Further Research Needed to Inform the Management of Post-Chemo Residual Nonretroperitoneal Disease in Testicular Cancer

Jennifer M. King, MD

Teratoma in the primary tumor site was associated with a higher incidence of teratoma in residual nonretroperitoneal (non–RP) disease post-chemotherapy, according to findings from a retrospective study. However, this feature could not be used to conclusively identify patients with nonseminomatous germ cell tumors who could forgo surgical resection. Accordingly, more research is needed to inform recommendations for surveillance and resection in this patient subset,according to Jennifer M. King, MD.

A retrospective review of 129 patients with non–RP residual disease post-chemotherapy identified 75 patients who had teratoma in the primary tumor site. Of these patients, 41 (55%) had teratoma, 23 (31%) had non-teratoma active germ cell tumor, and 21 (28%) had necrosis in the resected tumor. Regarding patients without teratoma in the primary tumor, 9 (17%) had at least one non-teratomatous element, 30 (56%) had non-teratoma active germ cell tumor, and 20 (37%) had necrosis in the resected non–RP specimens.

Investigators found that the presence of teratoma in the primary tumor may be predictive of teratomatous elements in postchemotherapy residual non–RP disease for patients who do not undergo retroperitoneal lymph node dissection. However, both groups of patients had comparable rates of teratoma or active germ cell tumor in residual non–RP disease.

“The most important thing is that we didn’t find any clear criteria to recommend surveillance or observation of residual non–RP disease,” said King, who is an assistant professor of clinical medicine in the Department of Medicine, Division of Hematology/Oncology, at Indiana University (IU) School of Medicine in Indianapolis and a physician-scientist at the IU Melvin and Bren Simon Comprehensive Cancer Center. “... [Therefore,] the absence of teratoma in the primary should not preclude surgical resection of this disease.”

In an interview with OncLive^®, King expanded on the design and methodology of this retrospective review, shared key findings regarding the correlation between teratoma in the primary tumor and rates of post-chemotherapy teratoma in residual non–RP disease, and emphasized the need for more data to inform management decisions in residual non–RP testicular cancer.

OncLive: What was the rationale for investigating factors that may guide the management of residual non–RP disease in post-chemotherapy nonseminomatous germ-cell tumors?

King: Testicular cancer is a great success story. Most patients are cured with first-line chemotherapy, but there [are some] patients who have residual disease after chemotherapy. Most of the time those patients have RP residual disease in addition to non-RP disease, but there is a subset of patients who have only residual non––RP disease without any residual RP disease. There’s limited data on how to guide the management of those patients and identify who truly needs resection so that we can try to minimize the treatment burden for these patients as much as possible.

Please describe the design and key objectives of this study.

This was a retrospective review using our Indiana University testicular cancer database. Previous work has demonstrated an association between having teratoma in the primary [tumor site] and having teratoma in the residual RP disease. Our main objective with this study was to determine if the presence of teratoma in the primary orchiectomy was associated with a higher rate of teratoma in post-chemotherapy residual non–RP disease.

Could you expand on the patient population that was included in the study? Were there any notable baseline characteristics?

Patients with metastatic non-seminoma, who had residual non–RP disease in the absence of any residual RP disease were included. [These patients had residual non–RP disease] either post first-line chemotherapy or post salvage chemotherapy. Some patients were included who did have RP metastasis at the time of diagnosis, but their RP disease normalized after chemotherapy. Over half of patients who were included were International Germ Cell Cancer Collaborative Group [IGCCCG] intermediate or high risk, and the majority of the non–RP resection sites were lung resections. About 65% of patients had a lung resection. Other [resection sites] included [the] liver and bone, as well as cervical and mediastinal lymph nodes.

What did this study reveal about the prevalence of teratoma and active germ cell tumor in patients with residual non–RP disease alone following chemotherapy?

Of the patients who had teratoma in their primary orchiectomy site, 55% had at least 1 post-chemotherapy non–RP resection with teratoma. In those who did not have teratoma in the primary, that percentage was only 17%. That was statistically significant. In those who did not have teratoma in the primary [tumor site], 56% had active germ cell tumor in the residual non–RP disease. That was compared [with] 31% of patients who had teratoma in the primary [orchiectomy site] and was also statistically significant.

We [also] found that teratoma in the primary site was associated with a higher rate of teratoma in non–RP residual disease.

What did findings indicate about the need for surgical resection in patients without teratoma in the primary tumor?

What’s important [to note] with these data is [that] we couldn’t find clear criteria to recommend observation for these patients [over resection]. Patients who had teratoma in the primary [did] have a higher rate of teratoma in the residual non–RP disease. [However], there were pretty high rates of active germ cell tumor in patients who did not have teratoma in the primary.

We tried to identify other factors like tumor markers or either first-line chemotherapy vs salvage chemotherapy, [but] we still could not find a correlation between these other factors and the presence of either active germ cell tumor or teratoma.

Were any results from this study particularly surprising?

Interestingly, we found higher rates of active germ cell tumor in the residual non–RP disease for all sites when we compare that to the 10% to 15% chance of having active germ cell tumor in RP residual disease. We’re not entirely clear why that is, but we postulate that it has something to do with differences in the biology for hematogenous metastasis compared with lymphatic metastasis, like you would see with RP disease.

What limitations from this study are important to note?

This was a retrospective study, so selection bias was a limitation. [However,] one benefit of our testicular cancer database is that it is prospectively maintained, so we included consecutive patients who are seen at our institution.

What next steps are planned for this research?

Our next step would be looking at outcomes for this patient population. Previous work has found no impact on survival for patients who have teratoma either in the primary site or in residual RP disease. We are looking to evaluate [this impact on] outcomes for this subset of patients who have residual non–RP disease.

What ongoing or future research in the field of genitourinary cancer are you most excited about?

Moving forward, there’s a lot of exciting research into microRNA and circulating tumor DNA. This is an area that may help to further delineate patients who truly need to undergo surgical resection vs those who could be safely followed with surveillance.

Reference

King JM, Cheng M, Kesler K, et al. Management of residual nonretroperitoneal disease in postchemotherapy nonseminomatous germ-cell tumors. J Clin Oncol. Published online February 9, 2023. doi:10.1200/JCO.22.02205