LDH a Predictor for OS in mCRPC Following Radium-223

Maarten Van Der Doelen, MD

In results from a retrospective analysis of 45 Dutch men treated with radium-223 (Xofigo) for metastatic castration resistant prostate cancer (mCRPC), researchers have found that log lactate dehydrogenase (LDH) was the strongest predictor for overall survival (OS).

Compared with a control group of men with an ECOG score of 0 (n = 17), those with low LDH (n = 32) had significantly better OS (hazard ratio [HR], 7.67; 95% CI, 1.75-33.53; P <.01).

Maarten van der Doelen, MD, Radboud University Medical Center, Nijmegen, the Netherlands, presented the results in a poster at the 2017 European Multidisciplinary Meeting on Urological Cancers. Based on these results, he told OncLive that LDH should be part of the routine pre-therapy exam.

“What surprised us was that the LDH levels were important at baseline,” he said. “We thought maybe the alkaline phosphatase levels would be important because that reflects bone metabolism and the load of metastases, but LDH outweighed PSA and alkaline phosphatase at baseline [in predicting] which patients would enjoy a survival benefit.”

“LDH should be included in our baseline lab tests. It’s more valuable than baseline PSA or alkaline phosphatase in these patients,” he added.

van der Doelen and his colleagues evaluated men treated for mCRPC in the Netherlands from September 2013, when the use of radium-223 was approved for mCRPC patients with symptomatic bone metastases, through March 2016. Median follow-up until censoring was 28 months and median age was 71.

The primary endpoint was OS. van der Doelen said researchers hoped to identify which patient characteristics were associated with OS following radium-223 treatment.

Researchers reviewed outcomes in what van der Doelen called “last resort patients” who had been previously treated with regimens that included docetaxel, cabazitaxel (Jevtana), enzalutamide (Xtandi), and/or abiraterone acetate (Zytiga).

“These last resort patients, they don’t benefit with the therapy since they discontinued during the therapy after 2 or 3 cycles,” van der Doelen said. “That’s not the benefit we would like to see with radium therapy, so we started treating those patients a little bit earlier, sometimes even predocetaxel.”

“Then we found out, retrospectively, that these patients do better. In particular, we saw that patients who have good performance status and low LDH levels have a greater survival benefit.”

van der Doelen said this study was not designed to determine a threshold LDH level. He is part of a research team that has begun recruiting patients into a prospective study that would levels for threshold for LDH and alkaline phosphatase.

HR was 10.62 (95% CI, 3.07-36.73; P <.01) for men with an ECOG status of 1 (n = 9). For men with an ECOG score of 2 or 3, HR was 5.67 (95% CI, 1.74-18.47). Men who completed 6 cycles of radium therapy had a median OS of 19.7 months compared with just 5.9 months for men who completed 1 to 5 cycles.

van der Doelen acknowledged the limitations of a retrospective study—confidence intervals are very large, for instance—but he said these results will inform the ongoing prospective study and help researchers develop data to better analyze patients.

van der Doelen, MJ, Kuppen MCP, Jonker MA, et al. Real world lessons for optimal selection of patients with bone metastatic castration-resistant prostate cancer for radium-223 therapy. Presented at: 2017 EMUC Congress; Barcelona, Spain; November 16-19, 2017. Abstract P049.