Prostate Cancer Risk Assessment and the UCSF-CAPRA Score

Prostate Cancer Risk Assessment and the UCSF-CAPRA Score

Prostate cancer is the most common cancer diagnosed among American men, and causes more deaths annually among men than any other tumor except lung cancer. However, only a small proportion of prostate cancers diagnosed are ultimately lethal. A large majority of men found to have prostate cancer ultimately die of other causes, most commonly cardiovascular disease. All available treatments for prostate cancer (surgery, radiation therapy, hormonal therapy, and others) carry a risk of complications, side effects, and other impacts to the patient's long-term quality of life. Before making a decision regarding treatment for prostate cancer it is important to estimate the likelihood that a given tumor will recur after treatment, progress, and pose a threat to life.

Risk Assessment Methods

Risk Assessment systems are not intended to replace individualized clinician-patient decision making, but rather to provide a straightforward instrument for facilitating disease risk classification in clinical decision making and in future research.

There are many approaches to risk assessment including the D'Amico classification, a variety of nomograms and the UCSF-CAPRA Score.

Risk classification (D'Amico): The classification developed by D’Amico and colleagues is one of the most widely used and is a good starting point for risk assessment. This system uses PSA level (blood test), Gleason grade (microscopic appearance of the cancer cells), and T stage (size of the tumor on rectal exam and/or ultrasound) to group men as low, intermediate, or high-risk.

Low-risk: PSA less than or equal to 10, Gleason score less than or equal to 6, and clinical stage T1-2a
Intermediate risk: PSA between 10 and 20, Gleason score 7, or clinical stage T2b
High-risk: PSA more than 20, Gleason score equal or larger than 8, or clinical stage T2c-3a

Limitations: Does not account for multiple risk factors

For example, 
Patient one: Gleason 3+4, PSA 3.2, stage T1c cancer in one biopsy core
Patient two: Gleason 4+3, PSA 19.2, stage T2b cancer involving eight cores

• Both patients are classified as intermediate risk, althought patient two would have much higher disease risk.

Nomograms: Pioneered in prostate cancer by Kattan and colleagues is an approach that incorporates multiple risk variables to produce mathematical models that predict the likelihood of disease recurrence or progression. The models are often presented as nomograms, graphical calculating devices that allow determination of the score based on values presented on a paper table. Many such instruments have been developed for prostate cancer. Memorial Sloan-Kettering Cancer Center provides an on-line calculator which allows some of the models to be calculated. A few of these nomograms are well known and have been validated in multiple settings.

Limitations: care must be taken in interpreting the predictions from the calculators.

For example,
• A model developed using data from patients treated by a high-volume surgeon in a large city, may not be valid for those treated by a lower-volume surgeon in rural area. In general, nomograms developed using data from academic series tend to be somewhat overly optimistic when applied in the community practice setting.

• Each nomogram is developed using a different set of patients in a different setting, and usually using different definitions of cancer recurrence or progression. Because the definitions of recurrence and progression are not consistent across nomograms, scores from the different treatment nomograms (e.g. pre-prostatectomy and pre-brachytherapy) cannot be used to compare the likelihood of a good result from one type of treatment versus another type of treatment for an individual man. Each nomogram is deisgned to give a prediction of treatment success only after a treatment decision has already been made.

The UCSF-CAPRA score

In a effort to address the limitations of these approaches to risk assessment UCSF developed the Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score. CAPRA is a straightforward 0 to 10 score. It is nearly as easy to calculate as the D’Amico classification, yet with accuracy comparable to the best nomograms. A CAPRA score is valid across multiple treatment approaches and it predicts an individual's likelihood of metastasis, cancer-specific mortality, and overall mortality.

The score is calculated using points assigned to: age at diagnosis, PSA at diagnosis, Gleason score of the biopsy, clinical stage and percent of biopsy cores involved with cancer. These variables are outlined below.

Variable Specific patient's level Points to be assigned

Age at diagnosis

Under 50 0
50 or older 1

PSA at diagnosis (ng/ml)

less than or equal to 6 0
between 6.1 and 10

1

between 10.1 and 20 2
between 20.1 and 30 3
more than 30 4

Gleason score of the biopsy
(primary/secondary)

no pattern 4 or 5 0
secondary pattern 4 or 5 1
primary pattern 4 or 5 3

Clinical stage (T-stage)

T1 or T2 0
T3a 1

Percent of biopsy cores involved with cancer (positive for cancer)

less than 34 percent 0
34 percent or more 1
 
 
 

 

How UCSF-CAPRA score is determined:

Example patient one: A 51 year old man with a PSA of 6.2, a Gleason score of3+4, and stage T2c prostate cancer involving 2 of 8 biopsy cores (25%) would have a score of 3.

