Introduction:

Active surveillance (AS) is the preferred management in low and select intermediate risk prostate cancer patients. Currently, while the 4Kscore identifies men with grade group (GG) 2+ disease in men with clinical suspicion of prostate cancer, little is known about its utility in men undergoing AS, especially when incorporating MRI information. The MRI-Guided Active Selection for Treatment of Prostate Cancer (MAST) is a single-center, single-arm prospective study of men undergoing active surveillance for low to intermediate risk prostate cancer. In this study, we assessed the 4Kscore’s ability to predict tumor progression on active surveillance.

Methods:

We enrolled patients with biopsy-confirmed very low to intermediate risk prostate cancer who have elected for AS and obtained prostate MRI, targeted +/- systematic biopsy, and 4Kscore within 1 year of diagnosis and then yearly for 3 years. The 4Kscore was categorized as low (=<7%), intermediate (7%-19%), and high (=>20%) risk. The primary outcome was progression on study, defined as more than 4 cores with any grade cancer, more than 2 cores with GG3+4 cancer, any single core with GG4+3 or higher cancer, A GG3+3 at diagnosis upgraded to GG3+4, or any treatment regardless of histological progression. We estimated cumulative incidence rates of progression over time by the Kaplan-Meier method and used multivariable Cox analyses to assess the association between the 4Kscore and progression while adjusting for NCCN risk at diagnosis, age, and baseline PIRADS score.

Results:

The 4Kscore was collected in 166 men at the time of confirmatory biopsy. Over half the patients had a PIRADS4 or 5 lesions and 4K score of over 20% at baseline (Table 1). A total of 79 (47.6%) patients progressed during the study period, with 26.5%, 13.3%, 5.4%, and 2.4% progressing at the baseline, 12-month, 24-month, and 36-month visit, respectively. Patients who progressed had higher baseline 4Kscore compared with patients who did not progress (31% IQR 15-59 vs. 14% IQR 8-35, p<0.001; Figure 1a). Patients with a 4Kscore above 20% had higher cumulative incidence of progression by 36 months compared with patients with 4Kscores less than 20% (72.5% [95% CI 60.9-83.1%] vs. 41.0% [95% CI: 28.6-56.3%], p=0.0001, Figure 1b). In a multivariable Cox analysis, 4Kscore above 20% was an independent predictor of progression (HR 1.73, 95% CI: 1.03, 2.88, p=0.037), after adjusting for age, NCCN risk, and PIRADS score.

Conclusion:

This study demonstrated that patients with a 4Kscore above 20% have a higher likelihood of progression despite their NCCN risk and MRI findings. To our knowledge, this is the first study to prospectively evaluate the role of 4Kscore within an MRI based protocol. While further validation is needed, these results are promising and suggest the 4Kscore may be a useful tool for clinical decision making in AS.

Funding: NCI RO1CA189295, R01CA190105, U01CA239141, and Paps Corps Champions for Cancer Research Endowed Chair in Solid Tumor Research