276P - Prognostic significance of p53 mutation in metastatic hormone-sensitive prostate cancer

Background

Metastatic hormone sensitive prostate cancer (mHSPC) is now in abundance of treatment options. In this heterogenous group, appropriate biomarkers to choose treatment decisions are unavailable. The present study aimed to assess the prognostic significance of p53 in metastatic prostate cancer patients.

Methods

Patients ≥18 yrs of age, newly diagnosed high volume (CHAARTED criteria) mHSPC, adenocarcinoma histology & gleason score ≥8 were considered for the study. Those with known/suspected cancer susceptibility were excluded. Aim of the study was to assess the p53 status in Indian mHSPC patients, time to castration resistance and overall survival stratified as per p53 status. Eligible patients received androgen deprivation therapy and docetaxel 75mg/m² q3weekly for 6 cycles. Immunohistochemistry for p53 was done on the prostate biopsy blocks and ≥20% nuclear immunoreactivity was considered as positive. Genomic DNA isolated from the tissue blocks was analysed for mutations in p53 exon 5 to 8 by PCR and confirmed by Sanger sequencing. At progression to CRPC, patients received therapy as per standard guidelines. The study started in 2019 after approval by the Institutional Ethics Committee.

Results

Out of 75 enrolled patients, 50 patients are eligible for present analysis. Among 50 high volume mHSPC patients, p53 was positive in 17 (34%) patients. In the overall population, progression to CRPC was seen in 26 (52%) patients at last follow up. Median follow up was 22 months. Time to CRPC in p53+ve vs. p53-ve patients was 16.6% and 37.6% (p-0.326). The 2yr OS was 51.9% vs 85.8% (p53+ve vs p53-ve respectively, p-0.041). Out of 11 samples tested, 6 (55%) mutations were found: p53 exon 8 (c.280AGA>AAA, c.287GAG>AAA, c. 279-280 GGGAGA ins GGGAAGA, c.280-281AGA>AAG) and exon 7 (c.249CGG>CGA, c.231-233 ACCACCATCCAC ins ACCACCAATCCACC). Remaining data on mutation status is being analysed.

Conclusions

This analysis shows the poor OS among p53+ve metastatic prostate cancer patients in Indian population. However, their progression after 1^st-line docetaxel chemotherapy was not statistically significant. Llimitation of the study is small sample size. Differential response of p53mutant patients to other approved treatment options in this disease needs to be explored.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Indian Co-operative Oncology Network (ICON).

Disclosure

All authors have declared no conflicts of interest.