nl
Steyerberg
Ewout W
EW
Eijkemans
Marinus J C
MJ
Albers
Peter
P
Habbema
J Dik F
JD
D000328:Adult; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis; D018237:Germinoma / Q000737:chemistry / Q000556:secondary* / Q000601:surgery; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000737:chemistry / Q000556:secondary* / Q000601:surgery
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C440408:MIB-1 antibody