PSA Kinetics and Risk Factors

Identify and closely monitor your patients at risk to help determine the onset of metastatic prostate cancer

Risk Factors for Developing Metastatic Prostate Cancer After Biochemical Recurrence—Predictors of Postitive Bone Scans

Prostate-specific antigen (PSA) kinetics have evolved to the point that they can be used to help predict a man's risk of metastases at the time of biochemical recurrence after primary therapy. Specifically, PSA-DT* is an important kinetic useful in helping identify those at risk and in estimating the time to metastases.

Read on to learn how combining PSA value with PSA kinetics can be used to help identify patients at risk of metastases. PSA kinetics can be more helpful than using a PSA value alone to determine risk.

*Prostate-specific antigen doubling time (PSA-DT) is the time it takes for a PSA value to double after PSA returns to measurable levels following primary therapy.

Metastatic disease has been reported to develop within 3 years after RT (radiation therapy) with combined risk factors.1

Patients with biochemical recurrence within 1 year after RT and a PSA-DT of < 8 months (N=43) had particularly striking estimated metastatic disease rates.1

  • At 3 years, 50% of patients were projected to have developed metastases
  • At 6.5 years, 100% of patients were projected to have developed metastases
Estimated incidence of bone metastases in patients with clinical recurrence

Reprinted with permission from Zagars GK et al, Radiother Oncol. 1997.
*An actuarial method was used.

Study Design

In a retrospective analysis to determine PSA parameters in 841 patients with clinically localized or locally advanced prostate cancer, 263 patients were found to have rising PSA profiles after RT.1

Of these, 145 patients were found to have clinical recurrence (n=118 local, 7 pelvic nodal, 40 distant metastatic), as determined by bone scan, computerized tomography (CT), or biopsy. Based on these data, the actuarial rate of distant metastases was estimated.1

PSA Value and incidence of a positive bone scan after radical prostatectomy (RP)

Objective

Identify predictors of positive bone scans and create a risk evaluation tool.2 A nomogram utilizing multiple predictors was developed for estimating the probability of a positive bone scan.

PSA Value and the incidence of positive bone scan after radical prostatectomy (RP)

Adapted from: Dotan ZA, Bianco FJ Jr., Rabbani F, et al. J Clin Oncol. 2005;23:1962-1968.

Results

Of 414 bone scans in 239 patients, 60 scans (14.5%) were positive. On multivariate analysis, PSA kinetics (PSA slope and velocity) and PSA value before bone scan were predictors of positive bone scans. When a cut-off PSA value of 30 ng/mL before bone scan was used as the only predictor of a positive bone scan, the concordance index was 0.63. When the nomogram was used to predict the probability of a positive bone scan, the concordance index was 0.93.2

Study Design

Retrospective analysis of 4823 prostate cancer patients who underwent RP.2

  • 330 patients had increasing serum PSA after RP and underwent bone scans2
    • 239 hormone therapy-naïve patients were analyzed
    • Patients were also excluded from analysis if they received preoperative chemotherapy or RT

Important Considerations

Bone scans were performed and interpreted in multiple institutions. Bone scans were not performed at regular intervals, by protocol, but according to the discretion of the physician.2

Rapid PSA-DT can help predict positive bone scans3

The incidence of positive bone scans was 8 times greater for patients with a PSA-DT of < 6 months after RP vs patients with a PSA-DT > 6 months after RP.3

PSA-DT and incidence of positive bone scans

Adapted from: Okotie OT, Aronson WJ, Wieder JA, et al. J Urol. 2004;171:2260-2264.

PSA value coupled with rapid PSA-DT provides additional insight3

The likelihood of a positive bone or CT scan markedly increased in patients with a PSA-DT of < 6 months (n=31) when the PSA value at the time of the bone or CT scan was greater than 10 ng/mL.3

PSA-DT, PSA Value, and the incidence of positive bone or CT scans

Adapted from: Okotie OT, Aronson WJ, Wieder JA, et al. J Urol. 2004;171:2260-2264.

Study Design

In a retrospective analysis to determine the clinical predictors of positive bone scans and pelvic CT, 128 patients with Stage T2-T4 prostate cancer and biochemical recurrence after RP (mean time from RP to biochemical failure = 28 months) had pelvic CT and/or bone scans. A total of 97 bone scans and 71 CT scans were performed.3

The value of these data may be limited by the small sample size, the limited number of positive imaging studies, and the inability to standardize when PSA values were measured relative to imaging due to the retrospective nature of this analysis.3

Identify and closely monitor your patients at risk to help determine the onset of metastatic prostate cancer

Once patients have developed metastases, what is an appropriate treatment and what is the sequence of treatment?

References:

  1. This article was published in Radiother Oncol, 44, Zagars GK, Pollack A. "Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer," 213-221, Copyright Elsevier, 1997.
  2. Dotan ZA, Bianco FJ Jr., Rabbani F, et al. Pattern of prostate-specific antigen (PSA) failure dictates the probability of a positive bone-scan in patients with an increasing PSA after radical prostatectomy. J Clin Oncol. 2005;23:1962-1968.
  3. Okotie OT, Aronson WJ, Wieder JA, et al. Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. J Urol. 2004;171:2260-2264.