Long-term Study Stresses Importance of Active Surveillance in Low-risk Prostate Cancer

September 9, 2015

Article

A paper published in the Journal of Clinical Oncology, authored by Tosoian et al, reports on the long-term outcomes of prospective active surveillance (AS) of patients with favorable-risk prostate cancer.

Journal of Clinical Oncology, authored by Tosoian et al, reports on the long-term outcomes of prospective active surveillance (AS) of patients with favorable-risk prostate cancer.¹

The authors point out that the common widespread practice of screening for prostate cancer in the United States, using prostate-specific antigen (PSA), may have led to overdiagnosis and overtreatment of the disease.

The US Preventive Services Task Force has issued a grade D recommendation to reduce the use of PSA screening, and the National Institutes of Health has made a study of the outcomes of AS a research priority as well.^2,3

Study Design

This prospective study began in January 1995 and continued through to analysis in June 2014. It recruited 1298 men with very low-risk (VLR) prostate cancer.^4,5Study participants were monitored by AS, and curative intervention was given if disease advanced. This was triggered if biopsy findings no longer met inclusion criteria. Among the inclusion criteria for VLR were stage T1c disease, PSA density (PSAD) less than 0.15 ng/mL, biopsy Gleason score of ≤6, ≤2 positive biopsy cores, and cancer present in a maximum of 50% of the biopsy core. Patients with low-risk (LR) prostate cancer were also admitted to the study (stage ≤T2a, PSA <10 ng/mL, Gleason score ≤ 6).¹Assessments included in the protocol for surveillance are shown in Table 1.

Table 1. Protocol Assessments.¹

Table 1. Protocol Assessments.1

The majority of patients were white (88.4%), 7.4% were black, and the remainder consisted of other ethnicities. Median age at enrollment was 66 years (41-92 years). 926 men were admitted under VLR criteria and 372 under LR criteria. The median time of follow-up was 4.0 years (0.01-18.0 years) for individuals still at risk, and 5.0 years (0.01-18.0 years) for all patients at latest follow-up time from study entry. In total, a follow-up of ≥5 years was achieved for 650 patients and ≥10 years for 184 patients. At data cut-off in June 2014, 50% (642/1298) of patients were still in the study, and 36% (470/1298) were administered curative treatment. Another 14% (186/1298) were either undecided about treatment, lost to follow-up, withdrew, or died. The primary outcomes were overall survival (OS), cancer-specific survival and metastasis-free survival. Secondary outcomes included rates of biopsy reclassification and curative intervention. Incidence rates were expressed as per 100 patient years.¹

Findings

The primary outcome survival rates are shown in Figure 1.¹

Figure 1. Primary outcome survival rate.¹

Figure 1. Primary outcome survival rate.1

Secondary outcomes

The cumulative incidences of grade reclassification and curative treatment were 26% and 31% and 50% and 57% at 10 and 15 years respectively. The median treatment-free survival time was 8.5 years (0.01-18 years). Grade reclassification was associated with older age, an increase in PSAD, and a greater number of biopsy cores. An increase in PSAD and greater number of biopsy cores were also associated with treatment intervention.¹

Forty-nine (4%) patients died during follow-up. The most common overall cause of death was cardiovascular disease, and the median age at death was 75.5 years (59.2-90.6 years). Two patient deaths (0.15%) were attributed to prostate cancer. Patients who died, but not from prostate cancer, had received AS for a median of 7.0 years (1.0- 18.0 years).¹

Given the importance of cancer grade with regard to survival, the study examined the reclassification rates for patients who were VLR versus LR. At 5, 10, and 15 years, rates were 13%, 21%, 22% and 19%, 28%, and 31%, respectively.¹

In addition, biochemical recurrence (BCR), (defined as a PSA level ≥0.2 in patients who received surgery or ≥2.0 ng/mL in excess of the nadir in men who had radiation therapy) was determined for patients who received treatment. The findings revealed that among these 287 patients who had long enough follow-up, 23 had BCR, 8% had surgical intervention, and 8% had radiation therapy. The authors concluded by stating, “survival that was free of BCR was not significantly different on the basis of treatment modality (P= .90).”¹

To Surveil or Not to Surveil?

The authors concede that there is substantial evidence to support the fact that early detection and treatment can benefit some patients with particular tumor characteristics. Tosoian et al also noted that overtreatment of low-risk disease, especially in elderly patients, may not improve outcomes. They recommended that a more widespread adoption of AS may depend on changing physician practice patterns. Physicians will need to build confidence that a nonlethal phenotype is being monitored and improve explanations of cancer risk to patients, according to the study authors.¹

The present study shows that in low-risk patients, following diagnosis, the risk of progression to a dangerous phenotype is low for a median of 10 years. Summing up the message from their study, the authors state, “Our data suggest that, for men with favorable-risk prostate cancer, the paradigm of immediate intervention must be replaced by one of immediate contemplation and a thoughtful assessment of prognostic risk, life expectancy, and the relative risks and benefits of available management options considered in the context of personal preferences.”¹

References

1. Tosoian JJ, Mamawala M, Epstein JI, et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer.J Clin Oncol. pii:JCO.2015.62.5764.

2. Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement.Ann Intern Med.2012;157:120-134.

3. Ganz PA, Barry JM, Burke W, et al. National Institutes of Health State-of-the-Science Conference: role of active surveillance in the management of men with localized prostate cancer.Ann Intern Med. 2012;156:591-595.

4. Epstein JI, Walsh PC, Carmichael M, et al. Pathologic and clinical

findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer.

JAMA. 1994;271:368-374.

5. Carroll PR, Parsons JK, Andriole G, et al. Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines.J Natl Compr Canc Netw. 2014;12:1211-1219.