Prognostic role of T3/T4 ratio in metastatic renal cell carcinoma (mRCC): Preliminary results of the threeFOUR multicenter study (Meet-Uro 14)

Background: Thyroid hormones metabolism can be altered in patients (pts) with chronic diseases and/or undergoing cancer treatments. The prognostic role of T3/T4 ratio has been investigated in metastatic colorectal cancer pts in whom a high T3/T4 ratio predicted longer survival. No data are available in mRCC. Methods: We retrospectively reviewed the clinical charts of pts with mRCC treated in first line for metastatic disease at 8 Italian Oncology Units before March 2017, having at least one response assessment and baseline complete thyroid panel data available. T3/T4 was calculated as the ratio of the two value of hormones and categorized in tertiles. Results: We identified 96 pts, median age 62 years (range 27-82), 72% males. Sunitinib wad administered in 56% of pts, pazopanib in 38%, nivolumab and ipilimumab in 6%. According to Heng Score, 33% of the pts were at favorable risk, 58% at intermediate risk, 9% at poor risk. With a median follow-up time of 42.8 months, median PFS was 24.8 months, estimated median OS was 71.6 months. Tertile distribution of patients was 36.4% in the high, 29.1% in the medium and 34.5% in the low subgroup. A baseline high tertile value (≥ 0.35) predicted longer PFS (39.4 vs 21.8 1vs 4.5 months, p = 0.01), while median OS has not been reached in the three tertiles, with survival at 24 months being 69.7%, 82.1% and 91.4%, respectively in the low, medium, high group (p = ns). The high T3/T4 ratio is also strongly associated with the chance to achieve a partial or complete response (42.8% vs 39.9% vs 21%, X squared test, p < 0.001). Heng prognostic model retained its prognostic role in this cohort (median OS was 77.1 vs 48.4 vs 22.3 months, p < 0.001, respectively for favorable, intermediate or poor risk group) and also predicted PFS (median PFS 38.2 vs 17.2 vs 8.4 months, p = 0.004). Baseline NLR ≥ 3 predicted shorter OS (46.5 vs 77.1 months, p = 0.02) in the whole group. Conclusions: In our retrospective multicenter experience, a high T3/T4 ratio was associated with longer PFS and a higher probability to respond to the treatment. Median OS had not been reached for all the subgroups, probably due to a favorable patients selection. A longer follow-up is needed to validate the prognostic value of T3/T4 ratio in this cohort.