Biomarker in prostate cancerHuman tissue Kallikreins: Blood levels and response to radiotherapy in intermediate risk prostate cancer

ObjectivesKallikreins are serine proteases over expressed in many malignancies. In this study, we measure changes in serum kallikrein (KLKs) levels during intensity-modulated radiotherapy (IMRT) in prostate cancer patients, and find potential correlations between serum kallikrein level and normal tissues toxicity during radiation.MethodsForty-nine patients with prostate cancer were recruited as follows: group 1, definitive standard fractionation IMRT (78 Gy in 39 fractions, n = 15); group 2, definitive hypofractionated IMRT (60 Gy in 20 fractions, n = 15); and group 3, IMRT postprostatectomy (66 Gy in 33 fractions, n = 19). Patients treated with definitive radiation therapy were intermediate risk. Blood samples were collected at baseline and quarterly during IMRT and at each follow-up visit. Acute toxicity was graded weekly during radiotherapy using CTC-AE v4.0 criteria. Multiplexed immunoassays were used to quantify total, free, and intact Prostate Specific Antigen (PSA), as well as Kallikreins 2, 4, 6, and 11.ResultsThe serum kallikreins, PSA (total, free and intact), KLK2, 6, and 11 change significantly after definitive radiotherapy. KLK2 and intact PSA decrease as fast as two weeks after initiation of radiation, while the first significant decrease in total and free PSA is noted only at the completion of radiation. KLK6 and KLK11 surge temporarily during radiation therapy and decrease below baseline levels at 8 weeks and 12 months, respectively after completion of radiation. KLK4 levels did not change with radiation. There was no correlation between GU or GI toxicities and serum kallikreins.ConclusionsPSA, KLK2, 6, and 11, change significantly after definitive prostate radiotherapy, though KLK2 and PSA decrease by the end of the radiation course while KLK6 and KLK11 decrease significantly starting at 2 and 12 months, respectively, after radiation. There was no correlation between GU or GI toxicities and serum kallikreins.