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SPOP-Mutant Prostate Cancer Subtype, High PSA, and Prognosis

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Key Points

  • The investigators discovered that the SPOP-mutant subtype was less likely to spread beyond the prostate, even with PSA levels of more than 20 ng/mL.
  • Overall, this subtype was associated with improved survival, despite a high PSA.

Conventional wisdom suggests that a high level of the protein prostate-specific antigen (PSA) in men with prostate cancer means a poor prognosis. However, this may not always be the case in men with a particular subtype of prostate cancer, according to a new study from Weill Cornell Medicine and NewYork-Presbyterian researchers.

PSA levels are often higher in men with prostate cancer and, typically, the higher the PSA, the worse their prognosis. However, researchers found that prostate cancer patients with a high PSA score and tumors with a mutation in the SPOP gene may have a less threatening form of disease, according to a study published by Liu et al in JCO Precision Oncology.

“These findings are counterintuitive,” said co-senior author Christopher Barbieri, MD, PhD, Assistant Professor of Urology at Weill Cornell Medicine. “In general, if your PSA is higher, the cancer is more dangerous. However, this study found that tumors associated with a high PSA and SPOP mutations were less dangerous.”

Study Findings

The investigators discovered that the SPOP-mutant subtype was less likely to spread beyond the prostate, even with PSA levels of more than 20 ng/mL (4 ng/mL is considered normal). Overall, this subtype—which affects about 20,000 men in the United States, or approximately 10% of those diagnosed with prostate cancer—was associated with improved survival, despite a high PSA.

Dr. Barbieri and his colleagues evaluated several cancer databases containing information on tumors from more than 8,000 men. The researchers developed a computer algorithm to classify which tumors had SPOP mutations.

Instead of looking at mutations in DNA, they evaluated RNA. There are two advantages to studying RNA rather than DNA. The first is the technology used to evaluate RNA is less expensive, said Dr. Barbieri. Second, RNA technology has been in use longer than DNA technology, providing the data scientists need to assess the effect of different prostate cancer subtypes on patient outcomes over the long term.

“It’s common for men to die of prostate cancer decades after diagnosis,” Dr. Barbieri said. Assessing RNA data allows researchers to determine the genetic makeup of tumors from groups of patients from 20 years ago.

The next step for Dr. Barbieri and his colleagues is to better understand how doctors can use PSA scores and the identification of prostate cancer subtypes to guide patient care. “We want to know whether specific types of treatments are better for some subtypes of prostate cancer vs others,” he said. 

While PSA scores can help doctors to create a treatment plan, the underlying cancer subtype also needs to be considered. “Higher PSA may not mean a worse prognosis in all prostate cancer subtypes equally,” Dr. Barbieri said. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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