Prostate carcinoma is the most common type of cancer among men in the United States, accounting for more than 299,000 estimated new cases and approximately 35,000 new deaths in 2024.1 A new ASCO guideline based on findings from a systematic review indicates that in metastatic cases of prostate cancer, both germline and somatic testing should be done, with panel testing used to detect genetic variants.2
“Prostate cancer is a disease where there are actionable mutations that can be detected; however, the testing for those mutations is not commonly done, especially in the community setting,” said Expert Panel Co-Chair Evan Y. Yu, MD, of Fred Hutchinson Cancer Center and the University of Washington.
Evan Y. Yu, MD
With other types of cancer, such as breast or lung tumors, the first thing practitioners mention to the patient is the presence of associated gene mutations such as those involving BRCA, HER2, or EGFR, which can affect the treatment plan, Dr. Yu pointed out. But with metastatic prostate cancer, this is not occurring. “There are clearly a good number of patients with prostate cancer whose cancers are being driven by mutations in certain DNA-repair genes like BRCA, and there’s still a lack of testing being done,” he said.
Unlike other types of cancer, where tumor genetics play a pivotal role in treatment, prostate tumors have not traditionally at the start of diagnosis been handled by medical oncologists, he continued. Dr. Yu noted that medical oncologists will often gear their treatment approach to precision medicine, taking the genetic makeup of the tumor into account. Instead, it has been urologists, often not as focused on genetics, who usually initiate treatment, with referrals coming to oncologists later in the disease course. This makes it important to expand education on the need for testing for gene mutations in prostate cancer when planning treatment beyond patients and oncologists to include urologists, he emphasized.
Inclusion Criteria
To determine the most essential recommendations for metastatic prostate cancer, a multidisciplinary expert panel conducted a systematic review of the evidence. “We looked for inclusion criteria that included patients with metastatic prostate cancer; studies that included germline and somatic genomic testing; and studies that looked at detection rates, incidence rates, prognostic information, and treatment information,” Dr. Yu said.
From the initial 1,713 PubMed papers screened, 14 studies were selected and used as the evidence basis for guideline recommendations. The studies included eight systematic reviews and six prospective clinical trials published between 2020 and 2024.3-16
Key Findings
The panel offered recommendations for those patients with metastatic prostate cancer with a 6-month or greater life expectancy and who were candidates for systemic treatment.
Next-Generation Sequencing: One pivotal recommendation involved germline testing with next-generation sequencing technology. “We felt that all patients with metastatic prostate cancer should receive germline testing, because the data show about 12% have some sort of inherited mutation,” Dr. Yu said. “That has significant implications not just for the patients’ potential treatment but also for their families in terms of counseling and downstream cascade testing.” Many mutations that lead to prostate cancer can also cause breast, endometrial, pancreatic, and ovarian cancers, he continued.
Investigators also strongly recommended somatic testing with next-generation sequencing technology for anyone with metastatic prostate cancer being considered for a biomarker-directed systemic treatment, such as a PARP inhibitor. Although other evidence suggests that this testing could be done for those patients being considered for checkpoint inhibitor therapy, this was not from level-1 randomized controlled trials, and investigators were unable to make a strong recommendation for those with metastatic prostate cancer, Dr. Yu said. It is something practitioners should be aware of in metastatic prostate cancer cases, he added, but there are no current recommendations to perform this testing.
Sequential Somatic Testing: For sequential somatic testing, the panel recommends this be done when there is a meaningful change in the patient’s status or treatment plan. This is particularly true in cases in which prior tests were negative or uninformative, there may not have been enough tumor content, or the quality of archival tissue is in question to get a positive result, Dr. Yu said. If a patient is clinically progressing despite previously testing negative and also seeking other treatment options, that might be a situation to retest, he continued.
The panel also considered the strengths and weaknesses of primary tumor archival tissue vs fresh metastatic biopsy or circulating tumor DNA testing for somatic testing. “We said that initially archival tissue samples are preferred, but [circulating tumor] DNA is preferred when there’s no accessible metastatic site to biopsy or for sequential testing,” Dr. Yu said. A metastatic biopsy is strongly recommended in cases of minimal disease burden, he added.
Continued Evolution
When implementing the new guideline, practitioners should be aware that education on the hereditary nature of the disease and the importance of genetic testing in guiding treatment is pivotal and must be geared not only patients and oncologists but also urologists, since prostate cancer treatment is a multidisciplinary specialty, Dr. Yu noted. Fortunately, this is beginning to shift, with those outside of oncology beginning to become more aware of the role of genetic testing, he went on. “I think that it’s changing and improving but needs to continue evolving,” Dr. Yu said. “Our education needs to span beyond the patients and beyond medical oncologists.”
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Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 22, 2025. All rights reserved.
