Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts

Abstract

Purpose: Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance.

Materials and methods: We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model.

Results: We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction).

Conclusions: Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

Keywords: prostate cancer; prostatectomy; statistical modeling.

Figure 1.

Predicted probability of prostate cancer death at 15 years by baseline risk, separately by cohort and for patients who were treated with radical prostatectomy (solid line) and those were managed conservatively (dotted line). Estimates for those without treatment in the MSKCC cohort were modeled using a hazard ratio of 0.55. The differences in risk of death for patients with the same stage, grade and PSA (as reflected in the nomogram risk on the x asis) reflect differences in patients and treatments, as discussed in the text. For instance, the difference in risk between PIVOT and SPCG4 watchful waiting arms (blue vs. green dotted lines) likely reflect stage shift associated with PSA screening, as more patients in PIVOT than SPCG4 had screen-detected cancers.

Figure 2.

Difference in predicted probability of prostate cancer death at 15 years between those who received surgery and those who did not by baseline risk, separately by cohort. Estimates for those without treatment in the MSKCC cohort were modeled using hazard ratios of 0.25, 0.33 and 0.55. Typical risk levels for an active surveillance patient (7%), low-intermediate risk patient (12%), high-intermediate risk patient (30%) and high-risk patient (60%) are also indicated. Green line: SPCG4. Blue line: PIVOT. Solid red line: MSKCC with hazard ratio for surgery of 0.55. Dotted red line: MSKCC with hazard ratio for surgery of 0.33. Dashed red line: MSKCC with hazard ratio for surgery of 0.25.