Review: Era of Precision Medicine Dawning in Prostate Cancer

The use of prognostic and predictive molecular factors is bringing a new era of prostate cancer management into focus, according to a new report.

In a new review article published in the journal Cancers, investigators outlined the role of molecular biomarkers and the current state of precision prostate-cancer therapy.

Corresponding author Pasquale Rescigno, MD, of the Candiolo Cancer Institute in Italy, and colleagues, explained that even with new precision-medicine advances, the histopathological exam—including an evaluation of the cytological and architectural features of prostate cancer—remains “the cornerstone” of prostate cancer definition.

“Nevertheless, in the era of precision oncology, stratification of metastatic prostate cancer patients through molecular testing has gained a prominent role, even in the attempt of tackling resistance to approved drugs, which remains a key issue and is ultimately responsible for patients’ death,” they wrote.

Rescigno and colleagues began their review by outlining a number of predictive molecular factors that have been the subject of recent investigations, including androgen receptor alterations, loss of phosphatase and TENsin (PTEN) homolog, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment modifications. Those biomarkers have been linked to prognostic consequences, such as shorter overall survival and response to particular therapies, in various studies.

“Overall, the discovery of biologically distinct subtypes has revolutionized the historical assumption that prostate cancer is a homogenous disease with an indolent behavior,” they said. “There are indeed molecular characteristics that can significantly differentiate prostate cancers between patients and within the same patient overtime.”

For instance, the authors said patients with androgen receptor alterations tend to have poor survival and are less likely to respond to hormonal agents. Patients with PTEN loss have poor survival but may respond to AKT inhibitors. Patients with MMRd have shorter overall survival, but may respond to PD-1 inhibitors, the investigators noted.

Still, Rescigno and co-authors added that the studies identifying these biomarkers utilized different methodologies and platforms, and thus it is important that the findings are taken in the context of the particular methods and tissues used.

The investigators next turned to tissue specimens, asserting that they remain “crucial” to formulating a final diagnosis, even in an age when biomarker-specific screenings are available.

The authors said that while it is not yet clear which biological specimens are best to test, tissue samples give “the exquisite advantage to perform complementary analysis to genomic sequencing, such as immunohistochemical and TME (tumor microenvironment) studies.”

Plasma or blood derivatives have advantages, too, including ease of collection and the availability of serial specimen collection.

“Preservation of archival tissue, feasibility of fresh tissue biopsy, and adequate tumor fraction in plasma remain the big limitations of these tests,” they added.

For now, Rescigno and colleagues said, there is no unique test or tissue that can provide all of the necessary information to fully represent a patient’s disease biology. Absent that, they said both tumor and blood should be used to study predictive and prognostic factors in metastatic castration-resistant prostate cancers, and to investigate new mechanisms of resistance to approved treatments.

Reference:

Giunta EF, Annaratone L, Bollito E, et al. Molecular Characterization of Prostate Cancers in the Precision Medicine Era. Cancers (Basel). Published online September 24, 2021. doi:10.3390/cancers13194771