Abstract
This case-control study assesses the association between teratoma in the primary tumor or postchemotherapy resections and survival outcomes.
Approximately 30% of patients with nonseminomatous germ cell tumors (GCTs) have residual disease on imaging after first-line cisplatin-based chemotherapy. In patients with residual nonretroperitoneal (non-RP) disease without any residual RP disease, the presence of teratoma in the primary site has been associated with a higher rate of teratoma in postchemotherapy residual non-RP disease.1 Additionally, the presence of teratoma in the primary tumor or in postchemotherapy RP lymph node dissection specimens was found not to be a factor in outcome.2 Clinical outcomes have not been defined for patients with residual non-RP disease without any residual RP disease.
Methods
Patients with metastatic nonseminomatous GCT treated at Indiana University between January 1, 1990, and December 31, 2022, were evaluated. These patients had postchemotherapy residual non-RP disease without residual RP disease. The Indiana University Institutional Review Board deemed this case-control study exempt from review and informed consent. We followed the STROBE reporting guideline.
Primary outcome was the association between the presence of teratoma in the primary tumor or postchemotherapy non-RP resections and survival outcomes in patients with postchemotherapy non-RP residual disease. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Two-sided P < .05 indicated statistical significance for all tests. Data analysis was performed with SAS 9.4 (SAS Institute Inc).
Results
We analyzed 131 male patients with residual non-RP disease after completion of either first-line or salvage chemotherapy. Table 1 lists patient characteristics. The median (range) age at diagnosis of 29 (16-52) years. International Germ Cell Cancer Collaborative Group risk was good in 56 patients (43%), intermediate in 23 patients (17%), and poor in 52 patients (40%). Seventy-six patients (58%) had teratoma in the primary tumor. Fifty-eight patients (44%) had at least 1 postchemotherapy non-RP surgical specimen with teratomatous components.
Table 1. Patient Characteristics.
| Characteristic | Patients, No. (%) (N = 131) |
|---|---|
| Age, median (range), y | 29 (16-52) |
| Pre–first-line chemotherapy: AFP, median (range), ng/mL | 66.7 (0.9-467 000) |
| Pre–first-line chemotherapy: human chorionic gonadotropin, median (range), mlU/mL | 692 (0.5-500 000) |
| Primary cancer site | |
| Testis | 130 (99) |
| Retroperitoneum | 1 (1) |
| Teratoma in orchiectomy | |
| Yes | 76 (58) |
| No | 55 (42) |
| Orchiectomy predominant histological subtype | |
| Embryonal carcinoma | 45 (35) |
| Mixed | 34 (26) |
| Choriocarcinoma | 19 (15) |
| Teratoma | 15 (12) |
| Yolk sac tumor | 14 (11) |
| Seminoma | 2 (2) |
| Necrosis | 2 (2) |
| IGCCCG risk | |
| Good | 56 (43) |
| Intermediate | 23 (17) |
| Poor | 52 (40) |
| Metastasis sites | |
| Pulmonary | 36 (28) |
| Brain | 26 (20) |
| Retroperitoneum | 19 (15) |
| Liver | 11 (8) |
| Mediastinal lymph nodes | 10 (8) |
| Bone | 10 (8) |
| Retrocrural lymph nodes | 8 (6) |
| Pelvic lymph nodes | 2 (2) |
| Supraclavicular or cervical lymph nodes | 1 (1) |
| First-line chemotherapy | |
| 4 Cycles of bleomycin, etoposide, and cisplatin | 68 (52) |
| 3 Cycles of bleomycin, etoposide, and cisplatin | 29 (22) |
| 4 Cycles of etoposide and cisplatin | 10 (8) |
| 4 Cycles of etoposide, ifosfamide, and cisplatin | 7 (5) |
| Other | 17 (13) |
| Surgical resection setting | |
| Post–first-line chemotherapy | 106 (81) |
| Postsalvage chemotherapy | 20 (16) |
| Both | 5 (4) |
Abbreviations: AFP, α-fetoprotein; IGCCCG, International Germ Cell Cancer Collaborative Group.
SI conversion factors: To convert AFP to microgram per liter, multiply by 1.0. To convert chorionic gonadotropin to international units per liter, multiply by 1.
