When to use radiation therapy after Surgery for Prostate Cancer

Czech study Results on using uPSA to determine when to use radiation
after Radical Prostatectomy

Radiation Decision pints

When should the patient and doctor consider salvage radiation therapy? | THE "NEW" PROSTATE CANCER INFOLINK
definitions of some commonly used terms and abbreviations:

• Aggressive pathology means that the post-op pathology report indicates that cancer was found in one or more of the following places:
  • Outside of the prostate capsule (pathological stage T3a), or
  • In the seminal vesicles (pathological stage T3b), or
  • Locally, but at a distance from the prostate (pathological stage T4), or
  • At the surgical margin, where the surgeon has cut through the cancer — a “positive surgical margin” (PSM).
• Adjuvant radiation therapy (aRT) start right away.
• Salvage radiation therapy (sRT) start after BCR.
• Early salvage radiation therapy (early sRT) after aRT, but before sRT .
• Wait-and-see .
• Biochemical recurrence (BCR) post-surgery is now defined as a confirmed PSA ≥ 0.2 ng/ml. .
• An ultrasensitive PSA (uPSA) test is any PSA test that can reliably detect PSAs below 0.1 ng/ml. While the definition of biochemical recurrence has not been changed, detectable levels of PSA are now as low as 0.001 ng/ml on some commercially available ultrasensitive tests.

Ultrasensitive PSA reliably predicts eventual biochemical recurrence (a UCLA study)

Kang et al. found that a uPSA ≥ 0.03 ng/ml was the optimal threshold value for predicting biochemical recurrence (BCR). Other findings included:

• uPSA ≥ 0.03 ng/ml was the most important and reliable predictor of BCR. It predicted all relapses (no false negatives: no one was under-treated), and hardly ever predicted relapses incorrectly. Only 2 percent would be over-treated by waiting for this cut-off.
• It was especially prognostic if found on the first uPSA test after surgery.
• Even if the first uPSA test was undetectable, any subsequent test where uPSA ≥ 0.03 ng/ml predicted BCR.
• Other lesser predictors of recurrence were pathologic Gleason grade, pathologic T stage, initial PSA before surgery, and surgical margin status.
• At 5 years of follow-up, 46 percent of patients had a BCR using the “standard” PSA ≥ 0.2 definition, 76 percent using the PSA ≥ 0.03 definition.
• Treating when an ultrasensitive PSA level reached 0.03 ng/ml gave a median lead time advantage of 18 months over waiting until PSA reached 0.2 ng/ml.
• It was necessary to monitor PSA for at least 5 years post-op, and to test at least every 6 months.

Ultrasensitive PSA can reliably predict eventual biochemical recurrence at 2 months after surgery (a Czech study)

A Czech study (Vesely et al.) looked at a group of 116 patients who had PSMs after surgery. Unlike the UCLA study, staging was not a selection criterion. The two studies’ goals were somewhat different. While the UCLA study didn’t start uPSA testing until 3 months after prostatectomy, in this study uPSA testing was begun at 2 weeks post-surgery. Most urologists wait for 3 months because surgery sheds a lot of PSA into the serum, and it takes a while for that excess to clear out. The goal in this study was to find out just how early in time after prostatectomy they could detect a uPSA prognostic for BCR, whereas the UCLA study sought to find out how late in uPSA progression they could detect a PSA prognostic for progression. The Czech cohort had the following characteristics:

• Only patients with PSMs were included
• Patients who received aRT or hormone therapy were excluded
• Pathological stage T3/T4 in 54 percent of patients
• Gleason score ≥ 7 in 51 percent of patients
• Initial, pre-surgical PSA ≥ 9.2 in 50 percent of patients
• Time to first post-op PSA, 14 days

All patients’ PSA levels were measured on days 14, 30, 60, 90, and 180 post-surgery, and at 3-month intervals thereafter; the median follow-up was 31 months.
Vesely et al. found that the uPSA on day 30 had predictive accuracy of 74 percent for recurrence, and reached a maximum of 84 percent by day 60, when the uPSA was 0.04 ng/ml (increases in accuracy afterwards were not statistically significant). The following table summarizes their findings: