How can men over 70 with metastatic prostate cancer be identified and treated?

Questions and answers pertaining to the diagnosis and management of elderly men with metastasised cancer.

The US Preventive Services Task Force (USPSTF) establishes national guidelines for PSA-based prostate cancer screening. For men over 70, this independent panel of primary care and preventive specialists advises against prostate cancer screening.

Why? The growth of prostate cancer is often sluggish. Instead of dying from the condition, men in this age range are more likely to die with it. Furthermore, the USPSTF believes that the advantages of treating PSA-detected prostate cancer in older men are unlikely to exceed the risks of doing so.
However, this raises the prospect that men might not be examined for prostate cancer until the disease has progressed to a point where symptoms are present. We interviewed Dr. Marc B. Garnick, the editor-in-chief of the Harvard Medical School Guide to Prostate Diseases and the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Centre, for his thoughts on PSA screening and advanced prostate cancer treatment for older men.

What is the recommended screening frequency for prostate cancer in males over 70?

These tests are conducted outside of established protocols, usually after consulting with the patient’s doctor. We frequently discover advanced metastatic prostate cancer in older men who have had a PSA test. Some men only receive a PSA test when they experience severe signs of prostate cancer, such as fatigue, bone pain, or difficulty urinating, even though the illness may spread asymptomatically.
It is past time for the USPSTF to update its PSA screening standards, which were last released in 2018. We are all eagerly expecting the new standards, which are typically updated every six years, as the average life expectancy for males over 70 is rising.

Q. What kinds of further testing are performed following a PSA screening result that is positive?

Usually a needle biopsy of the prostate. Additionally, I advise a digital rectal exam (DRE) to check for prostate gland anomalies. According to reports, President Biden had a nodule on his DRE and was experiencing urinary problems at the time of his PSA test. His PSA score is unknown to us. More diagnostic information is now available through magnetic resonance imaging scans of the prostate, which can also be used as a guide to more accurately detect abnormalities in the prostate gland that can be sampled with a biopsy.

Q. How do we know if the cancer is likely to spread aggressively?

The more aggressive tumours have cells with irregular shapes and sizes that can invade into adjoining tissues. A time-honoured measure called the Gleason score grades the two most common cancer cell patterns that pathologists see on a biopsy sample.

That system has now undergone some labelling changes. To simplify matters, doctors developed a five-tier grading system that ranks tumours from Grade Group 1 — the least dangerous — to Grade Group 5, which is the most dangerous. These grade groups still correlate with Gleason scores. For example, Grade Group 1 is associated with a Gleason score of 3+3=6 for low-risk prostate cancer, while Grade Group 5 is associated with a Gleason score of 4+5=9 for high-risk illness.
Additionally, we can request genetic tests that provide more information or assess the mitotic rate, a measure of how quickly cancer cells divide. For example, we know that men who test positive for hereditary mutations in the BRCA1 and BRCA2 genes are more likely to have more aggressive illness. Because the same mutations increase the risk of other inherited malignancies, such as breast and ovarian cancer, BRCA test results also affect family members. 

How can one determine whether cancer is spreading?

In the past, patients would receive a bone scan in addition to an abdominal and pelvic computed tomography scan. These tests, which check for metastases in the bones and lymph nodes, are becoming less and less accurate. Prostate-specific membrane antigen (PSMA) is a protein that can be expressed at high levels on the surface of tumour cells, and doctors are increasingly scanning for it.
Prostate tumours that are still too small to be seen with other imaging tests can be found considerably more easily with a PSMA scan. Depending on the extent, we categorise men with either high-volume or low-volume illness if the scans reveal evidence of metastatic dissemination. Oligometastatic prostate cancer is defined as affecting men with no more than three to five metastases.

What options are there for treating prostate cancer that has spread?

Usually, we don’t start with just one medicine. Doublet therapy, which consists of two medications that each deprive tumours of testosterone — a hormone required for prostate cancer growth — is commonly used to men with low-volume metastatic prostate cancer.
Leuprolide (Lupron), one of the medications, prevents the production of testosterone. The remaining treatments belong to a class of pharmaceuticals that block the binding of testosterone to its cell receptor. These medications are known as androgen receptor pathway inhibitors, or ARPIs for short. These consist of apalutamide (Erleada), daralutamide (Nubeqa), enzalutamide (Xtandi), or abiraterone (Zytiga), a medication with a somewhat different mechanism.

Chemotherapy may be added if doublet therapy fails to control the malignancy. Triplet therapy is what this is known as (Lupron + ARPI + chemotherapy). Depending on how far the cancer has gone, we might also advise triplet therapy right away.
Other treatments are also available to some guys. For example, Lutetium-177, an injectable medication, can be used to treat males with PSMA-positive illness, which means that their cells express the protein in significant numbers. This kind of treatment, called a radioligand, locates cells that express PSMA and uses microscopic radioactive particles to destroy them.

Metastasis-directed treatment (MTD) is available for certain men. In these situations, we use externally delivered, intensely focused radiation beams to treat metastatic deposits. Patients with oligometastatic prostate cancer are typically the only ones eligible for MTD.

What occurs if a patient tests positive for prostate cancer on a genetic test?

This creates opportunities for what is known as 'targeted therapy', a phrase used to refer to medicines that target particular cell alterations that lead to tumour growth. For example, patients with BRCA1 or BRCA2 mutations may begin doublet therapy in addition to a PARP inhibitor, a targeted treatment. Two PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza), are authorised for the treatment of prostate cancer in men with BRCA. Pembrolizumab (Keytruda) is a targeted medication for men with microsatellite instability, a distinct gene mutation.

What changes are we seeing in the prognosis for metastatic prostate cancer?

It’s getting much better! The prognosis for metastatic prostate cancer used to be extremely bad. Men with the condition now frequently live for ten years or more. We’re even beginning to treat prostate cancer directly, which we didn’t do previously because the cancer had already spread outside of the prostate gland. In patients with metastatic disease, more recent research has demonstrated advantages to administering radiation directly to the prostate gland. Previously, we would not have thought of including these treatments, but we are now doing so more frequently.

Q. Any last thoughts?

Men should get a heart examination before beginning hormone medication, in my opinion. Cardiovascular risk factors should be addressed both prior to and throughout therapy because hormonal treatments have the potential to worsen them.