By Mark T. Fleming, MD
Detecting, understanding and treating prostate cancer has evolved rapidly in recent years, offering patients new hope and increasingly requiring a multidisciplinary approach to care.
One of the most exciting advances in the field is targeted radioligand imaging and therapy. Both target prostate-specific membrane antigen (PSMA), a protein that is highly expressed on the surface of prostate cancer cells.
By injecting a PSMA-targeted radioactive diagnostic agent during PET scans, we can precisely pinpoint tumors to guide treatment. To date, the FDA has approved two such agents that locate PSMA-positive lesions more effectively than conventional CT and bone scans. Good candidates include men with still-elevated PSA levels despite chemotherapy, radiation and/or surgery.
On the treatment side, the intravenous medication lutetium-177—PSMA-617 is designed to deliver beta-particle radiation to metastatic cancer cells by attaching to PSMA receptors. That radiation then can damage or destroy tumors while sparing nearby healthy tissue.
The Phase 3 VISION clinical trial showed radioligand therapy added to standard care – chemotherapy and androgen receptor targeted therapy – prolonged imaging-based progression-free survival and overall survival as compared to standard care alone. The trial studied patients with metastatic castration-resistant cancer, often a fatal disease.
Additionally, researchers found the combination therapy improved patients’ quality of life and lessened the risk of worsening pain. Definitive clinical trials are now underway that may fuel a movement to use this treatment earlier during the prostate cancer journey.
Meanwhile, genomic testing has vastly improved our knowledge of different types of prostate cancers and how varied they can be. Put simply, we now understand that prostate cancer is a truly heterogenous disease.
Next-generational sequencing of germline and somatic mutations has become standard in higher-risk patients, including those with a family history of disease, and driven a rapid increase in targeted treatments such as PARP inhibitors and immunotherapy.
Many promising clinical trials are ongoing. One potential therapy targets the PTEN pathway, as mutations of this gene can trigger tumor development. Another is focused on EZH2, a gene essential to the production of an enzyme that again can be involved in cancer initiation and spread.
As prostate cancer management grows more complex, it is no longer sufficient for just one specialty – historically, urology – to be involved in a patient’s care. Instead, a multidisciplinary approach should (at minimum) draw in urologists, radiation oncologists and medical oncologists, ideally with subspecialty expertise.
Radiologists who can interpret PSMA scans and pathologists experienced in prostate cancer genomics will be increasingly essential as well. This team-based framework is best achieved with virtual tumor boards and coordinated navigation in a community setting.
Patients should feel very optimistic about their futures as we catch prostate cancer sooner with sensitive imaging equipment, gain more insight into disease genetics, and embrace a continuously expanding number of treatment options.
Dr. Fleming is a fellowship-trained medical oncologist with Virginia Oncology Associates, practicing in its Norfolk and Hampton offices. With special interest in Genitourinary cancers and Phase I novel drug development, he is a principal investigator on multiple clinical trials. virginiacancer.com
