Evaluation of the efficiency of combination palliative treatment in patients with metastatic clear-cell renal cell carcinoma

Background. Experience with combination treatment, i.e. systemic therapy in combination with palliative surgery, in the treatment of metastatic kidney cancer is very rarely described in world literature.
Objective: to evaluate the efficiency of combination treatment in combination with palliative cytoreductive surgery and targeted therapy and to define optimal indications for combination treatment.

Subjects and methods. Data on 47 patients with metastatic renal cell carcinoma (mRCC) who received systemic (targeted) therapy in combination or after incomplete cytoreduction (iCR) were analyzed in this retrospective study. The proportion of men and women was 72.3 % and 27.7 %, respectively; their ratio was 2.6:1. All the patients (100%) underwent surgical treatment as nephrectomy or kidney resection for primary tumor. In the patients who had received radical treatment in different periods, the median relapse-free survival was 25.3 (0-187) months; the mean follow-up duration in the study was 33.2 (27.4–39.0) months. Out of the histological characteristics of a primary tumor, its Fuhrman grade was studied. Prior to initiation of mRCC therapy, Memorial Sloan Kettering Cancer Center (MSKCC) prognosis groups were assessed; the patients were divided into good (n = 9 (19.1 %)), interim (n = 28 (59.6 %)), and bad (n = 10 (21.3 %)) prognosis groups. Their total somatic status was separately rated using the ECOG scale: 0, (n = 10 (21.3%)), 1 (n = 24 (51.1 %)), and 2, (n = 13 (27.6 %)). The sites of metastases were as follows: the lung (n = 29), bones (n = 18), adrenals (n = 11), recurrence in the removed kidney bed (n = 10), and liver (n = 10). Multiple organ involvements were detected in 22 (46.8 %) patients. There were more than 5 metastases in one organ in 18 (40.0 %) patients and only 15 (33.3 %) were found to have a single focus in one organ. Whether iCR might be used as a separate line treatment was studied. A comparative analysis was made between 2 groups of patients with mRCC: 1) 20 patients who underwent iCR and 2) 27 patients who received systemic therapy (immunotherapy (n = 12), sorafenib (n = 8), and sunitinib (n = 7)). The control points were estimation of overall survival (OS), optimal indications for iCR in patients with mRCC, and time to progression (TTP) during first- and second-line systemic treatment.

Resuts. The median OS duration in Group 1 was longer: 46 months versus 31 months (p = 0.09). TTP was comparable: 9 and 6 months, respectively. Comparison of first-line systemic treatment showed that the median TTP was twice longer (13 and 17 months in the targeted (sorafenib and sunitinib) therapy group than that in the cytokine therapy group (6 months) (p = 0.0174). TTP during second-line therapy was 10 months. Median OS after immunotherapy, sorafenib and sunitinib therapy demonstrated no differences and was 34.2, 36.5, and 39.2 months (р = 0.8). 

Conclusion. This investigation suggests that the comprehensive approach in effective in treating mRCC. iRC may be used as an individual treatment in a certain patient group. However, survival rates in the examined group of patients can be increased only when targeted drugs are necessarily used in both first- and second-line treatment regimens. In spite of the metastatic pattern of RCC, the treatment algorithm for these patients should estimate the possibilities of using palliative cytoreductive treatment since its use may provide a median TTP of as many as 9 months. Just the same, over 30-month survival rates may be obtained when the latter is used in combination with systemic treatment.

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