# Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer

Source: https://onco.cc/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/  
OnCo record `paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sequencing 424 men at the point their cancer had spread but before hormone treatment failed showed which genetic changes make castration resistance come sooner, and which make it come later.

## Summary

Clinical-grade targeted tumour sequencing was performed in men with metastatic castration-sensitive prostate cancer at a tertiary referral centre, quantifying copy-number alterations and alterations in predefined oncogenic signalling pathways. Among 424 men, 213 had high-volume disease and 211 low-volume disease, 275 had de novo metastatic disease and 149 metastatic recurrence of earlier non-metastatic disease. Rates of castration resistance and of death were higher in high-volume disease, and high-volume tumours carried more copy-number alterations, with the NOTCH, cell-cycle and epigenetic modifier pathways ranking highest. De novo metastatic disease differed from metastatic recurrence in the prevalence of CDK12 alterations but had similar prognosis. Rates of castration resistance differed 1.5-fold to 5-fold according to alterations in AR, SPOP (in the inverse direction) and TP53 and to the cell-cycle, WNT (inverse) and MYC pathways, adjusting for disease volume; overall survival differed 2-fold to 4-fold by AR, SPOP (inverse), WNT (inverse) and cell-cycle alterations. PI3K pathway alterations carried no independent prognostic weight.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Clinical Cancer Research
- Year: 2020
- DOI: 10.1158/1078-0432.CCR-20-0168
- Authors: Stopsack KH, Nandakumar S, Wibmer AG, et al.
- Findings: AR and TP53 alterations and cell-cycle and MYC pathway alterations associated with faster castration resistance.; SPOP and WNT alterations associated with slower castration resistance and longer survival.; CDK12 alterations differed between de novo metastatic disease and metastatic recurrence.; PI3K pathway alterations carried no independent prognostic weight after adjustment.
- What it means: It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.
- Caveats: Eighty-eight per cent of the men were White, at a single tertiary centre.; Targeted panel sequencing, so structural and non-coding events are invisible.; Prognostic associations, not a basis for withholding or intensifying treatment.

## Sources

- Stopsack et al., Clin Cancer Res 2020: oncogenic alterations, phenotypes and outcomes in 424 men with metastatic castration-sensitive prostate cancer: https://doi.org/10.1158/1078-0432.CCR-20-0168
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32220891/
- cBioPortal study prad_mcspc_mskcc_2020 (MSK, Clin Cancer Res 2020; 424 metastatic castration-sensitive prostate cancers): https://www.cbioportal.org/study/summary?id=prad_mcspc_mskcc_2020

## Connected records

- cancers: [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [APC](https://onco.cc/targets/apc/), [CDK12](https://onco.cc/targets/cdk12/), [SPOP](https://onco.cc/targets/spop/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [MYC](https://onco.cc/pathways/myc/), [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Driver mutation](https://onco.cc/terms/driver-mutation/), [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://onco.cc/terms/mcrpc-mhspc/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)
- biomarkers: [SPOP mutation](https://onco.cc/biomarkers/spop-mutation/)

---
JSON: https://onco.cc/api/v1/entities/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020.json