Detection of Relapse by Tumor Markers Versus Imaging in Children and Adolescents With Nongerminomatous Malignant Germ Cell Tumors: A Report From the Children’s Oncology Group

Abstract

PURPOSE To investigate relapse detection methods among children and adolescents with nongerminomatous malignant germ cell tumors (MGCTs) and to determine whether tumor markers alone might be sufficient for surveillance. METHODS We retrospectively reviewed all patients enrolled in a phase III, single-arm trial for low-risk and intermediate-risk MGCTs. The method used to detect relapse was assessed based on case report forms, tumor markers, imaging, and pathology reports. Relapses were classified into one of two categories on the basis of whether they were (1) detectable by tumor marker elevation or (2) not detectable by tumor markers. RESULTS A total of 302 patients were enrolled, and 284 patients had complete data for review. Seven patients had normal tumor markers at initial diagnosis, and none experienced a relapse. At a median follow-up of 5.3 years, 48 patients (16.9%) had experienced a relapse. After central review, 47 of 48 relapses (98%) were detected by tumor marker elevation. Of the 47 patients, 16 (33.3%) had abnormal tumor markers with normal/unknown imaging, 31 patients (64.6%) had abnormal tumor markers with abnormal imaging, and one patient (2.1%) had abnormal imaging with unknown marker levels at relapse. CONCLUSION Tumor marker elevation is a highly sensitive method of relapse surveillance, at least among children and adolescents with tumor marker elevation at initial diagnosis. Eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCT.

Should we reduce routine surveillance imaging in pediatric germ cell tumors?

“…Fonseca et al 4 . reported a very high sensitivity of STMs in a specific subset of the disease, and our study had a similar (group B) yet not quite as high result (98% vs. 94%).…”

“…We performed the analyses in three different sets of patients: group A, including all types of malignant GCTs at all sites, both patients with/without elevated STMs at diagnosis, all types of relapse (malignant as well as teratomatous GCT); group B, similar to the one reported by Fonseca et al., 4 excluding dysgerminoma histology, stage IV MOGCT at diagnosis and relapses with histology showing teratoma with/without malignant transformation; group C, including only malignant GCTs with pathological STMs at diagnosis (Figure 1).…”

“…We reconsidered relapses amongst the patients enrolled in the TCGM‐AIEOP 2004 Study to evaluate the site of relapse and the method used to detect these, with the aim of evaluating whether it was possible to reduce radiological exposure. We also compared our results with those published by the Children's Oncology Group 4 …”

Diagnostic, Prognostic and Predictive Markers in Pediatric Germ Cell Tumors—Past, Present and Future

“…At relapse, 39 patients (81%) had AFP elevation, one (2%) had β-hCG elevation, seven (15%) had both tumor markers elevated and one did not have available tumor marker data. The COG researchers concluded that eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCTs [46] In contrast are the conclusions of the last study carried out by Chakiryan et al The purpose of this study was to conduct a systematic review of the currently available evidence evaluating the reliability of serum tumor markers as a test for the diagnosis of recurrence in patients with clinical stage I non-seminomatous embryonic tumors under active supervision. This systematic review was conducted in accordance with PRISMA guidelines, with no language or data restrictions and includes studies that readily identified the tumor marker status of patients with clinical stage I non-seminomatous germ cell tumors who had a recurrence of active surveillance, with marker positivity as the primary outcome at the time of recurrence.…”

“…At relapse, 39 patients (81%) had AFP elevation, one (2%) had β-hCG elevation, seven (15%) had both tumor markers elevated and one did not have available tumor marker data. The COG researchers concluded that eliminating exposure to imaging with ionizing radiation may enhance the safety of relapse surveillance in patients treated for MGCTs [ 46 ]…”