Extended mortality results for ovarian cancer screening in the PLCO trial with median 15years follow-up

Abstract

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial originally reported no mortality benefit of ovarian cancer screening after a median of 12.4years of follow-up. The UKCTOCS screening trial failed to show a statistically significant mortality reduction in the primary analysis but reported an apparent increased mortality benefit in trial years 7-14 compared to 0-7. Here we report an updated analysis of PLCO with extended mortality follow-up.

Methods: Participants were randomized from 1993 to 2001 at ten U.S. centers to an intervention or usual care arm. Intervention arm women were screened for ovarian cancer with annual trans-vaginal ultrasound (TVU) (4years) and CA-125 (6years), with a fixed cutoff at 35U/mL for CA-125. The original follow-up period was for up to 13years (median follow-up 12.4years); in this analysis follow-up for mortality was extended by up to 6years.

Results: 39,105 (intervention) and 39,111 (usual care) women were randomized, of which 34,253 and 34,304, respectively, had at least one ovary at baseline. Median follow-up was 14.7years in each arm and maximum follow-up 19.2years in each arm. A total of 187 (intervention) and 176 (usual care) deaths from ovarian cancer were observed, for a risk-ratio of 1.06 (95% CI: 0.87-1.30). Risk-ratios were similar for study years 0-7 (RR=1.04), 7-14 (RR=1.06) and 14+ (RR=1.09). The risk ratio for all-cause mortality was 1.01 (95% CI: 0.97-1.05). Ovarian cancer specific survival was not significantly different across trial arms (p=0.16).

Conclusion: Extended follow-up of PLCO indicated no mortality benefit from screening for ovarian cancer with CA-125 and TVU.

Figure 1

Deaths from ovarian cancer by arm and years from randomization. Red (solid) line is intervention arm, black (dotted) line is usual care arm. Numbers still at risk at selected time points are listed below the graph.

Figure 2

A) Ovarian cancer-specific survival by arm. Red (solid) line is intervention arm, black (dotted) line is usual care arm. B) Ovarian cancer-specific survival by mode of detection in the intervention arm. Red (solid) line is for screen detected cases, black (dotted) line is for non-screen detected cases. P-values (log-rank test) for difference in survival between arms and between screen detected and non-screen detected cases were 0.16 and 0.04, respectively.

Figure 2

A) Ovarian cancer-specific survival by arm. Red (solid) line is intervention arm, black (dotted) line is usual care arm. B) Ovarian cancer-specific survival by mode of detection in the intervention arm. Red (solid) line is for screen detected cases, black (dotted) line is for non-screen detected cases. P-values (log-rank test) for difference in survival between arms and between screen detected and non-screen detected cases were 0.16 and 0.04, respectively.