Table 1.
Projection of Ovarian 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 | ||||
|---|---|---|---|---|
| Type I | Type II | Total | ||
| (A) | Years of follow-up | 10 | ||
| (B) | Annual Incidence Hazard | 0.001 | ||
| (C) | Distribution of Cases | |||
| Early Stage | 26% | 13% | 39% | |
| Late Stage | 10% | 52% | 61% | |
| Total | 35% | 65% | 100% | |
| (D) | Annual Mortality Hazard | |||
| Early Stage | 0.016 | 0.041 | 0.024 | |
| Late Stage | 0.125 | 0.174 | 0.165 | |
| Total | 0.037 | 0.133 | 0.090 | |
| Box 2: Mortality Reduction Projection | ||||
| Type I | Type II | Total | ||
| (E) | Stage Shift Multiplier | 0.610 | 0.597 | 0.690 |
| (F) | Stage Shift | 5% | 25% | 30% |
| Mortality Reduction | ||||
| (G) | Projected Ignoring Type | 21% | ||
| (H) | Projected Preserving Type | 3% | 15% | 18% |
| (I) | Absolute Difference | +3% | ||
| (J) | Relative Difference | +15% | ||
(A) Years of follow-up for hypothetical trial
(B) Annual incidence hazard of ovarian cancer estimated from SEER (18 registries, Nov 2020 submission) for women ages 50–54 years in 2000–2009
(C) Distribution of cases from Pavlik et al. [6]
(D) Hazard of mortality following diagnosis, derived from 100-month survival rates presented in from Pavlik et al. [6], 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 subtypes combined, and then separately by subtype 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 subtypes proportional to late-stage case mix (C).
(G) = (E) × (F) in total
(H) = (E) × (F) for each subtype separately and summed across subtypes
(I) and (J) Absolute and relative differences of projection in total compared to projection by subtype