If you were a kid in the 1960s, you may recall listening to the exciting audio countdown for NASA’s first rocket launches: “Liftoff at T minus 10 seconds. 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, zero…and we have liftoff!” Since then, zero has been dropped from the countdown. In fact, it has no meaning as a counting number, which is why you learned how to count starting with the number 1 when you were little.

However, if you are a prostate cancer (PCa) patient who had a prostatectomy, zero has a key meaning. Once your prostate is removed, it is expected that your PSA will soon drop to an undetectable level. When a follow-up PSA blood test registers 0.0 ng/mL, it means no more PCa! Surgery got it all. (NOTE: today’s PSA lab tests are so sensitive that sometimes a very, very low level of PSA is picked up. This is not concerning, as long as it does not rise.)

Nonetheless, your doctor continues to monitor for recurrence by means of the PSA blood test at regular intervals, as prescribed. Without a prostate gland to produce PSA, your PSA should remain undetectable for the rest of your life—unless the surgery did not get all the cancer. You see, PCa cells produce PSA because they are mutated prostate cells. If cancer cells had already escaped the gland and begun to multiply somewhere else, these residual cells will start producing enough PSA to circulate in the blood. Thus, a monitoring blood test picks up this activity and registers a rising number above zero.

This is why many post-prostatectomy patients grow anxious as time nears for their next monitoring PSA test. If the result is still zero, they can stop sweating. But if it’s starting to increase, it’s called biochemical recurrence (BCR) because PSA is a biomarker for the presumed existence of cancer cells that are producing PSA. The idea that PCa was never entirely eradicated and is now active somewhere in the body strikes fear. “Does this mean I’m going to die?” wonders the scared patient.

Not a sentence of doom

The patient’s doctor can reassure him that his rising PSA is not a death sentence. The patient is more likely to die of other causes, especially if his PCa was low-risk. A Sep. 2023 paper published in the Journal of the American Medical Association (JAMA) should help ease prostatectomy patients’ worries because it reports a very low risk of dying from PCa in spite of BCR.^[i]

The research involved a large international multi-center study by some of the top cancer centers in the U.S. and Europe, including MD Anderson (Houston, TX) and the Icahn School of Medicine at Mt. Sinai (New York, NY). The research team had data from 10,364 prostatectomy patients who were followed after surgery by means of PSA tests. The study period was 2003 – 2019, and the average follow-up time was over seven years. Patients were stratified by risk group, defined as:

Low risk (4024 patients)	Intermediate risk (5239 patients)	High risk (1101 patients)
PSA < 10 ng/mL And Gleason score < 7 And Stage T1-2a	PSA 10-20 ng/mL Or Gleason score 7 Or Stage T2b	PSA > 20 ng/mL Or Gleason score > 7 Or Stage T2c

The authors found the following percentages of BCR detected during follow-up, and calculated the associated risks of BCR patients dying specifically from their prostate cancer:

	Low risk	Intermediate risk	High risk
BCR 15-year occurrence rate	16%	30%	46%
PCa specific 10-year mortality rate	4%	[not reported]	9%

Compared with patients who did not have BCR, falling in the high risk BCR category was a significant factor in PCa-specific mortality.

The odds are in your favor

If this large, multicenter analysis is representative of prostatectomy patients in general—and there is no reason to assume it isn’t—an overall view of the numbers shows why BCR after prostatectomy should not cause undue alarm.

• The majority of the patients (89%) were low-to-intermediate risk
• For those who experienced BCR, the greatest chance of PCa-specific death was 9% at 10 years, and that was for the patients with the highest disease risk level.

In particular, the authors write, “We found that patients falling in the low-risk BCR category after radical prostatectomy had a similar risk of [PCa-specific mortality] compared with patients with no BCR and may be considered as patients with nonclinically significant recurrence.” In other words, a low-risk prostatectomy patient with BCR has roughly the same survival benefit as one who has no BCR after surgery.

The importance of this study lies in stratification. It illustrates the advantage of diagnosis and treatment when PCa is low risk, implying the importance of early detection. This principle holds for any treatment, including focal therapies. In addition, accurate diagnosis that includes multiparametric MRI and real time MRI-guided targeted biopsy enables best treatment matching. For patients considering robotic prostatectomy, our services can shed light on probable outcome. Contact us to learn more.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Falagario UG, Abbadi A, Remmers S, et al. Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy. JAMA Netw Open. 2023;6(9):e2332900.