Cancer of unknown primary patients with midline nodal distribution: midway between poor and favourable prognosis?

Midline nodal cancer of unknown primary (CUP) has varying definitions and an unclear natural history compared to that of extragonadal germ cell cancer (EGCC) and neuroendocrine tumors.

We systematically reviewed all published series of patients with midline nodal CUP using three distinct definitions and presented our own retrospective cohort.

Sixty four fit patients (median age 64) with poorly differentiated carcinoma or adenocarcinoma in midline nodal areas were treated from 1998 to 2008 at our center. Only two patients had elevated serum germ cell markers. Forty-eight percentage of patients responded to platinum-based chemotherapy (CR 11%). The median survival was 12 months (2-year survival 18%). Good PS (Hazard Ratio HR 0.287, p=0.058) and administration of platinum (HR 0.340, p=0.08) predicted for more favourable outcome. A subgroup of 15 male patients selected with stricter criteria had a CR rate of 33% and median survival of 18 months (2-year survival 24%). We identified 10 series of midline nodal CUP patients defined with discordant criteria. Despite high response rates (35-65%) to platinum chemotherapy, the median survival clustered around 12 months. Predictive factors for superior survival were low tumor bulk, patient fitness, female gender, carcinomatous histology, and absence of visceral metastases. There were differences between midline nodal CUP patients and EGCC as well as neuroendocrine tumors (age, tumor markers, response to therapy, long-term survival).

Midline nodal CUP patients are poorly defined, fare less well than EGCC or neuroendocrine cancer and probably constitute a heterogeneous entity with a minority harbouring atypical germ cell cancer.