Treatable Subsets in Cancer of Unknown Primary Origin

Abstract

The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1-50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom β β β β-subunit of human chorionic gonadotropin (β β β β-HCG) was elevated more than 10 mIU/ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of β β β β-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.Key words: Cancer of unknown primary -Chemotherapy -Chemosensitive subgroups -β-HCGThe development of imaging procedures, such as ultrasonography, computed tomography, and magnetic resonance imaging, has enabled the detection of the site of primary cancers, as well as metastatic sites. Moreover, immunohistochemical studies were introduced into routine clinical oncology practice recently and have significantly increased the probability of identifying the likely underlying tumor type.1) In spite of these notable advances, the primary site of cancer can still not be determined in approximately 5-10% of all cancer patients.2) As a result, these patients are diagnosed as having "cancer of unknown primary" site (CUP). Accordingly, CUP, by its nature, is extremely heterogeneous in clinical presentation, histologic appearance, and natural history, and there is no standard treatment for CUP. Although reports of patients with CUP have indicated poor prognosis, with overall survival duration of 5-11 months from diagnosis of CUP, [3][4][5] several favorable prognostic factors for chemotherapeutic response have been proposed and the treatment results of patients with such factors were markedly better. 6) However, there is very little information concerning Japanese patients with CUP.To establish such treatable subsets and to identify further prognostic factors predictive of positive responses to chemotherapy, Japanese patients with CUP were retrospectively analyzed after appropriate clinical and pathological exclusion of primary tumors, according to current diagnostic recommendations.

Cancer of unknown primary: clinicopathologic correlations

“…Systematic analysis of treatment responses and survival results in this heterogeneous group of patients is problematic, and the optimal management of CUP has become more complex with the recognition that some patients benefit greatly from therapy (5, 13–15). Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined, whereas empiric therapy is an option for the remaining patients (5).…”

“…In the past, various antitumor therapeutic trials have had a negligible effect on survival, encouraging a nihilistic approach to these patients who are commonly stereotyped as elderly, debilitated persons with metastases at multiple visceral sites. Nevertheless, subsets of CUP patients have been identified by defining several clinical syndromes associated with a clinical response to therapy (4, 5, 13–15). Specialized pathology techniques, e.g.…”

A long-term survivor of repeated inguinal nodes recurrence of papillary serous adenocarcinoma of CUP: case report

“…Although the histologic features of our case presented a papillary configuration and psammoma bodies in all of the surgical specimens, no primary site was found in the body or in the ovaries. Taking into account the fact that the epithelial layer of the ovary and the peritoneum share a common origin from the coelomic epithelium embryonically and that repeated elevations of the serum CA19-9 level occurred whenever metastasis had occurred in our case, it is plausible that papillary serous carcinoma of the peritoneum is an analog with ovarian carcinoma or an extraovarian primary peritoneal carcinoma [ 3 , 14 ]. Clinical experiences in treating patients with inguinal nodes metastases of female peritoneal papillary serous carcinomas have been reported infrequently and there is a lack of a standard chemotherapeutic regimen for this unusual and poor prognostic disease [ 2 , 15 ].…”

“…Clinical experiences in treating patients with inguinal nodes metastases of female peritoneal papillary serous carcinomas have been reported infrequently and there is a lack of a standard chemotherapeutic regimen for this unusual and poor prognostic disease [ 2 , 15 ]. Cisplatin-based chemotherapy might be a choice in our case, given that favorable response rates [ 3 , 14 , 15 ] have been reported in female peritoneal papillary serous carcinoma cases if metastases outside the peritoneal cavity have not been present. However, we chose modified FAM, because a regimen including 5-FU, ADM and MMC have shown some valuable activity in many adenocarcinomas of the gastrointestinal tract, pancreas, lung and breast, etc.…”

Unknown primary

“…Sumi et al retrospectively studied 50 patients to determine treatable subsets in the cancer of unknown primary. They concluded that patients with poorly differentiated carcinomas in whom beta-HCG was elevated and female patients with peritoneal adenocarcinomatosis achieved high response rates with platinumbased chemotherapy, 83.3 and 80%, respectively, compared with only 15.3% in the remaining patients [84].…”