PSA Screening and Advanced Prostate Cancer Treatment in Men Over 70

National guidelines on prostate cancer screening with the PSA test are set by the US Preventive Services Task Force (USPSTF). This independent panel recommends against screening men older than 70 because prostate cancer tends to be slow-growing and these men are more likely to die with the disease rather than from it. The USPSTF concluded that survival benefits from treating PSA-detected prostate cancer in older men are unlikely to outweigh the harms of treatment. Nonetheless, many men only receive a PSA test after disease has progressed to symptomatic stages.

For further insight, we spoke with Dr. Marc B. Garnick, Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center.

How often should men over the age of 70 be screened for prostate cancer?

PSA testing in this age group is performed outside of USPSTF guidelines and generally follows a discussion with the patient’s physician. In practice:

  • Advanced metastatic prostate cancer is often flagged by a PSA test.
  • Some men only undergo PSA testing after developing symptoms such as trouble urinating, fatigue, or bone pain.
  • The USPSTF’s PSA screening guidelines were last published in 2018 and are due for update, generally every six years, especially as life expectancy for men over 70 increases.

What sort of other tests follow after a positive result with PSA screening?

After a positive PSA result, further evaluation typically includes:

  • Prostate needle biopsy to obtain tissue samples.
  • Digital rectal exam (DRE) to feel for prostate abnormalities.
  • Magnetic resonance imaging (MRI) scans of the prostate, which provide detailed diagnostic information and guide precise biopsy targeting.

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

Aggressive tumors exhibit irregular cell shapes and sizes that invade adjacent tissues. Assessment tools include:

  • Gleason score and Grade Groups: The traditional Gleason score grades the two most common cell patterns. A newer five-tier Grade Group system ranks tumors from Grade Group 1 (least dangerous) to Grade Group 5 (most dangerous). For example, Gleason 3+3=6 corresponds to Grade Group 1, while Gleason 4+5=9 corresponds to Grade Group 5.
  • Mitotic rate: Measures how fast cancer cells are dividing.
  • Genetic tests: Identify inherited mutations such as BRCA1 and BRCA2, which are associated with more aggressive disease and have implications for family members.

How do you know if the cancer is metastasizing?

Traditional imaging included CT scans of the abdomen and pelvis plus bone scans to detect spread to lymph nodes and bones. Modern practice favors:

  • PSMA scans: Detect prostate-specific membrane antigen expressed on tumor cells, identifying metastases too small for other imaging methods.
  • Disease volume classification: High- or low-volume disease based on extent of spread. Oligometastatic prostate cancer is defined as no more than three to five metastases.

What treatment options are available for metastatic prostate cancer?

Treatment typically begins with combination therapies rather than single agents. Options include:

  • Doublet therapy: For low-volume metastatic disease, combines two drugs that block testosterone: leuprolide (Lupron) plus an androgen receptor pathway inhibitor (ARPI) such as enzalutamide (Xtandi), darolutamide (Nubeqa), apalutamide (Erleada), or abiraterone (Zytiga).
  • Triplet therapy: Adds chemotherapy to doublet therapy if the cancer progresses, or is used immediately in extensive disease.
  • Radioligand therapy: Lutetium-177 targets PSMA-positive cells with radioactive particles.
  • Metastasis-directed therapy (MDT): Highly focused external radiation beams for oligometastatic deposits.

What happens if a patient is positive on a genetic test for prostate cancer?

Genetic test results enable targeted therapies:

  • BRCA1/BRCA2 mutations: Doublet therapy plus a PARP inhibitor such as olaparib (Lynparza) or rucaparib (Rubraca).
  • Microsatellite instability: Eligible for pembrolizumab (Keytruda).

How is the outlook for metastatic prostate cancer changing?

Prognosis for metastatic prostate cancer has improved dramatically. It is now common for men to live 10 years or longer with metastatic disease. Additionally, radiation directed at the primary prostate gland in patients with metastatic cancer has shown survival benefits and is increasingly incorporated into treatment plans.

Any final notes?

Men should undergo a cardiac evaluation before starting hormonal therapy, as these treatments can exacerbate cardiovascular risk factors. Addressing heart health before and during treatment is essential.