Abstract
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Aim: Partial neuroendocrine differentiation is common in prostate cancer (PCa), especially in high risk PCa with a Gleason-Score 8-10 and could affect PSMA-expression and radio-sensitivity. Aim of this work was to evaluate possible predictive lab markers for 177Lu-(prostate specific membrane antigen) PSMA-617-RLT (radioligand therapy): Prostate specific antigen (PSA) as a secretory marker of prostate cancer cells, Chromogranin A as marker for neuroendocrine cells and lactate dehydrogenase (LDH) as a marker for cell turnover.
Methods: 100 patients with metastasized castration resistant prostate cancer (mCRPC) and PSMA-RLT with treatment activities from 6.0 to 9.3 GBq Lu-177 were selected respectively. PSA, Chromogranin A and LDH were assessed before each cycle of PSMA-RLT and for restaging. To assess tumor uptake, post-therapeutic scintigraphy was evaluated visually regarding quantitative tumor uptake and its homogeneity.
Results: In total, 211 cycles of 177Lu-PSMA therapy were evaluated. 35 patients had partial remission (PR), 16 patients stable disease (SD), 15 patients mixed response (MR) and 36 patients progression of disease (PD). All patients with partial remission had a normal baseline LDH and in majority a PSA <200 ng/ml. Heterogeneous PSMA expression was closely related to MR. Patients with PD often had Chromogranin A > 168 (normal range <84.6) or relevantly elevated LDH, which was a better predictor of response than PSA. Intense tumor uptake (uptake > salivary glands in the 24h p.i. emission scan) was a prerequisite to achieve PR, but there were also several patients with PD despite high tumor uptake, indicating additional resistance mechanisms beyond tumor-dose.
Conclusions: Patients with baseline PSA up to 200 ng/ml, normal to slightly elevated LDH, normal to slightly elevated Chromogranin-A and a homogenously intense uptake of the radiopharmaceutical are most promising to benefit from PSMA-RLT. PSA values >200ng/ml, relevantly elevated LDH or Chromogranin-A values, insufficient or heterogeneous tumor uptake are negative prognostic values indicating an elevated risk for non-response.