Abstract
PURPOSEThe classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990.MATERIALS AND METHODSData on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set.RESULTSCompared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update).CONCLUSIONThe IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.
Highlights
About half of the patients with nonseminomatous germ cell tumors (GCT) present with metastatic disease
Compared with the original International Germ Cell Cancer Collaborative Group (IGCCCG) publication, 5-year progression-free survival (PFS) remained similar in patients with good prognosis with 89% (87%-91%) versus 90%, but the 5-year overall survival (OS) increased from 92% (90%94%) to 96% (95%-96%)
In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%)
Summary
About half of the patients with nonseminomatous germ cell tumors (GCT) (nonseminomatous germ cell tumors [NSGCT]) present with metastatic disease. Their cure rate is highly variable depending on histology, primary tumor location, tumor marker levels, and metastatic sites. In recent years, improved survival rates in metastatic NSGCT have been reported, possibly because of improved diagnostic tools, improved supportive care, introduction of the IGCCCG prognostic classification and tailored treatment according to this classification, better guideline adherence with standard use of cisplatin- and etoposide-based first-line treatments, more stringent use of postchemotherapy surgery, improved salvage treatments, and centralized management at dedicated expert centers or a combination of these factors.[2,3,4,5,6,7]. Patients included in the original IGCCCG analysis were treated between 1975 and 1990, and not all had received cisplatin or etoposide, which would be the treatment backbone for metastatic NSGCT today.[3,7]
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