Although patients with poor-risk metastatic testicular germ cell tumors continue to have less favorable outcomes, the bar has been raised by contemporary treatment. There is still room for improvement in managing metastatic testicular germ cell tumors, especially in poor-risk patients, but if poor-risk patients treated with modern curative therapy survive for more than 2 years, their risk of relapse and survival are similar to those of favorable/intermediate-risk patients.

These were the findings of two studies presented at the 2016 Genitourinary Cancers Symposium: a multi-institutional study of patients with metastatic testicular germ cell tumors treated with first-line curative therapy from 1990 to 2012¹ and a single-institution study of patients treated from 1998 to 2012.²

Conditional Survival

The first study evaluated conditional survival in patients with metastatic testicular germ cell tumors stratified according to IGCCCG (International Germ Cell Cancer Collaborative Group) risk factors treated with first-line therapy with curative intent. “This is the first study to look at conditional survival with risk stratification. These were unselected real-world data from over 2 decades of clinical practice,” said lead author Jenny Ko, MD, of the British Columbia Cancer Agency, Abbotsford, Canada. “The data support no further routine surveillance CT scans beyond 2 years post diagnosis and treatment [in surviving patients],” she stated.

Germ cell tumor is an uncommon tumor, but it is increasing in incidence, explained Dr. Ko. Poor-risk patients have the potential for cure, since the disease is considered chemosensitive. IGCCCG risk factors stratify patients, “but it is unknown how the initial risk changes over time for those patients who survive and stay disease-free after curative treatment (ie, conditional survival),” she explained.

Study Details

The retrospective study included 942 patients with metastatic testicular germ cell tumors diagnosed between 1990 and 2012 and treated with curative intent at five tertiary centers. The primary endpoints were 2-year conditional overall survival and 2-year conditional disease-free survival assessed for the subsequent 2 years from a given timepoint after the initial diagnosis.

Of the 942 patients, 63% had favorable-risk disease, 19% had intermediate-risk disease, and 16% had poor-risk disease (2% missing data). Of this group, all patients had at least 2 years of follow-up data, and at least 5 years of follow-up was available for 690 patients.

Median age was 31 years; 76% were younger than 40 years of age; about 50% had stage II disease and 50% had stage III disease; and approximately 25% had seminomatous tumors. Most patients received chemotherapy as primary curative treatment. Eighteen percent had disease recurrence, upon which most patients received additional chemotherapy and sometimes underwent other modalities of therapy including autologous stem cell support, radiation therapy, and surgery.

Survival Outcomes

Two-year conditional overall survival changed little in the IGCCCG favorable- and intermediate-risk groups, but in the poor-risk group, it went from 71% at baseline to 93% at 24 months. In poor-risk patients, 2-year conditional disease-free survival was 55% at baseline and 98% at 24 months.

In favorable-risk patients, 2-year conditional overall survival was 97% at baseline and 99% at 24 months, and in intermediate-risk patients, it was 94% and 99%, respectively.

Five-year overall survival was 95% in favorable-risk patients, 93% in intermediate-risk patients, and 64% in poor-risk patients. These results compare favorably with 5-year overall survival in the IGCCCG study: 89%, 75%, and 41%, respectively, showing that over time, survival has improved in the modern era.

Baseline IGCCCG risk stratification was not associated with long-term conditional overall survival or conditional disease-free survival in patients who survived more than 2 years post therapy. No significant differences in survival were noted between seminoma and nonseminoma tumors.

“These findings have implications for survivorship; for counseling patients; for applying for life, disability, or medical insurance; and for determining the appropriate surveillance imaging schedule, as these patients are young and with few comorbidities,” stated Dr. Ko.

The Indiana University Experience

This study sought to identify prognostic factors in a contemporary cohort of patients with metastatic testicular germ cell tumors treated at Indiana University from 1998 to 2012. The retrospective analysis identified 1,341 patients with testicular germ cell tumors treated consecutively over that period; 615 patients who received initial chemotherapy with cisplatin-based combinations were the focus of study. Median follow-up was 60 months.

“There are limited survival data for patients with metastatic germ cell tumors treated with contemporary cisplatin-based combination chemotherapy. Our results indicate superior progression-free survival and overall survival in the modern era compared to previous data from the IGCCCG in the 1990s. We saw this in all risk groups, but particularly in poor-risk patients,” said first author Nabil Adra, MD, of Indiana University School of Medicine, Indianapolis.

Outcomes Stratified by Risk

In poor-risk patients, 5-year progression-free survival improved from 41% in IGCCCG to 51% in our results, and 5-year overall survival improved from 48% in IGCCCG to 72% in our data.

In favorable-risk patients, 5-year progression-free survival was reported at 88% between 1975 and 1990 by IGCCCG, whereas it improved to 90% in the Indiana experience. Five-year overall survival was 91% and 97%, respectively.

In intermediate-risk patients, 5-year progression-free survival was 75% between 1975 and 1990 and improved to 84% in the Indiana experience. Five-year overall survival was 79% and 93%, respectively.

Further, intermediate-risk patients treated with three cycles of bleomycin, etoposide, and cisplatin had similar survival rates as patients who received four cycles of this regimen followed by one cycle of etoposide and cisplatin.

“Our results suggest that four cycles of bleomycin, etoposide, and cisplatin—the current standard of care—probably represents an overtreatment in a substantial number of intermediate-risk patients. This retrospective study suggests that these patients can be treated with three cycles of bleomycin, etoposide, and cisplatin plus one cycle of etoposide and cis­platin without jeopardizing outcome,” Dr. Adra said.

He attributed the improvement in overall survival in all-risk patients to successful salvage therapy and better supportive care.

On a more sober note, “Patients with primary mediastinal non-seminomatous germ cell tumors continue to have poor outcomes and pose a therapeutic challenge due to lack of effective salvage therapy,” he said. ■

Disclosure: Drs. Ko and Adra reported no potential conflicts of interest.

References

1. Ko JJ, Bernard BD, Tran B, et al: Conditional survival of patients with metastatic testicular germ cell tumors treated with first-line curative therapy. 2016 Genitourinary Cancers Symposium. Abstract 472. Presented January 8, 2016.
2. Adra N, Ku KP, Kaira M, et al: Survival outcomes of patients with metastatic germ cell tumor treated from 1998 to 2012: The Indiana University experience. 2016 Genitourinary Cancers Symposium. Abstract 491. Presented January 8, 2016.