Early trials of adjuvant chemotherapy

Before the advent of cisplatin-based chemotherapy, patients who had completely resected node-positive disease (pN1 and pN2) were offered either no adjuvant chemotherapy, minimally effective chemotherapy, or postoperative radiotherapy [15,16]. The relapse rate in this patient population was 20% to 70%, with most studies showing a relapse rate of 50% to 60% [17]. As cisplatin-based chemotherapeutic regimens were found to be effective in stage III GCT, these regimens were studied in the adjuvant setting. The hope was to decrease the proportion of patients who relapsed after RPLND and to increase the proportion of patients who were cured. These early trials of adjuvant chemotherapy are summarized in Table 2. The regimens, which

Table 1

Pathologic staging of regional lymph nodes after retroperitoneal lymph node dissection

Stage Lymph node status pN0 No regional lymph node metastases pN1 Lymph node mass <2 cm at greatest dimension; or multiple lymph nodes, none >2 cm in greatest dimension pN2 Lymph node mass > 2 cm but not >5 cm in greatest dimension; or multiple lymph nodes, any one mass > 2 cm but not > 5 cm in greatest dimension; or any evidence of extranodal extension pN3 Lymph node mass > 5 cm in greatest dimension included cisplatin, vinblastine, and bleomycin, were superior to prior trials of non-platinum-based chemotherapy.

One non-platinum-containing regimen studied at Memorial Sloan-Kettering Cancer Center (MSKCC) was "mini-VAB," which consisted of vinblastine, dactinomycin, bleomycin, and chlor-ambucil. This regimen proved ineffective because of the lack of cisplatin, but the experience with mini-VAB was useful in defining the relapse pattern for patients who had completely resected stage II disease. The patients were retrospectively grouped, using the older classification system, into stage IIA (microscopically positive or grossly positive with <6 nodes, all nodes <2 cm in diameter) and stage IIB disease (R6 nodes involved, and/or any node >2 cm, or extranodal extension) [18]. No patient who had stage IIA disease relapsed, whereas a relapse proportion of 34% was seen in patients who had stage IIB disease [18]. Since this trial, therefore, adjuvant therapy has not been routinely offered to compliant patients who have low-volume nodal involvement (pN1), and cisplatin-based chemotherapy has been administered to patients who have highvolume disease (pN2).

Cisplatin-, bleomycin-, and vinblastine-con-taining regimens (PVB) have resulted in a disease-free survival of greater than 90% in patients who have advanced-stage disease [18-20]. Consistent with the treatment of patients who have advanced GCT, efforts in the management of completely resected stage II nonseminoma focused on maintaining efficacy while decreasing treatment-related morbidity.

One randomized study involving 225 patients compared two versus four cycles of adjuvant PVB. This trial showed that both groups had an equally high survival rate after a median follow-up of 43 months [21]. Patients treated with four cycles of therapy had more toxicity, but no appreciable improvement in survival. The trial established two cycles of therapy as standard in patients who had completely resected stage II nonseminomatous germ cell tumor after RPLND. This study also focused on the use of surveillance, with chemotherapy withheld until relapse, and better-tolerated cisplatin-based adjuvant regimens, in an effort to decrease toxicity and maintain a high cure rate.

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