Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.
Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.
“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.
They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.
“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.
Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.
A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.
The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.
Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.
Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.
A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.
Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).
Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.
Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.
For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.
Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).
Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).
The authors called for further prospective studies of this subset of patients with CUP.
SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.