Five variables to be analized:
Age at diagnosis = 51
PSA at diagnosis = 6.2
Gleason score of the biopsy (primary/secondary) = 3+4 (3/4) 
Clinical stage (T-stage) = T2c
Percent of biopsy cores involved with cancer (positive for cancer) = 2 of 8 (25%) 

Assigned scores for each variable from chart above: 
51 = 1
6.2 = 1 
3/4 = 1 
T2c = 0 
25% = 0 

CAPRA score is equal to the sum of the individual variables:
 1+1+1+0+0 = 3  

Patient one has a CAPRA score equal to 3

Example patient two: A 48 year old man with a PSA of 15.2, a Gleason score of 4+3, and stage T1c prostate cancer involving 5 of 10 cores (50%) would have a score of 6.

Five variables to be analized:
 Age at diagnosis = 48 
PSA at diagnosis = 15.2
Gleason score of the biopsy (primary/secondary) = 4+3 (4/3) 
Clinical stage (T-stage) = T1c
Percent of biopsy cores involved with cancer (positive for cancer) = 5 of 10 (50%) 

Assigned scores for each variable from chart above:
 48 = 0 
15.2 = 2 
4/3 = 3 
T1c = 0 
50% = 1 

CAPRA score is equal to the sum of the individual variables:
 0+2+3+0+1 = 6 

Patient one has a CAPRA score equal to 6

What does this score mean?

A CAPRA score of 0 to 2 indicates low-risk
A CAPRA score of 3 to 5 indicates intermediate-risk
A CAPRA score of 6 to 10 indicates high-risk

Very low-risk tumors are often managed well with active surveillance. Low to intermediate-risk tumors generally respond well to localized treatment (surgery or radiation alone, brachytherapy with or without external-beam therapy). Intermediate to high-risk tumors often require multimodal therapy (surgery with radiation, or radiation therapy with hormonal therapy). Very high-risk tumors may be treated with multimodal therapy or hormonal therapy alone, and often are suitable for clinical trials of new therapeutic approaches. Treatment decisions should be made in consultation with an appropriately trained physician.

How accurate is the UCSF-CAPRA system?
The UCSF-CAPRA score was developed using data from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). CaPSURE includes men treated across the country at one of 40 mostly community-based sites, so the results are applicable to “real-world” scenarios. The CAPRA score system has been tested by over 10,000 prostatectomy patients in multiple practice settings, and has been found to be accurate in predicting both pathologic outcomes after surgery and PSA recurrence after surgery. The studies showed that risk roughly doubles with every two point increase in CAPRA score. Updated data from CaPSURE have confirmed that the CAPRA score accurately predicts likelihood of metastasis, prostate cancer-specific survival and overall survival. Moreover, the new results are applicable not only to prostatectomy patients, but also to those undergoing radiation therapy (brachytherapy or external-beam), primary androgen deprivation therapy, cryoablation, or active surveillance.

In summary, risk assessment is a critical aspect of prostate cancer treatment decision-making. The CAPRA score offers a straightforward and accurate way for physcians and their patients to evaluate prosate cancer risk, and has been shown to predict pathologic stage, PSA recurrence, and distant outcomes (metastasis and mortality) following a range of treatment strategies.

The CAPRA scoring system is not intended to replace individualized clinician-patient decision making, but rather to provide a straightforward instrument for facilitating disease risk classification in clinical decision making and in future research.

For more information

  • Cooperberg, M.R., J.M. Broering, and P.R. Carroll, Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst, 2009. 101(12): p. 878-87. PubMed Link (ID:19509351)
  • Cooperberg, M.R., Prostate cancer risk assessment: choosing the sharpest tool in the shed. Cancer, 2008. 113(11): p. 3062-6. PubMed Link (ID:18855919), Full article PDF
  • Shariat, S.F., P.I. Karakiewicz, C.G. Roehrborn, and M.W. Kattan, An updated catalog of prostate cancer predictive tools. Cancer, 2008. 113(11): p. 3075-99. PubMed Link (ID:18823041)
  • Zhao, K.H., D.J. Hernandez, M. Han, E.B. Humphreys, L.A. Mangold, and A.W. Partin, External validation of University of California, San Francisco, Cancer of the Prostate Risk Assessment score. Urology, 2008. 72(2): p. 396-400. PubMed Link (ID:18372031)
  • May, M., N. Knoll, M. Siegsmund, D. Fahlenkamp, H. Vogler, B. Hoschke, and O. Gralla, Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients. J Urol, 2007. 178(5): p. 1957-62; discussion 1962. PubMed Link (ID:17868719)
  • Cooperberg, M.R., S.J. Freedland, D.J. Pasta, E.P. Elkin, J.C. Presti, Jr., C.L. Amling, M.K. Terris, W.J. Aronson, C.J. Kane, and P.R. Carroll, Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy. Cancer, 2006. 107(10): p. 2384-91. PubMed Link (ID:17039503), Full article PDF
  • Cooperberg, M.R., D.J. Pasta, E.P. Elkin, M.S. Litwin, D.M. Latini, J. Du Chane, and P.R. Carroll, The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy. J Urol, 2005. 173(6): p. 1938-42. PubMed Link (ID:15879786), Full article PDF

For more information about the UCSF-CAPRA score please contact Matthew Cooperberg, MD, MPH.