Immunohistochemistry on the primary tumor for PSMA-expression might predict the detection of biochemical recurrence with ⁶⁸Ga-PSMA-11-PET.

Objectives: Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high PSA levels (> 3 ng/ml), only 90% of the PSMA-PET scans are positive, probably due to patients with a PSMA-negative PCa. It was the aim to assess whether PSMA-expression of the primary tumor on immunohistochemistry (IHC) can predict the PSMA-PET positivity for BCR.

Methods: Retrospective, ethically approved, single center analysis of patients that underwent 68Ga-PSMA-11-PET for BCR after RPE between April 2016 and December 2018, with tumor specimens available for PSMA-IHC. Clinical information (age, PSA-level, previous therapy, Gleason score) and PSMA-IHC of the primary tumor and if available lymph node metastasis (LNM) were collected and correlated with results from PSMA-PET scans (positive/negative), using a multivariate logistic regression analysis.

Results: 120 PSMA-PET scans in 74 patients were available for this analysis. The overall detection rate was 62% (74 in 120 scans), with a mean PSA value at scan time of 1 ng/ml (range 0.05-406 ng/ml). From the clinical factors, only PSA-level and status after antiandrogen therapy (ADT) correlated with PSMA-PET positivity. Percentage PSMA-negative tumor area on IHC (PSMA_%neg) had a significant inverse correlation to PSMA-PET positivity (p< 0.001), while membranous PSMA-expression did not correlate (p=0.73). The specificity of PSMA_%neg above 50% for a negative PSMA-PET was 97% (72/74) and for a PSMA_%neg of 80% or more, 100% (74/74). PSMA-expression was more homogeneous in LNM than in the primary tumor specimens, but a strong positive correlation was found between primary tumor and nodes for both PSMA_%neg (0.841, p<0.001) and PSMA_memb (0.446, p=0.002). Limitations include retrospective design and the low number of negative PSMA-PET scans.

Conclusions: PSMA-negative tumor area was the best predictor of negative PSMA-PET scans, beside PSA-level and ADT. Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA_%neg above 50%.

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