Table 2.
Projection of Prostate Cancer Mortality Reduction in a Hypothetical Screening Trial Ignoring and Preserving Subtypes According to their Distribution Among Late-Stage Diagnoses
| Box 1: Inputs to Mortality Reduction Projection | ||||
|---|---|---|---|---|
| Low Grade | High Grade | Total | ||
| (A) | Years of follow-up | 10 | ||
| (B) | Incidence Hazard | 0.005 | ||
| (C) | Distribution of Cases | |||
| Early Stage | 66% | 13% | 80% | |
| Late Stage | 8% | 13% | 20% | |
| Total | 74% | 26% | 100% | |
| (D) | Mortality Hazard | |||
| Early Stage | 0.017 | 0.087 | 0.026 | |
| Late Stage | 0.161 | 0.258 | 0.209 | |
| Total | 0.026 | 0.138 | 0.045 | |
| Box 2: Mortality Reduction Projection | ||||
| Low Grade | High Grade | Total | ||
| (E) | Stage Shift Multiplier | 0.399 | 0.292 | 0.437 |
| (F) | Stage Shift | 11% | 19% | 30% |
| Mortality Reduction | ||||
| (G) | Projected Ignoring Grade | 13% | ||
| (H) | Projected Preserving Grade | 5% | 5% | 10% |
| (I) | Absolute Difference | +3% | ||
| (J) | Relative Difference | +31% | ||
(A) Years of follow-up for hypothetical trial
(B) Incidence hazard of prostate cancer estimated from SEER (9 registries, Nov 2004 submission) for men ages 50–59 years in 1980–1984
(C) Distribution of cases from SEER for men diagnosed ages 50–59 years in 1980–1984
(D) Hazard of mortality following diagnosis, derived from SEER 10-year survival rates, assuming a constant hazard of mortality.
(E) Stage-shift multipliers calculated as in Owens et al. [5], see formulas G and H in that text. The inputs to these values are the length of follow-up (A), overall incidence rate of the disease (B), the rates at which the disease is diagnosed in each stage (C), and stage-specific survival rates (D). The calculation is performed with all grades combined, and then separately by grade using the corresponding inputs. This value is used below to convert a percent reduction in late-stage disease (F) to a percent reduction in disease-specific mortality (G, H).
(F) Percent reduction in late-stage cases. Hypothetical value of 30% in screening arm, allocated between grades proportional to late-stage case mix (C).
(G) = (E) × (F) in total
(H) = (E) × (F) for each grade separately and summed across grades
(I) and (J) Absolute and relative differences of projection in total compared to projection by grades