In 2012, marines with Charlie Company, 1st Battalion, 8th Marine Regiment, patrol through a poppy field while searching for enemy combatants. Environmental exposures are considered one reason why veterans have higher rates of prostate cancer. Photo by Cpl. Ed Galo
DURHAM, N.C. — The U.S. government and the VA increasingly recognize the increased risk of prostate cancer faced by veterans and its relationship to service in areas of conflict. As a result, the VA continues to expand its services to veterans with the cancer and ensure access to the most current and effective diagnostic techniques and therapies, including novel uses of radioligands.
In 2022, the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act (PACT) Act recognized prostate cancer as a presumptive condition for veterans deployed after 9/11 and for those who served in the Gulf War. The act streamlines health benefits and compensation for veterans diagnosed with prostate cancer and acknowledges the increased risk of the malignancy faced by many warfighters.
Prostate cancer is also a presumptive condition for older veterans exposed to Agent Orange or other herbicides during the Vietnam era and in the Korean demilitarized zone. Studies demonstrated a 52% increase in the risk of prostate cancer for veterans exposed to Agent Orange compared to those who were not; their risk of aggressive prostate cancer also was doubled.1
While prostate cancer is the most common type of non-skin cancer in all men, veterans have nearly twice the risk of men who never served.2 Nearly one in five veterans will be diagnosed with the cancer, which accounts for 30% of all new cancer diagnoses in the VA, or about 15,000 diagnoses each year.
Approximately 489,000 veterans receiving care through the VA have a prostate cancer diagnosis. Of those, 16,000 have metastatic cancer.
Metastatic Castration-Resistant Prostate Cancer
Most men with prostate cancer who receive definitive local therapy never experience a recurrence, but 20% to 40% will eventually relapse. The first-line treatment for these men is hormone therapy that induces chemical castration, but many of them will eventually become resistant to this treatment and progress to metastatic castration-resistant prostate cancer (mCRPC).
The VA’s Precision Oncology Program and partnership with the Prostate Cancer Foundation have dramatically increased the number of veterans with mCRPC undergoing genetic testing to identify suitable targeted therapies, either commercially available or in clinical trials. Such testing is essential to maximize effectiveness and minimize adverse effects, given the tremendous genetic heterogeneity in prostate cancer. Drugs can specifically target microsatellite instability-high or mismatch repair-deficient cancers, as well as BRCA2 variants or other mutations in DNA repair genes.
Many men with mCRPC do not have targetable mutations, however, and some of those who do, may progress on to targeted therapies. A new option that is not restricted to specific mutations uses radioisotopes with minimal systemic effects or damage to surrounding tissues.
Radioligands use radiation to kill cancer cells, but its highly targeted action reduces the adverse effects seen with external radiation therapy. Conventional radiation therapy runs the risk of damage to nearby tissues, causing bowel, urinary and sexual dysfunction and, as a large VA study found, a “small, but significant” increased risk of secondary cancers, including leukemia, lymphoma, bladder or rectal cancer.3
In contrast, radioligands, compounds that combine a radioactive isotope and a biological tracer or ligand, operate inside the body where they seek out specific cancer molecules. For mCRPC, they target prostate-specific membrane antigen (PSMA), which is highly expressed on the surface of prostate cancer cells. For soft tissue mCRPC tumors, two radioactive molecules, lutetium-177 PSMA (Lu177-PSMA) and gallium-68 (Ga-68) PSMA are used together. Gallium-68 finds and “lights up” prostate cancer cells on a PET scan, regardless of where they are in the body, and the Lu177-PSMA binds to the same locations, but emits a more powerful form of radiation. The cancer cells absorb the radiation and die.
Recent studies indicate that PSMA-targeted radioligand therapy provides an effective option for patients with mCRPC who have few or no other alternatives, as discussed in the accompanying article on page xx.
VA Partnerships
The VA continues its commitment to bringing the best available care to veterans with prostate cancer, with detailed assessment of the burden of cancer for each patient.
New tools ensure that the cancer treatment chosen is appropriate for the extent of the disease. In early-stage prostate cancer, multi-parametric magnetic resonance imaging helps guide a biopsy to facilitate evaluation of the cancer. In advanced or potentially metastatic cases, PSMA PET/CT scans, such as those used therapeutically with Lu177-PSMA, enable visualization of other parts of the body where prostate cancer often metastasizes to determine the most appropriate treatment.
Researchers led by Thomas Dresser, MD, chief of nuclear medicine at the Harry S. Truman Memorial Veterans’ Hospital in Columbia, Mo., and Timothy Hoffman, PhD, professor of medicine at the University of Missouri-Columbia and a radiopharmaceutical chemist at the VA, pioneered use of Ga-68 in the VA as part of the phase III trial that led to the drug’s FDA approval.
“The PSMA PET scan helps us be able to assess different sites in the body that might have cancer, so that you’re not going to be treating patients [with surgery] who might already have metastatic disease, for example,” Michael Kelley, MD, executive director of the VA’s National Oncology Program, told U.S. Medicine.
“When a normal cell in the prostate gland becomes cancerous, the membrane of the cell begins to make too many copies of PSMA,” said Dresser. “The key to diagnostic precision is the use of this injectable radiopharmaceutical peptide designed for a specific cancer and used in conjunction with PET imaging.”
- Ansbaugh N, Shannon J, Mori M, Farris PE, Garzotto M. Agent Orange as a risk factor for high-grade prostate cancer. Cancer. 2013 Jul 1;119(13):2399-404. doi: 10.1002/cncr.27941. Epub 2013 May 13. PMID: 23670242; PMCID: PMC4090241.
- Zhu K, Devesa SS, Wu H, Zahm SH, Jatoi I, Anderson WF, Peoples GE, Maxwell LG, Granger E, Potter JF, McGlynn KA. Cancer incidence in the U.S. military population: comparison with rates from the SEER program. Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1740-5. doi: 10.1158/1055-9965.EPI-09-0041. PMID: 19505907; PMCID: PMC2780333.
- Bagshaw HP, Arnow KD, Trickey AW, Leppert JT, Wren SM, Morris AM. Assessment of Second Primary Cancer Risk Among Men Receiving Primary Radiotherapy vs Surgery for the Treatment of Prostate Cancer. JAMA Netw Open. 2022;5(7):e2223025. doi:10.1001/jamanetworkopen.2022.23025