Genomic determinants of patterns of failure in metachronous oligometastatic castration-sensitive prostate cancer.

Media type: E-Article

Title: Genomic determinants of patterns of failure in metachronous oligometastatic castration-sensitive prostate cancer

Contributor: Sutera, Philip; Van der Eecken, Kim; Shetty, Amol; Song, Yang; Hodges, Theresa; Verbeke, Sofie; Van Dorpe, Jo; Fonteyne, Valerie; De Laere, Bram; Mishra, Mark V.; Rana, Zaker Hamid; Molitoris, Jason K.; Ferris, Matthew J.; Roberts, Nicholas J; Song, Daniel Y.; DeWeese, Theodore L.; Pienta, Kenneth J.; Deek, Matthew; Ost, Piet; Tran, Phuoc T.

imprint: American Society of Clinical Oncology (ASCO), 2023

Language: English

DOI: 10.1200/jco.2023.41.6_suppl.238

ISSN: 0732-183X; 1527-7755

Keywords: Cancer Research ; Oncology

Origination:

Footnote:

Description: 238 Background: Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state along the progression of metastatic disease in which patients experience improved outcomes compared to those with higher disease burden. Despite the generally more indolent nature, much heterogeneity still exists with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Here we correlate tumor genomics with modes of progression (MOP) and patterns of failure (POF) following treatment for omCSPC. Methods: We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC, who underwent tumor next generation sequencing (NGS) with at least 1 year of follow-up. Descriptive POF and MOP were reported with respect to presence of genomic alterations in pathways of interest. Genomic pathways of interest included TP53, SPOP, WNT ( APC, CTNNB1, RNF43), DNA double strand break repair, cell cycle genes ( Rb1, CCND1–3, CDKN1B, and CDKN2A), and PI3K/AKT/mTOR. MOP were defined as oligoprogression (1-3 lesions), polyprogression (≥4 lesions), or long-term control (LTC, no radiographic progression at last follow-up). POF included location of lesions at first failure. Overall survival (OS) was calculated by the Kaplan-Meier method. Genomic associations with patterns/modes of failure were compared with chi-square test. Results: 221 patients were included for analysis with the majority having either 1 (47.5%) or 2 (27.3%) metastatic lesions at oligometastasis. 5-yr OS was associated with MOP 92% vs 89% vs 69% (p<0.01) for LTC, oligo- and polyprogression respectively. TP53 mutations were associated with significantly lower rates of LTC (24.4% vs 46%, p<0.01) and cell cycle mutations associated with high rates of polyprogression (36.7% vs 15.7%, p<0.01). With respect to POF, bone failure was significantly more common within tumors harboring mutations in TP53 (41.2% vs 23.1%, p=0.01) and less common with SPOP mutations (4.2% vs 27.8%, p=0.02). Finally, visceral failures were more common in tumors harboring either WNT pathway (20% vs 5.1%, p<0.01) or SPOP (17.4% vs 5.2%, p=0.04) mutations. Notably, SPOP and WNT pathway mutations cluster together (p<0.01). Conclusions: Tumor genomics provides novel insight into patterns of failure and modes of progression following treatment for metachronous omCSPC. Patients with TP53 and cell cycle mutations have a higher likelihood of progression and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism.

Access State: Open Access

Search in field:

Recently searched for: