After being diagnosed with prostate cancer, many men will undergo treatment with either surgery or radiotherapy. While both of these treatments are highly effective, a cure is not guaranteed. Thus, doctors monitor men following prostate cancer treatment with periodic checks of the PSA blood test (typically every three months for the first year, every six months for years 2 and 3, and annually thereafter). PSA is a very useful marker in men who have undergone prostate cancer treatment. When PSA levels rise following prostate cancer treatment, we call this “biochemical recurrence.”

For men who initially had a radical prostatectomy (surgery to remove the prostate gland) as their primary prostate cancer treatment, the PSA level should go down to an undetectable level after surgery. Depending on the laboratory used, this may be recorded as values less than < 0.2 ng/mL, <0.1 ng/mL, <0.05 ng/mL, <0.01 ng/mL or < 0.008 ng/mL. For patients treated with surgery, biochemical recurrence is typically defined as a PSA level of at least 0.2 ng/mL. Sometimes, an increased PSA level may be a false result. Because of this, most definitions of biochemical recurrence (including those of the American Urological Association) require confirmation with a second test.

When there is biochemical evidence of prostate cancer returning (that is, the PSA level is rising), we must distinguish between “biochemical only” recurrence (a rising PSA blood test without any evidence of cancer on physical examination or imaging tests) and “clinical” recurrence (evidence of cancer on physical examination or imaging tests). When PSA levels are low (<1 ng/mL), clinical recurrence is very uncommon and many clinicians will not order imaging tests. However, increasing use of PSMA-PET imaging, may allow for the identification of specific spots of disease, even when the PSA is as low as ~0.05 ng/mL.

For men who have received surgery as their first prostate cancer treatment, salvage radiotherapy is the standard treatment approach at the time of biochemical recurrence. Salvage radiotherapy is typically given to the “prostate bed” (where the prostate used to be before surgery) and may also include the region of the pelvic lymph nodes. Many studies have shown that salvage radiotherapy is the best chance at a long-term cure.

Early salvage radiotherapy (performed when PSA levels are low, ideally around 0.2- 0.4ng/mL) is more effective than if radiotherapy is delayed and the PSA is allowed to rise higher before treatment starts. Some studies have shown a benefit to adding androgen deprivation therapy (ADT) at the time of salvage radiotherapy. However, there is some controversy about how helpful it is in men who are receiving early salvage radiotherapy. Often, the PSA level at the time of starting salvage radiotherapy as well as patient characteristics (age and other illnesses), and initial cancer details (including PSA at the time of diagnosis, Gleason score, and tumor stage from surgery) are used to inform this decision.

With the increasing use of PSMA-PET/CT and the identification of sites of disease, targeted radiation (stereotactic body radiotherapy, SBRT) is increasingly becoming an option for treating these spots in addition to the standard salvage radiation approach. However, it should be re-emphasized that for early biochemical recurrence (PSA <0.2 ng/mL and up to even 0.4 ng/mL), imaging is typically not necessary prior to starting salvage radiotherapy given that the ability of even the best imaging modality (i.e., PSMA PET CT scan) to detect specific spots of disease is still somewhat limited.

In conclusion, while all men (and their physicians) hope that the first prostate cancer treatment will be the last, recurrence is not uncommon. Thankfully, there are effective treatment options. For men who have surgery as their first prostate cancer treatment, salvage radiotherapy is a proven effective treatment.

Zachary Klaassen, MD, MSc
Urologic Oncologist, Georgia Cancer Center, Augusta University, Augusta, GA, USA