Dr. Einhorn then segued into differences in risk stratification as defined by the International Germ Cell Cancer Collaborative Group. Approximately one-quarter of all cases present as poor-risk disease, 15% as intermediate-risk, and 60% as good-risk. He stressed that the proper serum marker levels used to determine risk status are at the time of chemotherapy commencement.
In the poor-risk population, Dr. Einhorn emphasized the standard of care as BEP x 4 or vinblastine, ifosfamide, and cisplatin (VIP) x 4. Moreover, he noted that when studies from the 1970s are used to compare outcomes, the newer studies will always appear better because inferior regimens were included in the 1970s. In the intermediate-risk group, Dr. Einhorn noted that most guidelines recommend BEP x 4. However, he believes that BEP x 4 represents overtreatment for most patients, but he prefers selecting patients from the intermediate-risk group for options with less toxicity. Patients with good-risk disease are either slotted for BEP x 3 or BEP x 4. He observed that virtually all phase-III studies have shown either numerical or statistically improved outcomes when bleomycin is included. Thus, he only chooses BEP x 4 for patients older than 50 years of age, those with inherent significant lung disease, and patients with impaired renal function (creatinine > 5 mg/dL).
Individuals with primary mediastinal nonseminomatous germ-cell tumors (NSGCTs)are difficult to treat. At Indiana, a change was made from BEP x 4 to VIP x 4 due to fewer pulmonary complications using the latter regimen. Of 221 patients undergoing postchemotherapy surgical resection, 13% of the BEP group (n = 166) vs. 0% of the VIP group (n = 55) had grade 4-5 toxicities. Furthermore, there were 11 postoperative mortalities in the BEP group compared with none in the VIP group. Thus, Dr. Einhorn believes that BEP should not be given in primary mediastinal NSGCTs.
For those with clinical-stage-1 NSGCTs, four options for treatment exist: nerve-sparing retroperitoneal lymph-node dissection, BEP x 1, BEP x 2, and surveillance. Dr. Einhorn advocated against BEP x 2, explaining that if there was a certainty that only one cancer cell remained in the retroperitoneum, the patient should receive retroperitoneal lymph-node dissection. If Dr. Einhorn was sure that there was only one cancer cell in the person’s lung, he would use BEP x 1. And if the patient had no other cancer, he or she should go on active surveillance. Of course, we are not currently able to obtain this level of sophistication, he reported.
Lastly, Dr. Einhorn considered salvage therapy, in which the options in this setting are high-dose chemotherapy with peripheral stem-cell transplant; vinblastine, ifosfamide, cisplatin (also called VeIP); or paclitaxel, ifosfamide, cisplatin (also called TIP) x 4; and salvage surgery. In patients with a relapse within 4 weeks of standard-dose cisplatin combination chemotherapy, he believes that immediate high-dose chemotherapy is the best option.Of 304 patients at Indiana, 230 (63%) achieved continuous NEDstatus, which was most pronounced among patients with seminoma where 67/79 (85%) showed NED.
Dr. Einhorn concluded with a discussion of testicular cancer’s role in the remarkable success story of platinum-based chemotherapy. Early on, toxicity profiles outweighed any therapeutic advantage. However, testis cancer was the first malignancy to show a benefit. Now, platinum has demonstrated clinical utility in 11 solid tumors.
Presenter: Lawrence H. Einhorn, MD, Indiana University Melvin and Bren Simon Cancer Center
Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA