~25% of patients
with de with de novo mHSPC1
Summary video
PTEN deficiency is the predominant biomarker of PI3K/AKT pathway activation
Alterations to the PTEN gene leading to a detectable deficiency of the PTEN protein is one of the primary causes of PI3K/AKT pathway activation in prostate cancer.3,4
PTEN deficiency leading to PI3K/AKT pathway activation may occur in:
40–60% of patients
with mCRPC2,5
PTEN deficiency is a valuable prognostic biomarker in mHSPC
Co-occurring alterations in PTEN and other tumor suppressor genes contribute to the overall aggressiveness of the tumor.
Alterations in the PTEN gene, which can lead to PTEN protein deficiency, often overlap with other genetic aberrations.6–8
- Up to 40% of metastatic prostate tumors have co-occurring alterations in key tumor suppressor genes: PTEN, TP53 and RB16
- Alteration to one or more of these genes in mHSPC tumors is associated with earlier disease progression and poor prognosis7,8
34.2%
In a study of 1,508 patients with mHSPC in the US, 516 patients (34.2%) had PTEN-altered tumors. Worse overall survival outcomes were observed in patients with PTEN-altered tumors compared to those without PTEN-altered tumors8
Deficiency of the PTEN protein is an independent predictor of poor outcomes
Compared with PTEN proficiency, PTEN deficiency is associated with poorer outcomes1,9–12:
Shorter
recurrence-free
survival
Shorter time
to development
of mCRPC
Shorter
overall survival
Patients with de novo mHSPC with PTEN deficiency have significantly shorter progression-free and overall survival compared with patients with PTEN proficiency.1
Shorter progression-free survival (PFS)
11.9 months
30.6 months
Months
Median PFS with PTEN deficiency (n=58)
Median PFS without PTEN deficiency (n=147)
Progression-free survival was defined as the time from commencing androgen deprivation therapy to the date of progression to mCRPC.
Shorter overall survival (OS)
43.8 months
80.2 months
Months
Median OS with PTEN deficiency (n=58)
Median OS without PTEN deficiency (n=147)
In mHSPC or mCRPC, when compared with PTEN proficiency, PTEN deficiency was associated with10:
- Shorter median overall survival (14 months versus 21 months; p=0.004)
- Shorter median duration of abiraterone treatment (24 weeks versus 28 weeks; p=0.009)
Routine testing for PTEN deficiency can1,9,13:
Identify more aggressive,
high-risk forms of mHSPC
Inform early treatment approaches that may potentially delay progression to mCRPC and prolong survival
Clinical case studies
Explore real-world patient case studies on the application of PTEN deficiency as a measure of prognosis, and how this can impact clinical decision-making and patient outcomes.
Somatic tumor testing to identify PTEN deficiency
A clinical case study by Dr Isla Garraway
View and download (PDF)
IHC and NGS to identify PTEN deficiency
A clinical case study by Dr Neal Shore
View and download (PDF)Ongoing research into biomarker-driven approaches may help to refine precision-medicine strategies for PTEN-deficient mHSPC
Advancing understanding of how PTEN deficiency contributes to disease progression via the PI3K/AKT pathway may inform future personalized therapies for patients with PTEN-deficient mHSPC.2
PTEN alterations have been associated with a worse prognosis in patients with advanced prostate cancer. The ability to accurately identify and interpret these alterations offers the potential to tailor treatments more effectively and improve patient outcomes.
Key publications
Explore key publications to learn more about PTEN and the impact of PTEN status on clinical outcomes in metastatic prostate cancer.
Explore key publications
knowledge check
AKT, protein kinase B; mCRPC, metastatic castration-resistant prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer; OS, overall survival; PFS, progression-free survival; PI3K, phosphoinositide 3-kinase; PTEN, phosphatase and tensin homolog; RB1, retinoblastoma 1; TP53, tumor protein p53.
1. Zhang JY, et al. Asian J Androl. 2022;24(1):50–55; 2. Turnham DJ, et al. Cells. 2020;9(11):2342; 3. Ikeda S, et al. Cancer Biol Ther. 2019;20(2):219–226; 4. Brown JS, Banerji U. Pharmacol Ther. 2017;172:101–115; 5. Crumbaker M, et al. Cancer. 2017;9(4):34; 6. Watson AP, et al. Am J Clin Exp Urol. 2020;8(4):106–115; 7. Gonzalez Velez M, et al. Prostate Cancer Prostatic Dis. 2022;25:476–483; 8. Rathkopf D, et al. Presented at ASCO Annual Meeting; May 30-June 3, 2025; Chicago, IL. Poster 5096; 9. Jamaspishvili T, et al. Nat Rev Urol. 2018;15(4):222–234; 10. Ferraldeschi R, et al. Eur Urol. 2015;67(4):795–802; 11. Lotan TL, et al. Eur Urol Focus. 2016;2(2):180–188; 12. Al-Toubat M, et al. Urol Oncol. 2023;41(11):455.e7–455.e15; 13. Ryan CJ, et al. J Urol. 2021;206(6):1420–1429.
