This patient should be treated for a gastrointestinal malignancy. He has a moderately differentiated adenocarcinoma of unknown primary site, with most of the disease occurring below the diaphragm. When adenocarcinoma of unknown primary site presents in a pattern predominantly below the diaphragm, even when upper endoscopy and colonoscopy findings are normal, empiric treatment for a gastrointestinal malignancy is appropriate.

Platinum-based chemotherapy regimens such as carboplatin plus paclitaxel or cisplatin plus etoposide would be reasonable for treating patients with a poorly differentiated cancer of unknown primary site (CUP), such as a germ cell (testicular) tumor. This patient's biopsy findings, which show adenocarcinoma with moderately differentiated histology, do not support empiric treatment for germ cell cancer.

Empiric lung cancer regimens may be used to treat patients with CUP occurring above the diaphragm. Because this patient has no evidence of involvement of the lungs, treatment using a lung cancer paradigm is not indicated.

Platinum-based chemotherapy regimens such as carboplatin plus paclitaxel or cisplatin plus etoposide would be reasonable for treating patients with a poorly differentiated neuroendocrine CUP. However, this patient's biopsy findings do not support a diagnosis of neuroendocrine cancer.

Antiandrogen therapy, which may have potential activity against prostate cancer, may be considered in male patients with extensive bone metastases, but that is not the case in this patient.