What happens if my PSA rises after radical prostatectomy? After external beam radiation therapy (EBRT)?After interstitial seed therapy?

When the PSA rises after definitive therapy, such as EBRT, interstitial seed therapy, and radical prostatectomy, it is called PSA progression. In the absence of any identifiable cancer, it is called biochemical progression, because the only indicator of progression of the cancer is the PSA level. When the PSA is increasing after definitive therapy, your physician may want to restage you to determine where the cancer is. It is helpful in the decision-making process to determine whether the prostate cancer is confined to the prostate (in men who have had interstitial seed therapy or EBRT), the area where the prostate was (in postradical-prostatectomy patients), or the pelvis, or whether it has spread outside of the prostatic area. For example, if it has spread to the bones or lymph nodes higher up in your abdomen. Methods used in this staging process may be a bone scan (see Question 12), a ProstaScint scan, and/ or a CT scan of the abdomen and pelvis. In certain cases, the doctor may recommend a biopsy of the prostate, of the bladder neck area, or of other areas that may be likely to have cancer.

After a radical prostatectomy your PSA should decrease to an undetectable level by approximately 4 weeks postoperative. However, a detectable PSA level after this time does not mean that there is necessarily clinically significant recurrent prostate cancer. Some patients with a detectable PSA after radical prostatectomy do not have progression of their cancer because the PSA level is the result of the presence of benign prostate tissue at the margins of the resection (a very small amount of benign prostate tissue being left behind) or from a dormant residual focus of prostate cancer at a local or distant site. The definition of biochemical recurrence (evidence of recurrent prostate cancer based on PSA testing only) varies from a PSA of 0.2 ng/ml to 0.4 ng/ml post radical prostatectomy. In a large number of patients a biochemical recurrence of 0.2 is associated with a slowly progressive course.

Your doctor will look at a variety of factors to determine if the rising PSA is caused by benign tissue left behind at the time of surgery, locally recurrent prostate cancer that is amenable to radiation therapy, or metastatic prostate cancer that will require hormone therapy. Several investigators have looked at various criteria that may help distinguish local recurrence from distant metastases for patients with a rising PSA after radical prostatectomy. A Gleason score 8-10, seminal vesicle invasion, positive lymph nodes and a rapid PSA velocity (rate of change of the PSA) and a short disease-free interval after radical prostatectomy have been associated with a greater chance of metastatic disease.

Overall, about 35% of men who have had a radical prostatectomy will experience a detectable serum PSA within 10 years after surgery. The risk of developing metastatic disease after biochemical recurrence correlates with pathologic Gleason scores. Men with tumors of Gleason score < 8 have a 73% chance of remaining free of progression at 5 years after biochemical recurrence, compared with a < 10% probability in men with high grade tumors (Gleason 8-10). The length of time after surgery prior to biochemical recurrence was important in determining the risk of eventual distant failure for men with lower (5-7) and men with higher (8-10) Gleason scores. Using a cutoff of 10 months, the prostate specific antigen doubling time (PSADT) provides further substratification for men with Gleason scores of < 8. Men with a rapid rise in PSA (shorter PSA doubling time) have a greater risk of metastatic disease.

Several options are available, including watchful waiting, salvage EBRT, and hormone therapy.