Prostate Cancer Survivorship: Follow-Up Questions

Almost everything in prostate cancer follow-up hangs on one number.

After radical prostatectomy the prostate is gone. PSA should fall to nothing. NCI's summary uses 0.2 ng/mL or higher as evidence of biochemical recurrence.

After radiation the prostate is still there, so PSA does not go to zero. The definitions of failure vary between published series. NCI notes that criteria were developed by an American Society for Therapeutic Radiology and Oncology consensus panel, and that the effect of the different definitions on overall survival is not known.

That is worth hearing plainly. The threshold after surgery is fixed. After radiation it is a matter of which definition a center uses.

The word "recurrence" lands hard. The timeline behind it is often much longer than people expect.

NCI cites a retrospective analysis of nearly 2,000 men. All had radical prostatectomy with curative intent. They were followed for a mean of 5.3 years. Of those, 315 men, or 15%, reached a PSA of 0.2 ng/mL or higher.

Of those 315, 103 went on to clinical recurrence. That is 34%. Two thirds did not, within that follow-up.

The intervals are the part worth carrying. Median time from biochemical recurrence to clinical metastasis was 8 years. After metastasis appeared, median time to death was a further 5 years.

NCI states the general point too. A substantial proportion of men with elevated or rising PSA after treatment with curative intent stay free of symptoms for extended periods.

NCI's PSA fact sheet adds a caution that gets lost in the anxiety of a result.

A single elevated PSA measurement in someone with a history of prostate cancer does not always mean the cancer has come back. The advice is to discuss it, and the doctor may repeat the test or order others. What is being looked for is a trend of rising values over time, not one number.

That is also why the assay matters. Some labs run ultrasensitive PSA tests that report far below 0.2 ng/mL. Asking what a particular lab counts as undetectable makes the numbers comparable from visit to visit.

The complications of radical prostatectomy are listed directly by NCI: urinary incontinence, impotence, penile shortening, inguinal hernia and fecal incontinence.

Numbers vary a lot by series and by surgeon. That variation is itself worth asking about, because a national average may not describe one center.

In a large case series using the nerve-sparing technique, about 6% of men needed pads for urinary incontinence, though an unknown further proportion had occasional dribbling. Between 40% and 65% of men who were potent before surgery kept potency adequate for intercourse.

NCI also notes that functional outcomes for sexual, urinary and bowel function look similar whether the operation is open retropubic, laparoscopic or robot-assisted. Robot-assisted surgery is now the most common technique in developed countries. It is not, on this evidence, a different recovery.

External-beam radiation has a different profile. NCI lists acute cystitis, proctitis and enteritis. These are generally reversible, though they can become chronic, and rarely need surgery.

The most useful comparison comes from a community-based cohort of men aged 55 to 74. The figures were adjusted for baseline differences. Early on, surgery was linked to more heart and lung complications, 5.5% against 1.9%. It also brought more treatment for urinary strictures, 17.4% against 7.2%. Radiation brought more acute rectal proctitis, 18.7% against 1.6%.

For chronic effects, surgery carried more urinary incontinence, 9.6% against 3.5%, and more impotence, 80% against 62%. Radiation carried slightly greater declines in bowel function.

Those figures are group averages from one cohort. They are still more useful than a general statement that both treatments have side effects.

Androgen deprivation is sometimes started for a rising PSA. One trial changed how it is given.

NCI describes a noninferiority trial of 1,386 men with a PSA above 3 ng/mL more than a year after radiation. They received either continuous androgen deprivation or intermittent cycles, restarted when PSA rose above 10 ng/mL.

After a median follow-up of 6.9 years, survival was nearly identical: median 8.8 years on intermittent against 9.1 years on continuous. Intermittent met the criterion for noninferiority.

It also did better on several quality-of-life measures, including hot flashes, desire for sexual activity and urinary symptoms. Men on the intermittent arm received a median of 15.4 months of treatment, against 43.9 months on continuous.

One statistic there deserves to be read twice. In that trial, 59% of all deaths were unrelated to prostate cancer. Fourteen percent of all patients died of it.

Not every biochemical recurrence is slow. Speed changes the options.

NCI describes the phase III EMBARK trial. It enrolled 1,068 men who had already had surgery or radiation with curative intent. All had a rapidly rising PSA. None were candidates for further pelvic salvage treatment.

They were assigned to one of three arms. Enzalutamide, taken daily as a tablet, together with leuprolide. Placebo with leuprolide. Or enzalutamide alone.

After 60.7 months of follow-up, five-year metastasis-free survival was 87.3% for the combination, against 71.4% for leuprolide alone. The hazard ratio was 0.42. Enzalutamide on its own reached 80.0%.

The point for follow-up is not the drug names. It is that PSA doubling time is doing real work in these decisions, which is why teams track the rate rather than the single value.

For the disease itself, see prostate cancer. For life after treatment more broadly, see survivorship and watching for cancer recurrence.

• NCI PDQ — Prostate Cancer Treatment (Health Professional Version)
• NCI — Prostate-Specific Antigen (PSA) Test