Active surveillance a safe, viable option for men with early-stage prostate cancer

Men on active surveillance (AS) appear to have favourable long-term prognosis, with a low risk of metastases and prostate cancer-specific death, according to a study.

“In the long term, AS is a safe and viable option for men with low risk and carefully selected intermediate-risk prostate cancer,” the researchers said.

However, the increased risk of metastases associated with higher Gleason grade, prostate specific antigen (PSA) velocity, and characteristics on multiparametric magnetic resonance imaging (MRI) should be considered when selecting and counseling patients for AS.

The researchers retrospectively reviewed data of men enrolled on AS between 1990 and 2018 with low- or intermediate-risk disease (stage cT1-2, PSA <20 ng/ml, biopsy Grade Group (GG) 1-2). They classified patients into three groups by diagnostic GG and PSA density.

Metastatic cancer detected on MRI or at prostatectomy was the primary outcome. Secondary outcomes included upgrade at surveillance biopsy, active treatment, and overall and prostate cancer-specific survival outcomes. Cox proportional hazards regression models were generated.

A total of 1,450 men were included in the analysis, with a median follow-up of 77 months (interquartile range [IQR], 49–114). The 7-year metastasis-free survival rate was 99 percent. Fifteen men developed metastasis at a median of 62 months (IQR, 29–104), of which 69 percent were confined to lymph nodes. [J Urol 2020;204:1222-1228]

The rate of metastasis-free survival was lower in men with GG2 compared to those with GG1 disease. A higher risk of metastases were predicted by GG2 (hazard ratio [HR], 19.8, 95 percent confidence interval [CI], 4.9–79.3; p<0.01), PSA velocity (HR, 1.4, 95 percent CI, 1.1–1.7; p=0.01), and PI-RADS 4-5 lesions on multiparametric MRI (HR, 8.5, 95 percent CI, 2.2–33.1; p=0.01).

The low metastasis rate in men with GG1 disease is in line with those reported from previous studies with large cohort managed with surgery. [J Urol 2011;185:869-875; Am J Surg Pathol 2012;36:1346-1352]

Notably, the 7-year prostate cancer-specific survival was >99 percent.

“The incidence of metastases and prostate cancer-specific mortality are consistent with prior studies on the long-term oncologic safety of AS,” the researchers said. “To date, results from a number of AS cohorts have been limited to a median follow-up of 5 years, with only a few studies assessing outcomes beyond 10 years.” [J Clin Oncol 2015;33:272-277; Eur Urol Oncol 2019;2:483-489]

Furthermore, tissue-based genetic assays have been recommended to improve AS selection criteria. A study by Cullen and colleagues found that genomic prostate score (GPS) independently correlated with risk of adverse pathology and biochemical recurrence, as well as with metastatic progression on multivariable analysis. [Eur Urol 2015;68:123-131]

“In our cohort GPS was not associated with a higher likelihood of metastatic progression, possibly as a result of the relatively low number of metastatic cases,” the researchers said.

Several studies have also shown the capacity of multiparametric MRI in predicting upgrade during surveillance, but there remains no consensus on its clinical application in AS. [Prostate Cancer Prostatic Dis 2019;22:5-15;Eur Urol 2020;77:675-682]

“On multivariable analysis, we found that having a PI-RADS 4-5 lesion was associated with a higher risk of metastases compared to not undergoing  multiparametric MRI, suggesting that incorporating [this] into AS protocols may provide further information for the management of patients on AS,” the researchers said.