Assessing prognosis and optimizing treatment in patients with postchemotherapy viable NSGCT (2/28/2008)

In nonseminomatous germ-celltumors (NSGCT), surgical resection of postchemotherapy residualmasses is universally recommended. These masses may harbor completenecrosis, teratoma, or viable malignant germ-cell tumors (GCT). Besides viable GCT, postchemotherapy residual masses can also harbor non-GCT cancer, especially in primary mediastinal NSGCT, and this so-called 'teratoma with malignant transformation' is associated with a dismal prognosis. In patients with postchemotherapy retroperitoneal and pulmonary lesions, discordant histologies between the two sites have been reported in approximately 30% of cases, thus justifying the removal of lesions from both sides of the diaphragm. However, the high pathological concordance rate (95%) between residual lesions from both lungs argues in favor of avoiding a contralateral thoracotomy when complete necrosis is identified in operative specimens from the one lung.

The presence of viable cells in completely resected residual masses has been designated a 'surgical complete response' (sCR). In some cases, this may indicate resistance to cisplatin and a worse prognosis compared with specimens with residual teratoma or necrosis/fibrosis alone. Until recently, the rarity of this situation has made it difficult to power studies with sufficient number of patients to reliably identify relevant risk factors. In 2001, a multi-institutional study group from France, Norway, USA, Italy, Germany, Austria, Denmark and Russia reported in Annals of Oncology on 238 patients with postchemotherapy viable NSGCT. Since the sCR1 study was based on a single series of patients without a validation set and the assessment of viable NSGCT was carried out locally at the individual sites, the group validated these prognostic factors using a separate set of patients with a central review of pathological tumor specimens.

Data and specimens from 61 patients with normalized tumor markers and who were postchemotherapy viable nonteratomatous NSGCT treated were collected. With a median follow-up of 5.4 years, the 5-year progression-free survival (PFS) rate was 65%; the 5-year overall survival (OS) rate was 72%. Favorable PFS was predicted by a complete resection, less than 10% of viable malignant cells, and a good International Germ Cell Consensus Classification group at presentation. Patients were assigned to one of three risk groups defined in sCR1: no risk factor (good risk), one risk factor (intermediate risk) and two to three risk factors (poor risk group). The 5-year PFS rate was 92%, 78%, and 42%, respectively (P = 0.002) as compared with 90%, 76%, and 41% in the original sCR1 study. The 5-year OS rate was 90%, 86%, and 52%, respectively (P =0.009), as compared with 100%, 83%, and 51% in the originals CR1 study.

In patients with postchemotherapy viable NSGCT, a complete resection of residual masses should be rigorously pursued. These data validate the sCR1 prognostic index. Given their excellent outcome, patients in the favorable group may not require postoperative chemotherapy. Consequently, in the absence of strong evidence-based data, oncologists may consider either immediate postoperative chemotherapy or surveillance with treatment in case of a relapse in patients with postchemotherapy viable malignant cells allocated to the intermediate or poor risk groups. The concept of using postoperative chemotherapy in this setting should be revisited in the future when more active agents/regimens are hopefully identified in cisplatin-resistant NSGCT.

Note: This story has been adapted from a news release issued by the European Society for Medical Oncology

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