Median (range) follow-up was 3.16 (0.2-29.4) years. Two-year PFS was 59% (95% CI, 45%-71%) for patients with teratoma vs 54% (95% CI, 38%-67%; P = .42) for patients without teratoma in the primary site. Two-year OS for patients with teratoma in the primary site was 85% (95% CI, 73%-92%) vs 70% for patients without (95% CI, 54%-81%; P = .18). Two-year PFS was 89% (95% CI, 70%-96%) for patients with teratoma, 62% (95% CI, 33%-76%) for patients with necrosis, and 37% (95% CI, 21%-52%; P = .03) for patients with active GCT in any postchemotherapy non-RP site, and 2-year OS rates were 100% (95% CI, 100%-100%), 75% (95% CI, 52%-88%), and 69% (95% CI, 51%-82%; P = .03), respectively. Eight of 41 patients with necrosis initially had resection of dominant residual disease followed by observation, although all 8 patients eventually progressed. Table 2 shows the 2-year PFS and OS rates based on pathology and location of non-RP site.
Table 2. Two-Year Progression-Free Survival (PFS) and Overall Survival (OS) Based on Pathology and Location of Nonretroperitoneal Site.
| Variable | 2-y PFS (95% CI), % | P value | 2-y OS (95% CI), % | P value |
|---|---|---|---|---|
| Teratoma in primary site | ||||
| With teratoma (n = 76) | 59 (45-71) | .42 | 85 (73-92) | .18 |
| Without teratoma (n = 55) | 54 (38-67) | 70 (54-81) | ||
| Postchemotherapy-nonretroperitoneal site residual pathology | ||||
| With teratoma (n = 58) | 89 (70-96) | .03 | 100 (100-100) | .03 |
| With necrosis (n = 41) | 62 (33-76) | 75 (52-88) | ||
| With active GCT (n = 53) | 37 (21-52) | 69 (51-82) | ||
| Postchemotherapy lung resection residual pathology | ||||
| With teratoma (n = 40) | 89 (63-97) | .02 | 100 (100-100) | .005 |
| With necrosis (n = 35) | 57 (33-76) | 74 (48-88) | ||
| With active GCT (n = 22) | 26 (7-52) | 65 (31-85) | ||
| Postchemotherapy brain resection residual pathology | ||||
| With active GCT (n = 17) | 23 (4-52) | NA | 70 (33-89) | NA |
Abbreviations: GCT, germ cell tumor; NA, not applicable.
Discussion
Advancements in testicular GCT treatment have led to a cure for most patients. Unanswered questions remain, however, that may help guide treatment recommendations for subsets of patients. In this study, we observed no association between presence of teratoma in the primary tumor or postchemotherapy residual RP disease resections and survival outcome. Similarly, we found no association between teratoma in the primary tumor or in postchemotherapy non-RP residual disease and inferior survival.
Presence of necrosis in residual disease resections had inferior PFS and OS compared with presence of teratoma. This finding may be explained by 8 patients undergoing resection of the dominant site first. After necrosis was found, other sites of disease were observed but eventually progressed in all 8 patients, potentially contributing to inferior outcomes. The finding of necrosis in a dominant lesion of disease may be reassuring, although there is still the potential for other sites of residual disease to eventually progress. These patients may benefit from a multidisciplinary discussion in a high-volume testicular cancer center.
This study was limited by its retrospective nature with the potential for selection bias.
Data Sharing Statement
References
- 1.King JM, Cheng M, Kesler K, et al. Management of residual nonretroperitoneal disease in postchemotherapy nonseminomatous germ-cell tumors. J Clin Oncol. 2023;41(23):3939-3944. doi: 10.1200/JCO.22.02205 [DOI] [PubMed] [Google Scholar]
- 2.Taza F, Chovanec M, Snavely A, et al. Prognostic value of teratoma in primary tumor and postchemotherapy retroperitoneal lymph node dissection specimens in patients with metastatic germ-cell tumor. J Clin Oncol. 2020;38(12):1338-1345. doi: 10.1200/JCO.19.02569 [DOI] [PMC free article] [PubMed] [Google Scholar]
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Data Sharing Statement