LDH isozyme is a tetramer of two subunits, H chain and M chain, and is present in all living tissue. Five types of molecular forms characterize the LDH pattern, and tumor tissues relatively consist LDH-4 and LDH-5, composed with a high ratio of the M chain, compared to normal tissues. This study analyzed whether between LDH isozyme would be a prognostic predictor of metastatic renal cell carcinoma (mRCC) in the usage of IO combination therapy.

RCC patients diagnosed between 2018 and 2023 were retrospectively reviewed. Patients with clinical records of LDH isozyme values were checked. Isozyme patterns were classified into 6 types, LDH 1-5 dominant and common type, according to the most composed molecular form.

mRCC patients treated with IO combination therapy were retrospectively reviewed. 58 patients were identified with suitable data. Median age was 72 years old (48-75). pT1 was seen in 12 cases, pT2 in 10, pT3 in 26, and pT4 in 10. Pathological grade 2 were 15 cases, G3 in 31, and G4 in 12. As for the IMDC risk, favourable was 8 cases (13.8%), intermediate in 29 (50%) and poor in 21 (36.2%). Median LDH was 168 IU/L (110-465), and isozyme dominant pattern were as follows: LDH-2 in 10 cases, LDH-3 in 4, LDH-4 in 8, LDH-5 in 8. 28 cases were common type, and no cases showed LDH-1 dominant. 31 cases were treated with Nivolumab + Ipilimumab, 16 cases with Pembrolizumab + Lenvatinib, 11 cases with Nivolumab + Cabozantinib. Median follow-up period was 23 months (6-48). No significant correlation was seen between pathological grade or pT stage and LDH isozyme pattern before starting systemic therapy. LDH isozyme common pattern showed an improved overall response rate (ORR) of 54%, whereas elevated LDH isozyme patterns showed an ORR of 23%, significantly associated with poor progression free survival.

LDH common isozyme pattern had an improved ORR compared to elevated LDH pattern, proposing as a prognostic predictor of mCRCC in usage of IO combination therapy.