Primary Tumor Resection Decelerates Disease Progression in an Orthotopic Mouse Model of Metastatic Prostate Cancer

Johannes Linxweiler,Kerstin Junker,Matthias Saar,Philip Zeuschner,Michael D Menger,Turkan Hajili,Michael Stöckle

doi:10.3390/cancers14030737

Johannes Linxweiler, Kerstin Junker + Show 5 more

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https://doi.org/10.3390/cancers14030737

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Journal: Cancers	Publication Date: Jan 31, 2022
Citations: 13	License type: CC BY 4.0

Affiliation: Saarland University

Abstract

Simple SummaryIn this preclinical in-vivo study, we used an orthotopic prostate cancer mouse model to analyze the effects of primary tumor resection on further disease progression and survival in metastatic prostate cancer. Sixty-four mice with metastatic prostate cancer, induced by intraprostatic injection of three-dimensional prostate cancer spheroids, were randomized into two groups: one group received resection of their primary tumor while the other group received a sham operation. After this, the mice were followed-up for 10 weeks. In comparison with the sham operation group, mice with primary tumor resection showed significantly slower PSA progression, less lung metastases, and significantly longer survival. These results are a hint towards a beneficial oncological effect of primary tumor resection in metastatic prostate cancer. Furthermore, the established versatile in-vivo model can be used to study the molecular mechanisms of primary tumor/metastasis interaction in prostate cancer.Radical prostatectomy in oligometastatic prostate cancer is a matter of intense debate. Besides avoiding local complications, it is hypothesized that primary tumor resection may result in better oncological outcomes. The aim of our study was to analyze the effect of primary tumor resection on disease progression in an orthotopic prostate cancer mouse model. First, the optimal time point for primary tumor resection, when metastases have already occurred, but the primary tumor is still resectable, was determined as 8 weeks after inoculation of 5 × 105 LuCaP136 cells. In a second in vivo experiment, 64 mice with metastatic prostate cancer were randomized into two groups, primary tumor resection or sham operation, and disease progression was followed up for 10 weeks. The technique of orthotopic primary tumor resection was successfully established. Compared with the sham operation group, mice with primary tumor resection showed a significantly longer survival (p < 0.001), a significantly slower PSA increase (p < 0.01), and a lower number of lung metastases (p = 0.073). In conclusion, primary tumor resection resulted in slower disease progression and longer survival in an orthotopic mouse model of metastatic prostate cancer. In future studies, this model will be used to unravel the molecular mechanisms of primary tumor/metastasis interaction in prostate cancer.

Highlights

The possible beneficial effects of treating prostate cancer (PCa) via radical prostatectomy (RP) in patients suffering from metastatic PCa are a matter of controversial debate in recent years [1,2]
Several retrospective studies have shown that disease progression can be influenced by RP [9,10,11], and primary tumor treatment in oligometastatic PCa proved beneficial in the STAMPEDE trial [12]
Since novel imaging modalities based on prostate-specific membrane antigen (PSMA) are entering clinical routine, it is becoming evident that most of the highrisk localized PCa patients treated by RP or radiotherapy plus androgen deprivation therapy (ADT) do not, have localized but rather oligometastatic PCa [18,19]

Summary

Introduction

The possible beneficial effects of treating prostate cancer (PCa) via radical prostatectomy (RP) in patients suffering from metastatic PCa are a matter of controversial debate in recent years [1,2]. While cytoreductive primary tumor resection is well established in other cancers [3,4,5], this concept has only recently been included in the scientific debate over PCa. In addition to avoiding local complications, another rationale for RP in patients with metastasized PCa is to slow down disease progression by inhibiting the interaction between the primary tumor and metastases and removing potentially lethal tumor cell clones [6,7,8]. The number of patients suffering from oligometastatic PCa is probably much higher than previously thought, and a better understanding of the biology of this disease stage and a selection of optimal treatment approaches are necessary

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