Site-specific cancer deaths in cancer of unknown primary diagnosed with lymph node metastasis may reveal hidden primaries.

Cancer of unknown primary site (CUP) is a fatal cancer ranking among the five most common cancer deaths. CUP is diagnosed through metastases, which are limited to lymph nodes in some patients. Cause-specific survival data could guide the search for hidden primary tumors and help with therapeutic choices. The CUP patients were identified from the Swedish Cancer Registry between 1987 and 2008; 1,444 patients had only lymph node metastasis of defined histology (adenocarcinoma, squamous cell or undifferentiated). Site-specific cancer deaths were analyzed by lymph node location and histology. Kaplan-Meier survival curves were compared with metastatic primary cancer at related sites. Among the patients with metastasis to head and neck lymph nodes, 117 (59.1% of the specific cancer deaths) died of lung tumors. Patients with axillary lymph node metastasis died of lung and breast tumors in equal proportions (40.2% each). Also, squamous cell CUP in head and neck lymph nodes was mainly associated with lung tumor deaths (53.1%). With a few exceptions, survival of CUP patients with lymph node metastasis was indistinguishable from survival of patients with metastatic primary cancer originating from the organs drained by those nodes. The association between lymph node CUP metastases with cancer deaths in the drained organ and the superimposable survival kinetics suggests that drained organs host hidden primaries. Importantly, half of all site-specific cancer deaths (266/530) were due to lung tumors. Thus, an intense search should be mounted to find lung cancer in CUP patients with lymph node metastases.

Survival in cancer of unknown primary site: population-based analysis by site and histology.

BACKGROUND: Cancer of unknown primary (CUP) is diagnosed at a metastatic stage, conferring an unfavorable prognosis. The natural history of the disease is poorly understood, which complicates diagnosis, treatment and follow-up. Population-based survival data are lacking regarding location and histology of metastases. PATIENTS AND METHODS: From the Swedish Cancer Registry, 18 911 CUP patients were identified between years 1987 and 2008. Survival was analyzed by Kaplan-Meier survival curves and Cox regression. RESULTS: Adenocarcinoma accounted for 70% of all extranodal cases with a 12-month survival of 17% and the median survival of 3 months. Adenocarcinoma was also the most common histology (33.4%) when metastases were limited to lymph nodes, with a 12-month survival of 41% and median survival of 8 months. For extranodal metastases, the extremes in survival were small intestinal cancer with poor prognosis and mediastinal cancer with favorable prognosis. For nodal metastases, patients affected in the head and neck, axillary and inguinal regions had the best prognosis and those with abdominal and intrapelvic metastases the worst prognosis. CONCLUSIONS: The present data underline the importance of histology and location of metastasis in assisting clinical decision making: hazard ratios differed by a factor of five among extranodal and nodal metastases.

Cancer of unknown primary (CUP): does cause of death and family history implicate hidden phenotypically changed primaries?

BACKGROUND: Cancer of unknown primary (CUP) is diagnosed at the metastatic stage. We aimed to identify hidden primary cancers in CUP patients by comparison with cancers in family members. We take use of the fact that the cause of death in CUP patients is often coded as the cancer in the organ of fatal metastasis. PATIENTS AND METHODS: Forty-one thousand five hundred and twenty-three CUP patients were identified in the Swedish Family-Cancer Database, and relative risks (RRs) were calculated for cancer in offspring when family members were diagnosed with CUP and died of the cancer diagnosed in offspring. RESULTS: The RR for lung cancer in offspring was 1.85 when a family member was diagnosed with CUP and died of lung cancer. Significant familial associations were found for seven other cancers. Many familial associations were also significant when offspring CUP patients died of the cancer diagnosed in family members. CONCLUSIONS: The cause of death after CUP diagnosis frequently matched the cancer found in a family member, suggesting that the CUP had originated in that tissue. The metastasis had probably undergone a phenotypic change, complicating pathological tissue assignment. These novel data suggest that some CUP cases are phenotypically modified primary cancers rather than cancers of unknown primaries.