Volume 82, February 2023, 102316Author links open overlay panelAbstractBackground

Cancers of unknown primary (CUP), a group of heterogenous metastatic cancers lacking a known primary site, have poor prognosis. This study compared survival of CUP by histologic type, patient characteristics, and treatment in the U.S. Military Health System (MHS), which provides universal care to its members.

Methods

Patients histologically diagnosed with CUP were identified from the U.S. Department of Defense (DoD)’s Automated Central Tumor Registry. Median survival with 95 % confidence intervals was calculated for demographic and treatment variables by histologic type. A multivariable accelerated failure time model estimated time ratios and 95 % confidence intervals.

Results

The study included 3358 CUP patients. The most prevalent CUP in this study was well- and moderately-differentiated adenocarcinomas. Median survival varied by histologic type with squamous cell carcinoma having the longest at 25.1 months and poorly-differentiated carcinomas having the shortest at 3.0 months. For each histologic type, survival was generally similar by sex and active-duty status although women with well- and moderately-differentiated adenocarcinoma had longer survival than their male counterparts. Younger patients tended to have longer survival than those aged 65 years or older. Generally, there were no racial differences in survival except poorer survival for Black patients than White patients in the group of other histologic types. Patients with chemotherapy and radiation treatment generally had improved survival whereas patients with squamous cell carcinoma who received chemotherapy had shorter survival than those without.

Conclusion

Survival generally did not differ between racial groups, which may be related to equal healthcare access despite racial background. Further studies are warranted to better understand how survival in the MHS compares with that in the general U.S. population.

Section snippetsBackground

Cancers of unknown primary (CUP) are a group of heterogenous metastatic cancers lacking a known primary origin site after complete evaluation and have a poor prognosis [1]. It is estimated that 1.6 % of all new cancers diagnosed in 2022 will be from unspecified primary sites which comprise 7.8 % of cancer deaths [2]. While the incidence has been decreasing over the last several decades [1], [3], the prognosis for CUP patients remains poor, with median survival under a year [1], [4], [5], [6],

Data source, study population, and study variables

The data were obtained from the DoD’s Automated Central Tumor Registry (ACTUR), which was established in 1986 to collect and track all cancer patients among MHS beneficiaries diagnosed or treated at military treatment facilities. Patients aged 18 years or older histologically or cytologically diagnosed with CUP (ICD-O-3 code 80.9) from 1987 through 2013 were eligible. Patients without a histologic diagnosis (n = 275) were excluded. To reduce potential inclusion of metastases from a previous or

Results

Table 1 shows the demographic and tumor characteristics of the study population. The study included 3358 patients aged 18 years or older diagnosed with CUP from 1987 through 2013, of whom almost half (49.8 %) were 40–64 years old, 44.0 % were 65 years or older, and 6.2 % were 18–39 years old. Men comprised 60.2 % of the study population. Most patients were White (78.9 %) with a smaller percent being Black (11.0 %) or other races (7.5 %). Active-duty patients formed 6.2 % of the population.

Discussion

This study found that the most prevalent CUP in the MHS was well- and moderately-differentiated adenocarcinomas. All histologic types had poor survival with the median OS of 4.8 months. Survival varied by histologic type with squamous cell carcinoma having the best and poorly-differentiated carcinomas having the worst. Survival was generally similar by sex, race, and active-duty status except longer OS for younger patients than those aged 65 years or older and for women with adenocarcinoma than

CRediT authorship contribution statement

Julie A. Bytnar: Conceptulization, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing. Jie Lin: Formal analysis, Methodology, Writing – review & editing. Joel T. Moncur: Formal analysis, Methodology, Writing – review & editing. Craig D. Shriver: Supervision, Conceptualization, Formal analysis, Funding acquisition, Writing – review & editing. Kangmin Zhu: Supervision, Conceptualization, Data curation, Formal analysis, Investigation, Methodology,

Conflict of interest

The authors declare no conflicts of interest.

Acknowledgments

This project was supported by the John P. Murtha Cancer Research Program, Department of Surgery, Uniformed Services University of the Health Sciences under the auspices of the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

Disclaimers

The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of the Uniformed Services University of the Health Sciences (USUHS), the Henry M. Jackson Foundation for the

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