The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group

Abstract

Purpose: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study.

Experimental design: We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing.

Results: The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005).

Conclusions: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated.

Figure 1

Predicted probability of prostate cancer with increasing PSA, separately by cohort. Legend:

1. Cleveland Clinic

2. Durham VA

3. SABOR

4. PCPT

5. Tyrol

6. Göteborg rounds 2 to 6

7. ProtecT

8. Rotterdam rounds 2 to 3

9. Rotterdam round 1

10. Göteborg round 1

11. Tarn

Panel A: Prediction of prostate cancer Panel B: Prediction of prostate cancer for men with negative DRE, non-African origin, and no prior biopsy. Note that ProtecT and Durham are excluded because DRE result was not available for the majority of men biopsied in those cohorts. The SABOR cohort includes only a very small number of men with PSA > 7 (n=16), and sampling variation likely explains the apparent reduction in risk above PSA of 7. Panel C: Prediction of high grade prostate cancer for men with negative DRE, non-African origin, and no prior biopsy. Note that ProtecT and Durham are excluded because DRE result was not available for the majority of men biopsied in those cohorts; Göteborg round 1, Tarn and SABOR are excluded due to low numbers of high grade cancers. The risk from the PCPT risk calculator was determined for a man age 65 at biopsy, which was close to the mean age of the entire cohort.

Figure 1

Predicted probability of prostate cancer with increasing PSA, separately by cohort. Legend:

1. Cleveland Clinic

2. Durham VA

3. SABOR

4. PCPT

5. Tyrol

6. Göteborg rounds 2 to 6

7. ProtecT

8. Rotterdam rounds 2 to 3

9. Rotterdam round 1

10. Göteborg round 1

11. Tarn

Panel A: Prediction of prostate cancer Panel B: Prediction of prostate cancer for men with negative DRE, non-African origin, and no prior biopsy. Note that ProtecT and Durham are excluded because DRE result was not available for the majority of men biopsied in those cohorts. The SABOR cohort includes only a very small number of men with PSA > 7 (n=16), and sampling variation likely explains the apparent reduction in risk above PSA of 7. Panel C: Prediction of high grade prostate cancer for men with negative DRE, non-African origin, and no prior biopsy. Note that ProtecT and Durham are excluded because DRE result was not available for the majority of men biopsied in those cohorts; Göteborg round 1, Tarn and SABOR are excluded due to low numbers of high grade cancers. The risk from the PCPT risk calculator was determined for a man age 65 at biopsy, which was close to the mean age of the entire cohort.

Figure 1

Predicted probability of prostate cancer with increasing PSA, separately by cohort. Legend:

1. Cleveland Clinic

2. Durham VA

3. SABOR

4. PCPT

5. Tyrol

6. Göteborg rounds 2 to 6

7. ProtecT

8. Rotterdam rounds 2 to 3

9. Rotterdam round 1

10. Göteborg round 1

11. Tarn

Panel A: Prediction of prostate cancer Panel B: Prediction of prostate cancer for men with negative DRE, non-African origin, and no prior biopsy. Note that ProtecT and Durham are excluded because DRE result was not available for the majority of men biopsied in those cohorts. The SABOR cohort includes only a very small number of men with PSA > 7 (n=16), and sampling variation likely explains the apparent reduction in risk above PSA of 7. Panel C: Prediction of high grade prostate cancer for men with negative DRE, non-African origin, and no prior biopsy. Note that ProtecT and Durham are excluded because DRE result was not available for the majority of men biopsied in those cohorts; Göteborg round 1, Tarn and SABOR are excluded due to low numbers of high grade cancers. The risk from the PCPT risk calculator was determined for a man age 65 at biopsy, which was close to the mean age of the entire cohort.

Figure 2

Effects of biopsy scheme. ProtecT (10 cores) vs ERSPC Göteborg and Rotterdam (6 cores)

Figure 3

Effects of previous PSA screening. Göteborg and Rotterdam round 1 (both with no previous screening) vs Göteborg rounds 2–6 and Rotterdam rounds 2–3 (all had previous screening)