Background
NEC is an aggressive form of prostate cancer with a poor prognosis[PMID: 23169519]. Previous research in a cohort of 30 patients with NEC showed significant enrichment for RB1 loss and TP53 mutation or deletion compared to AdenoK[PMID: 26855148]. Herein, we sought to compare the genomic landscape of NEC and AdenoK using a large real-world genomic dataset.
Methods
In this IRB-approved retrospective study, the de-identified Tempus Lens dataset identified patients with NEC and AdenoK across all stages with comprehensive genomic profiling. Baseline demographics were collected. Pathological variables were summarized using descriptive statistics and Chi-square test with a significance threshold of P<0.05. Genomic alterations with an incidence of ≥5% were analyzed. Homologous recombination repair (HRR) alterations in 14 pre-specified genes per the olaparib FDA label were compared.
Results
A total of 13,683 patients (AdenoK:13472; NEC:211) were analyzed. The median age of the NEC cohort was 65 [24–90+], with 55.9% identified as White, 37.9% were never smokers, and 32.7% were ex-smokers. In the AdenoK cohort, the median age was 66 [21–90+], with 45.4% identified as White, 36.62% never smoked, and 29.33% were ex-smokers. In the NEC cohort, the most common alterations were TP53(63.98%), RB1(53.08%), and PTEN(28.91%). The NEC cohort had a significantly higher prevalence of TP53(63.98 vs. 34.97%; P<0.001), RB1(53.08 vs. 6.09%; P<0.001), PTEN(28.91 vs. 18.1%; P<0.001), BRCA2(15.17 vs. 10.05%; P=0.01), TMPRSS2-ERG(25.12 vs. 19.29%; P=0.03), MYC(7.11 vs. 2.78%; P<0.001), CDKN1B(6.16 vs. 2.11%; P<0.001), and a lower frequency of SPOP(2.84 vs 9.22%; P=0.01), and ATM(6.64 vs. 12.33%; P=0.01). HRR alterations frequency was similar between NEC and AdenoK (38.83 vs. 38.66%, P=0.73).
Conclusions
This is the largest real-world study characterizing the genomic features of prostate NEC compared to AdenoK, consistent with prior studies suggesting a distinct genomic profile for NEC. These data enhance the understanding of the genetic drivers of this aggressive form of prostate cancer.