Genomic Testing

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

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.

The application is supported by findings from the phase 3 MAGNITUDE study.

The GPS test uses a 17-gene signature to predict disease aggressiveness and help guide treatment decisions for patients with localized prostate cancer.

IsoPSA is included in the National Comprehensive Cancer Network Prostate Cancer guidelines for early detection of the disease.

Here is some of the top content on genomic testing from the past year.

The study found pathogenic or likely pathogenic variants in DNA damage repair genes and HOXB13 to be more frequently observed in Black men with a family history of cancer.

UriFind uses a urine sample to assess whether a patient has bladder cancer, avoiding an invasive cystoscopy.

“At this time, there are at least 2 classes of therapeutic agents which are used for patients with certain germline or somatic genetic mutations,” says Emmanuel S. Antonarakis, MD.

HIF-2α inhibitors, such as belzutifan (Welireg), are a promising new class of agents emerging in the renal cell carcinoma treatment paradigm, explains Eric Jonasch, MD.

“Many urologists in large group practices are doing genetic testing, especially for their high-risk patients,” says Emmanuel S. Antonarakis, MD.

“Our study offers molecular and cellular insights into this aggressive subtype of prostate cancer, which we hope will ultimately impact patient care,” said the study’s lead author, Hong Yuen Wong, PhD.

“Prostate cancer is…a BRCA-linked cancer, so we can increase the messaging surrounding prostate cancer on social media platforms, we can increase the amount of awareness on the genetic link that exists with prostate cancer, so that patients are also more empowered to bring this up with their providers,” says Sameer Thakker, MD.

“The other aspect of this study that really fascinated us was how patients are getting information about cancer genetic testing,” says Sameer Thakker, MD.

All patients with prostate cancer, except for those with low-risk or very low-risk localized disease, should be tested for germline mutations, and somatic testing should be done in all patients with metastatic disease as there are therapeutic implications, according to Emmanuel S. Antonarakis, MD.

A higher score on PORTOS, an expression signature of 24 DNA damage repair and immune pathway genes, predicted improved response to dose-intensified salvage radiotherapy after radical prostatectomy in patients with biochemically recurrent prostate cancer.

"Clinicians now have access to tools that can assist them with turnaround times and report interpretation, thereby aligning with national guidelines on genetic testing,” said Neal Shore, MD.

Researchers hope to find synergistic effects with the combination of the ribosomal RNA synthesis inhibitor pidnarulex and the PARP inhibitor talazoparib.

Moffitt Cancer Center conducted the first prospective study to investigate genomic biomarkers associated with aggressive disease in African American men with prostate cancer

Research findings suggest that SLIT2 loss in circulating tumor cells promotes metastasis and enhances cancer progression, according to a Northwestern Medicine study published in Science Advances.

The talazoparib/enzalutamide combination was also shown to have benefits in key secondary end points, including prostate specific antigen (PSA) response, time to PSA progression, and overall response rate.

“Men with this type of metastatic prostate cancer want to get their genetically targeted therapy as early as possible, and this trial clearly shows the value of rucaparib as a treatment for these men,” said Alan H. Bryce, MD, principal investigator of the TRITON3 trial.

Cell-free DNA–based next-generation sequencing profiling resulted in low detection/concordance in clear cell renal cell carcinoma.

“There’s a tremendous amount of work going on right now with PARP inhibitors in the resistant stage, but now also we’re looking at them in the sensitive stage,” says Neal D. Shore, MD.

The presence of more than 2 tertiary lymphoid structures coupled with increased density of Ki-67 and PD-1 positivity was linked to an increased response rate and prolonged progression-free survival.

In a phase 2 trial, patients with metastatic urothelial carcinoma and DNA repair deficiency who had not progressed on chemotherapy were randomized to either rucaparib maintenance or placebo.