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Observational Study
. 2023 Aug 4;24(15):12436.
doi: 10.3390/ijms241512436.

Impact of Somatic DNA Repair Mutations on the Clinical Outcomes of Bone Metastases from Castration-Resistant Prostate Cancer

Maria Concetta Cursano  1 , Emilio Francesco Giunta  1 , Emanuela Scarpi  2 , Chiara Casadei  1 , Alessandra Virga  3 , Paola Ulivi  3 , Sara Bleve  1 , Nicole Brighi  1 , Giorgia Ravaglia  2 , Francesco Pantano  4 , Vincenza Conteduca  5 , Daniele Santini  6 , Ugo De Giorgi  1
Affiliations
Observational Study

Impact of Somatic DNA Repair Mutations on the Clinical Outcomes of Bone Metastases from Castration-Resistant Prostate Cancer

Maria Concetta Cursano et al. Int J Mol Sci. .

Abstract

Up to 80% of castration-resistant prostate cancer (CRPC) patients develop bone metastases during the natural history of disease and about 25% harbor mutations in DNA damage repair (DDR) genes. This retrospective observational study evaluated the prevalence of DDR alterations in CRPC patients and their effect on the clinical outcomes associated with bone metastases. The mutational status of CRPC patients was analyzed per FoundationOne® analysis in tissue biopsy or, when it was not possible, in liquid biopsy performed at the onset of metastatic CRPC (mCRPC). The impact of DDR gene mutations on bone-related efficacy endpoints was evaluated at the time of mCRPC diagnoses. In total, 121 mCRPC patients with bone metastases were included: 38 patients had mutations in at least one DDR gene, the remaining 83 ones had a non-mutated DDR status. DDR mutated status was associated with bone metastases volume (p = 0.006), but did not affect SRE (skeletal-related events) incidence and time to SRE onset. Liquid and tissue biopsies were both available for 61 patients with no statistically significant difference in terms of incidence and type of molecular DDR alterations. Mutated DDR status was associated with higher bone metastasic volume, although a not detrimental effect on the other bone-related efficacy endpoints was observed.

Keywords: DDR deficiency; DNA damage repair; SRE; bone metastases; liquid biopsy; mCRPC; prostate cancer; sheletal related events.

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Conflict of interest statement

U.D.G: Consultant: Janssen, AstellasPharma, Sanofi, Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Ipsen, Merck; Institutional funding: Roche, Sanofi, AstraZeneca. EFG: travel accommodation from Janssen-Cilag; M.C.C. travel accommodation from IPSEN; V.C. has served as a consultant/advisory board member for Janssen, Astellas, Merck, AstraZeneca, Amgen and Bayer and has received speaker honoraria or travel support from Astellas, Janssen, Ipsen, Bayer, Bristol and Sanofi; D.S. Onoraria per adv board con janssen MSD Merck Daiichi Sankyo Novartis Astellas roche SERVIER EISAI Gilead Incyte; F.P. advisory board per Lilly, Gilead, Novartis, AstraZeneca.

Figures

Figure 1
Figure 1
Distribution of molecular alterations found in solid and liquid biopsies.
Figure 2
Figure 2
Number of bone metastases in the two molecular groups (DDR mutated, group A versus DDR wild type, Group B), adopting the threshold of 10 lesions.
Figure 3
Figure 3
Time from bone metastases onset to death according to molecular status (DDR mutated, group A versus DDR wild type, Group B).
See this image and copyright information in PMC

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