Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy

Berna C Özdemir; Nicolas Arnold; Achim Fleischmann; Janine Hensel; Irena Klima; Marianna Kruithof-de Julio; Fiona Burkhard; Stefanie Hayoz; Bernhard Kiss; George N Thalmann

doi:10.1016/j.euros.2022.07.005

Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy

Eur Urol Open Sci. 2022 Aug 16:44:1-10. doi: 10.1016/j.euros.2022.07.005. eCollection 2022 Oct.

Authors

Affiliations

¹ Urological Research Laboratory and Department of Urology, University of Bern, Inselspital, Bern, Switzerland.
² Department of Oncology, University of Bern, Inselspital, Bern, Switzerland.
³ Institute of Pathology, University of Bern, Bern, Switzerland.
⁴ Swiss Group for Clinical Cancer Research (SAKK) Coordinating Center, Bern, Switzerland.

Abstract

Background: Molecular detection of lymph node (LN) micrometastases by analyzing mRNA expression of epithelial markers in prostate cancer (PC) patients provides higher sensitivity than histopathological examination.

Objective: To investigate which type of marker to use and whether molecular detection of micrometastases in LNs was predictive of biochemical recurrence.

Design setting and participants: LN samples from PC patients undergoing radical prostatectomy with extended LN dissection between 2009 and 2011 were examined for the presence of micrometastases by both routine histopathology and molecular analyses.

Outcome measurements and statistical analysis: The mRNA expression of a panel of markers of prostate epithelial cells, prostate stem cell-like cells, epithelial-to-mesenchymal transition, and stromal activation, was performed by quantitative real-time polymerase chain reaction. The expression levels of these markers in LN metastases from three PC patients were compared with the expression levels in LN from five control patients without PC in order to identify the panel of markers best suited for the molecular detection of LN metastases. The predictive value of the molecular detection of micrometastases for biochemical recurrence was assessed after a follow-up of 10 yr.

Results and limitations: Prostate epithelial markers are better suited for the detection of occult LN metastases than molecular markers of stemness, epithelial-to-mesenchymal transition, or reactive stroma. An analysis of 1023 LNs from 60 PC patients for the expression of prostate epithelial cell markers has revealed different expression levels and patterns between patients and between LNs of the same patient. The positive predictive value of molecular detection of occult LN metastasis for biochemical recurrence is 66.7% and the negative predictive value is 62.5%. Limitations are sample size and the hypothesis-driven selection of markers.

Conclusions: Molecular detection of epithelial cell markers increases the number of positive LNs and predicts tumor recurrence already at surgery.

Patient summary: We show that a panel of epithelial prostate markers rather than single genes is preferred for the molecular detection of lymph node micrometastases not visible at histopathological examination.

Keywords: Extended lymphadenectomy; Isolated tumor cells; Lymph nodes; Metastasis; Micrometastasis; Molecular detection; Molecular markers; Prostate cancer; mRNA expression.