A Framework for Treatment Decision Making at Prostate Cancer Recurrence

Abstract

Background Of the 50,000 men in the US who elect radical prostatectomy for prostate cancer, 24–40% will have a prostate-specific antigen (PSA) recurrence (PSA-R) within 10 years. Deciding whether to administer salvage therapy (ST) at PSA-R presents challenges, as treatment reduces risk of progression to clinical metastasis but incurs unnecessary side effects should the man die before metastasis. We develop a new harm-benefit framework using a clinical cohort to inform shared decision-making between patients and physicians at PSA-R. Methods Records of 1,045 Johns Hopkins University Hospital patients diagnosed in 1984–2013 who had PSA-R following radical prostatectomy were analyzed using marginal structural models to estimate the baseline risk of metastasis and the effect of ST (radiation therapy with or without hormone therapy) while accounting for selection into ST on the basis of PSA growth. The estimated model predicts harm-benefit tradeoffs of ST within patient subgroups. Benefit of ST is the absolute reduction in the risk of metastasis within 10 years; harm is the frequency of cancers that would not have metastasized in the patient's lifetime in the absence of ST (overtreatment). Results The adjusted hazard ratio associated with ST was 0.41 (95% CI 0.31 to 0.55). Providing ST to all men at PSA-R reduced risk of metastasis from 43% to 23% but led to 31% of men being overtreated (harm/benefit=31/(43-23)=1.6). Providing ST to men with Gleason score >7 reduced risk of metastasis from 67% to 39% with 13% of men being overtreated (harm/benefit=13/(67-39)=0.5). Conclusions A quantitative framework that evaluates primary harms and benefits of ST after PSA-R will facilitate informed decision-making. Immediate ST may be more appropriate in patient subgroups at elevated risk of metastasis.

Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts

“…Sensitivity analyses considered each of the following: A strong correlation between the times to underlying upgrade, metastasis, and death, achieved by assuming that the times to metastasis and death share the same percentile as the time to underlying upgrade, conditional on age and PSA at diagnosis. An enhanced benefit of primary treatment on the time to metastasis, corresponding to treatment such as adjuvant or salvage radiation. Salvage radiation in patients who undergo RP is associated with an HR of 0.41, so we assessed a benefit of combined surgery and radiation of 0.53 * 0.41 = 0.23. …”

68Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy – diagnostic performance and impact on therapeutic decision-making

“…Management of patients with PSA-only recurrence [i.e., biochemical recurrence (BCR)], is a clinical challenge as some may have localized disease only potentially benefiting from local therapy. Avoidance of overtreatment with its unnecessary side effects while ensuring effective durable disease control remains dependent on identification of the site of disease recurrence [ 4 ]. Indeed, early salvage treatment can confer durable local disease control, prolonging survival [ 5 – 7 ].…”

Impact of cancer screening on metastasis: A prostate cancer case study

“…In the first sensitivity analysis, we examined the possibility that screening may confer an additional benefit beyond just the stage shift on the risk of progressive metastasis. 15 In the second sensitivity analysis, we reduced the risk of progressive metastasis in treated men on both arms to accommodate adjuvant or early salvage treatments for PSA recurrence that might not have been present in the SPCG-4 cohort. In the third sensitivity analysis, we addressed the possibility that risk of metastasis after diagnosis may be very different for today's cancer patients as compared to the SPCG-4 trial.…”