JU INSIGHT Estimating the Effect of Radical Prostatectomy

By: Andrew Vickers, PhD, Memorial Sloan Kettering Cancer Center, New York, New York; Emily Vertosick, MA, Memorial Sloan Kettering Cancer Center, New York, New York; Lisa Langsetmo, MD, PhD, Minneapolis VA Health Care System, Minnesota, University of Minnesota, Minneapolis; Philipp Dahm, MD, Minneapolis VA Health Care System, Minnesota, University of Minnesota, Minneapolis; Gunnar Steineck, PhD, University of Gothenburg, Sweden; Timothy J. Wilt, MD, MPH, Minneapolis VA Health Care System, Minnesota, University of Minnesota, Minneapolis | Posted on: 14 Aug 2024

Vickers A, Vertosick E, Langsetmo L, Dahm P, Steineck G, Wilt TJ. Estimating the effect of radical prostatectomy: combining data from the SPCG4 and PIVOT randomized trials with contemporary cohorts. J Urol. 2024;212(2):310-319. doi:10.1097/JU.0000000000004039

Study Need and Importance

Radical prostatectomy should only be performed in individuals having higher-risk prostate cancers and a sufficiently long life expectancy, such that surgery results in a sufficiently large decrease in mortality to justify the risk of urinary and erectile dysfunction. There is, however, a dearth of data that can inform an individual patient of their expected reduction in risk of mortality with surgery. Two randomized trials have had mature data published, SPCG4 and PIVOT, but applying their results to contemporary patients treated at a high-volume center requires a statistical modeling approach.

What We Found

We saw no evidence that the relative risk reduction of surgery varied by baseline 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 (Table).

Limitations

The current model does not incorporate the risk of death from other causes. This is planned for further research. The results are for high-volume surgeons at a major academic medical center; the benefits of surgery are likely lower in community settings.

Interpretation for Patient Care

Surgery should be avoided for men with low (GG1) risk 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.

Table. Fifteen-Year Prostate Cancer Death Estimates for Surgery and No-Surgery Groups for Various Levels of Baseline Biochemical Recurrence Risk, Along With Example Associated Patient and Disease Characteristics for That Risk Level

Preoperative BCR risk at 5 y	Example patient characteristics				Risk of prostate cancer death at 15 y (immediate surgery), %	Difference in risk of prostate cancer death at 15 y, %
Preoperative BCR risk at 5 y	Clinical Gleason Grade Group	Age (y)	PSA (ng/mL)	Clinical T stage		HR 0.75	HR 0.65	HR 0.55	PIVOT surgery arm	HR 0.33	HR 0.2
5%	1	60	4	T1	0.2	0.2	0.2	0.2	0.2	0.2	0.2
10%	2	61	3	T1	0.2	0.2	0.2	0.2	0.2	0.2	0.2
15%	2	60	5	T1	1.2	0.5	0.7	1.0	3.3	2.3	4.3
20%	2	63	8	T1	2.9	0.9	1.5	2.3	7.8	5.6	11
30%	2	62	10	T2A	4.8	1.5	2.5	3.7	9.6	9.0	17
40%	3	64	8	T1	7.8	2.5	3.9	5.9	9.9	14	26
50%	4	66	8	T1	12	3.8	6.0	9.0	8.4	21	36
Abbreviations: BCR, biochemical recurrence; HR, hazard ratio. To illustrate the table, we will use the example of a patient with a risk of BCR of 40% at 5 years (penultimate row). The “example patient characteristics” show that a 64-year-old with a PSA of 8 ng/mL, T1, Grade Group 3 has a risk of recurrence of about 40%. This is just an example as, naturally, other combinations of stage, grade, and PSA would be close to 40% risk. A surgically treated patient with a 40% risk of BCR has an estimated 15-year risk of death from prostate cancer of 7.8%. Excluding the 2 most extreme scenarios, this is an absolute risk reduction of between 3.9% and 14% depending on assumptions, that is, risk of death without immediate surgery is somewhere between 12% and 22%.