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PTEN Loss of Function Associated With Worse Survival in Metastatic CRPC

February 19, 2021


Shilpa Gupta, MD, Cleveland Clinic, Ohio, discusses a retrospective cohort study describing patient characteristics and survival outcomes according to phosphatase and tensin homolog (PTEN) loss of function status among patients with metastatic castration-resistant prostate cancer (CRPC) in real-world practice.

The results from this study were presented at the virtual ASCO Genitourinary Cancers Symposium.


Hello, I'm Dr. Shilpa Gupta. I'm a genitourinary oncologist at the Cleveland Clinic. I will be discussing our abstract that we presented at ASCO GU 2021. This was overall survival in patients with metastatic, castrate‑resistant prostate cancer who have PTEN tumor‑suppression gene loss of function. 

We know that around 50% of patients with metastatic CRPC have functional loss of PTEN tumor‑suppressor gene. Prior cohort studies in patients with metastatic CRPC treated with docetaxel or docetaxel followed by abiraterone demonstrated that PTEN loss of function by IHC correlated with increased risk of death compared to patients with intact PTEN.

Based on nationwide clinical practice data, there's limited information on the prognostic significance of PTEN loss of function identified via genomic testing. We wanted to examine patient characteristics and survival outcomes by PTEN loss‑of‑function status identified by genomic testing among patients with mCRPC in real‑world clinical practice.

We used a nationwide US‑based deidentified Flatiron Health, Foundation Medicine CGDB and obtained deidentified data from approximately 280 US cancer clinics. The data were derived from patient‑level EHR data and linked to the genomic data derived from the FMI CGP tests. 

The study outcomes were overall survival rates and mortality risk by PTEN loss‑of‑function status from the date of metastatic CRPC diagnosis until death or end of study follow‑up. 

We used an algorithm to select patients. Ultimately, we found that there were 284 patients without PTEN loss of function and 174 patients had PTEN loss of function out of the initial cohort of 974 patients, where we had information about PTEN loss‑of‑function status in about 513 patients.

38% of patients had a PTEN loss of function in our cohort. Majority of them were white with 9% African American patients. Importantly, patients in the no PTEN loss‑of‑function cohort, they were 11% African American patients compared to 5% with PTEN loss‑of‑function status.

Based on the Kaplan‑Meier estimates adjusted for left truncation, the median overall survival was shorter in the PTEN loss‑of‑function group. It was 14.3 months in this group compared to 18.3 months in the no PTEN loss‑of‑function group.

In the multivariate Cox model, the PTEN loss‑of‑function group had a 30% higher risk of death numerically compared with the PTEN not‑loss‑of‑function group. African American and Black race was associated with increased risk of death. Further research is needed to fully understand the interaction of race and PTEN status.

There are several limitations including confounding that may remain in the survival analysis even after controlling for the confounders in the Cox model. Some variables were either not available or not well‑captured in the data, like the site of metastases, performance status, etc.

Conclusions: among real‑world patients with metastatic CRPC who underwent CGP testing, PTEN loss of function determined by genomic profiling could be associated with poorer survival outcomes, potentially highlighting an unmet need among these patients.

Additional prospective studies with larger cohorts are needed to better evaluate survival outcomes in patients with PTEN loss of function. Importantly, therapeutic agents acting on the PI3K/Akt PTEN pathway are being tested in clinical trials and could potentially improve outcomes in patients with metastatic CRPC who have PTEN loss of function. Thank you.   

Gupta S, Abbass IM, Craggs C. Overall survival of patients with metastatic castrate-resistant prostate cancer (mCRPC) who have PTEN tumor suppressor gene loss of function. Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 58.

Dr Gupta reports no relevant financial relationships.

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