Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance

08 March 2023


Guan Hee Tan, Dominik Deniffel, Antonio Finelli, Marian Wettstein, Ardalan Ahmad, Alexandre Zlotta, Neil Fleshner, Robert Hamilton, Girish Kulkarni, Gregory Nason, Khaled Ajib, Jaime Herrera-Caceres, Thenappan Chandrasekar, Nathan Perlis                                                                


Abstract

Purpose

To validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS).

Methods

We evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS.

Results

During median follow-up of 7.8 years, (IQR 7.3–8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%–81%) vs. 89% (95% CI: 83%–96%) in men with high (≥0.06 ml−1) vs. low (<0.06 ml−1) TCLo density, and 63% (95% CI: 48%–82%) vs. 90% (95% CI: 83%–96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml−1 increase]: 1.18, 95% CI: 1.05–1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20–2.38, P = 0.002) were associated with shorter PFS.

Conclusion

The previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml−1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.


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Cite

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance,
Urologic Oncology: Seminars and Original Investigations,
Volume 41, Issue 3,
2023,
Pages 146.e23-146.e28,
ISSN 1078-1439,
https://doi.org/10.1016/j.urolonc.2022.12.003.
(https://www.sciencedirect.com/science/article/pii/S1078143922004884)

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