(UroToday.com) The 2024 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Marta Garcia De Herreros discussing tumor suppressor gene signature predicting early progression in mHSPC patients. Alterations on the tumor suppressor genes RB1, PTEN and TP53 are associated with treatment resistance, decreased survival and aggressive variants of prostate cancer. In previous work, the investigators developed and validated a signature of low expression of tumor suppressor genes that was associated with poor outcomes in mHSPC patients treated with ADT +/- docetaxel.1 At ESMO 2024, Dr. De Herreros and colleagues assessed their tumor suppressor genes signature in mHSPC patients treated with androgen receptor signaling inhibitors and explored clinical characteristics at progression.
This is a multicenter retrospective biomarker study in mHSPC patients, treated with ADT + androgen receptor signaling inhibitors. Tumor suppressor gene expression was assessed by nCounter platform in HSPC tumor samples. Tumor suppressor geneslow was considered when ≥2 out of 3 tumor suppressor genes presented low expression of a previously established cut-off, and tumor suppressor geneswt in the remaining cases. Tumor suppressor gene signature was correlated with CRPC-free survival (primary endpoint) by Kaplan Meier and multivariate Cox analysis. Aggressive variants of prostate cancer were considered if patients met ≥1 of the previously reported criteria at CRPC progression.2
There were 137 patients included in this study with a median age of 71.8 years (range 50.1-92.8). There were 77.4% of patients that presented de novo stage IV, 16.1% with visceral metastasis, and 53.3% high volume disease:
With a median follow-up of 30.7 months (2.7 - 91), 32% of patients died and 32.6% developed CRPC. Tumor suppressor geneslow (16.8 %) was independently associated with shorter CRPC-free survival (31.2 months vs NR, p = 0.042):
There was no difference in overall survival between tumor suppressor geneslow (median 56.4 months) compared to tumor suppressor geneswt (median 64.9 months; p = 0.707):
Among the 48 patients who developed CRPC, 42 had available data at the time of CRPC progression. There were 13 patients (30.9%) presenting with at least 1 aggressive variant of prostate cancer criteria. Overall, 66.7% of patients with tumor suppressor geneslow tumors presented with aggressive variants of prostate cancer versus 18.7% of the tumor suppressor geneswt (Fisher p = 0.01):
Five patients harbored PTENlow + RB1low tumors and all of them developed aggressive variants of prostate cancer criteria at progression. Metastatic tumor biopsy at progression was available for 5 patients, of which all showed neuroendocrine differentiation.
Dr. De Herreros concluded her presentation by discussing tumor suppressor gene signatures predicting early progression in mHSPC patients with the following take-home points:
- Tumor suppressor geneslow expression is associated with early CRPC progression in mHSPC patients treated with androgen receptor signaling inhibitors and could help to predict de development of aggressive variants of prostate cancer
- This supports the development of new therapeutic strategies in these patients
Presented by: Marta Garcia De Herreros, Hospital Clinic Barcelona, Barcelona, Spain
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Meeting, Barcelona, Spain, Fri, Sept 13 – Tues, Sept 17, 2024.
Related content: Tumor Suppressor Gene Signature Predicts Early Progression in mHSPC - Marta Garcia de Herreros
References:
- Jimenez N, de Herreros MG, Reig O, et al. Development and Independent Validation of a Prognostic Gene Expression Signature based on RB1, PTEN, and TP53 in Metastatic Hormone-Sensitive Prostate Cancer Patients. Eur Urol Oncol. 2024 Aug;7(4):954-964.
- Aparicio AM, Harzstark AL, Corn PG, et al. Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clin Cancer Res. 2013 Jul 1;19(13):3621-3630.