Date Published: February 20, 2019
Publisher: Public Library of Science
Author(s): Sung Han Kim, Jung Kwon Kim, Eun Young Park, Jungnam Joo, Kang Hyun Lee, Ho Kyung Seo, Jae Young Joung, Jinsoo Chung, Aamir Ahmad.
This study aimed to determine the prognostic factors of progression-free survival (PFS) and overall survival (OS) in non-nephrectomized patients with synchronous metastatic renal cell carcinoma (mRCC) receiving first-line vascular endothelial growth factor (VEGF)-targeted therapy or immunotherapy.
Of 70 patients, 57 (81.4%) were treated with targeted therapy, including 5 (7.1%) with previous immunotherapy and 13 (18.6%) with immunotherapy only. The medical records of patients were retrospectively reviewed and analyzed to determine factors of PFS and OS using the Cox proportional hazards model with a statistical significance p-value <0.05. The median treatment and follow-up periods were 3.9 and 30.9 months, respectively. Disease progression was reported in 90.0% of patients, with an objective response rate and clinical benefit rate of 26.1% and 76.8%, respectively. The lung (77.1%) was the most common site of metastasis. Multivariable analysis showed that poor Heng risk (hazard ratio [HR]: 2.37) and liver metastasis (HR: 2.34) were significant prognostic factors for PFS, and female sex (HR: 2.13), poor Heng risk (HR: 3.14), and liver metastasis (HR: 2.78) were significant prognostic factors for OS (p < 0.05). A subset analysis of risk factors among patients without previous history of immunotherapy also showed poor Heng risk (HR 2.92 and HR 4.24 for PFS) and liver metastasis (HR 2.87 and HR 4.81 for OS) as significant factors for both PFS and OS (p<0.05). Poor Heng risk, sex, and liver metastasis were associated with survival outcomes after first-line systemic therapy in patients with non-nephrectomized synchronous mRCC.
Global statistics suggest that approximately one-third of newly diagnosed cases of renal cell carcinoma (RCC) are detected at an advanced stage or at metastasis; this is known as synchronous metastatic renal cell carcinoma (smRCC] . The prognosis of smRCC is poorer than that of metastatic recurrent RCC initially treated via radical nephrectomy; this is known as metachronous metastatic RCC (mRCC; overall survival [OS]: 4 and 19 months, respectively) . The unfavorable prognosis of smRCC has been attributed to the patient’s poor general condition, which lowers tolerance for the total dose of first-line systemic therapeutic agents required. Moreover, metastatic tumors render patients ineligible for surgery, especially when critical organs are involved.
All study protocols were conducted in accordance with the ethical guidelines of the World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. The medical records of all enrolled patients were de-identified and analyzed anonymously. This study was approved by the Institutional Review Board of the Research Institute and Hospital National Cancer Center (NCC2016-0263). The board waived the requirement for written informed consent.
Of 70 enrolled patients, 52 (74.3%) were treated with targeted therapy only and 13 (18.6%) were treated with immunotherapy only. Five (7.1%) patients who were treated with targeted therapy had history of previous immunotherapy. During a median follow-up period of 30.9 (6.0–30.9) months and a median treatment period of 3.9 (1–60.4) months, disease progression was reported in 90.0% of patients, with an objective response rate and clinical benefit rate of 26.1% and 76.8%, respectively; 5.8% of patients (n = 4) achieved complete remission. Metastasis was detected in a median of two organs with a median primary renal tumor size of 9.4 cm; the lung (77.1%) was the most common site of metastasis, followed by the lymph nodes (37.1%), bone (31.4%), liver (22.9%), and brain (12.1%). Histology results showed that 81.4% (n = 57) and 18.6% (n = 13) were clear cell type and unclassified type, respectively. A sarcomatoid component was observed in 4 (5.7%) patients. In addition, 18 (25.7%) patients had a previous history of immunotherapy, including 17 (94.4%) who were treated with interferon-alpha and 1 (5.6%) who was treated with interleukin, with a median treatment duration of 67.5 (21–452) days (Table 1).
Considering the increase in the number of patients diagnosed with naïve unresectable synchronous mRCC, this study focused on the prognostic factors of PFS and OS during first-line TT and immunotherapy, which helps clinicians potentially identify patients who may respond best to systemic treatment quickly and easily. The present findings showed that poor Heng risk and liver metastasis were significant prognostic factors for both poor PFS and OS, and that female sex was an additional significant factor for poor OS in the multivariable analysis.
The findings of the present study showed that poor Heng risk, female sex, and liver metastases were associated with poor survival outcomes after first-line VEGF-targeted therapy or immunotherapy in patients with naïve, smRCC. Further well-designed prospective studies are warranted to establish the best multidisciplinary therapeutic strategy.