Genomic Testing

In a recent interview, Rohan Garje, MD, chief of genitourinary oncology at the Miami Cancer Institute, discussed the evolving paradigm with PARP inhibitors in prostate cancer.

“This is the first study in upper tract urothelial carcinoma to show that ctDNA may be used to refine clinical staging and prognosis in these patients prior to surgery,” says Heather L. Huelster, MD.

"In this study, we sought to evaluate the utility of a non-invasive biomarker—ctDNA—in predicting muscle-invasive and non–organ-confined staging of upper tract urothelial carcinoma," says Heather L. Huelster, MD.

The model may help identify patients with urothelial carcinoma who could benefit from PPARG inhibition through FX-909, a first-in-class small molecule inhibitor of PPARG.

“Our results provide molecular insights for potential therapeutic strategies to treat prostate cancer and other AR-involved diseases by targeting AR multivalent interactions,” said Zhijie “Jason” Liu, PhD.

"These tests, germline and tumor somatic testing, are extremely important and can no longer be ignored in the clinic when we see these patients," says Neeraj Agarwal, MD.

Alexandra Sokolova, MD, explains the importance of genetic testing for patients with high-risk localized and advanced prostate cancer, as well as for their high-risk family members.

The Invitae Common Hereditary Cancers Panel utilizes DNA taken from a blood sample to identify the presence of variants in 47 genes linked to an increased risk of developing certain cancers.

In patients with microhematuria, a positive result on the test was associated with a 5-fold increase in the risk of patients harboring bladder cancer compared with current metrics alone.

When compared with standard risk factors, only Decipher Prostate Genomic Classifier scores were independently associated with metastasis-free survival and distant metastasis.

This is the largest prostate cancer study that examined the exome, according to the researchers, who believe their findings can potentially inform the makeup of panels used for genetic testing in prostate cancer.

Data showed that the proportion of Black patients referred for genomic testing increased from 19% to 58% after the implementation of the precision medicine navigator.

The findings suggest that drug therapies targeting the NOTCH1 gene may serve as an alternative treatment option for patients with kidney cancer in whom surgery is not recommended.

Patients with mCRPC will be randomly assigned 2:1 to receive masofaniten/enzalutamide or enzalutamide alone.

“It’s exciting that now in 2023 we have 3 FDA-approved PARP inhibitors for the treatment of our prostate cancer patients,” says Joshi Alumkal, MD.

Joshi Alumkal, MD, discusses the phase 3 TALAPRO-2 trial, which supported the FDA approval of the combination of talazoparib and enzalutamide for patients with metastatic castration-resistant prostate cancer whose tumors harbor homologous recombination repair gene defects.

The approval of the olaparib/abiraterone regimen was based on an exploratory subgroup analysis of the phase 3 PROpel trial consisting of the 85 patients in the study with BRCA-positive metastatic castration-resistant prostate cancer.

Approximately half of prostate cancer patients with clinically actionable gene variants do not meet the NCCN guideline criteria for genetic testing, according to findings from the PROCLAIM trial.

The FoundationOne CDx test will identify patients who are eligible to receive niraparib plus abiraterone based on the genomic profile of their prostate tumor.

The approval of the niraparib/abiraterone dual-action tablet for BRCA-positive mCRPC is based on findings from the phase 3 MAGNITUDE study.

“We are now doing more testing on the RNA side,” says Brittany M. Szymaniak, PhD, CGC.

The study assessed US veterans receiving care at the Veterans Health Administration for all cancer types, including prostate cancer.

Patients classified as GC high risk had a 5-year disease progression of 40%, compared with 20% among GC low-risk patients.

This marks the first worldwide approval for the niraparib/abiraterone dual-action tablet.

The investigators identified several genetic factors, including ARID1A mutation, that correlated with survival outcomes in patients with advanced urothelial carcinoma treated with immune checkpoint blockade.

"In our sample, nearly 10% of patients [with prostate cancer] had a gene variant that made them eligible for effective new therapies, with faster results than traditional referral for genetic testing and counseling,” said Maria I. Carlo, MD.

Michael S. Leapman, MD, MHS, highlights a study of patient experiences with tissue-based genomic testing during active surveillance for prostate cancer.

Researchers identified 9 novel susceptibility loci for prostate cancer, 7 of which were substantially more prevalent in patients of African ancestry.

“Vanderbilt researchers are participating in numerous projects related to PRS and disease risk; studies such as this highlight the importance of evaluating whether novel clinical tools actually enhance care,” said Kerry Schaffer, MD.

There currently 2 PARP inhibitors—olaparib and rucaparib—approved as monotherapies for the treatment of patients with metastatic castration-resistant prostate cancer.