Grade Inflation

This is the first research project from my PhD studies.

Preprint: DOI: 10.1101/2024.01.10.24300922
Published version: DOI: 0.1111/bju.70109

Abstract

Background:

The use of MRI-targeted biopsies has led to lower detection of Gleason Grade Group 1 (GG1) prostate cancer and increased detection of GG2 disease. Although this finding is generally attributed to improved sensitivity and specificity of MRI for aggressive cancer, it might also be explained by grade inflation.

Objective:

To determine the likelihood of definitive treatment and risk of post-treatment recurrence for patients with GG2 cancer diagnosed by targeted biopsies relative to men with GG1 cancer diagnosed with systematic biopsies.

Design and setting:

We performed a retrospective study using a large tertiary centre registry (HUS Academic Data Lake) to retrieve data on prostate cancer diagnostics, treatments, and cancer recurrence. We included patients with either GG1 diagnosed by systematic biopsies (3317 men) or GG2 diagnosed by targeted biopsies (554 men) from 1993 to 2019.

Outcome measurements and statistical analysis:

We assessed the risk of curative treatment and recurrence after treatment. Recurrence was defined as biochemical recurrence (prostate-specific antigen increase over 0.2 ng/ml after radical prostatectomy (RP) or 2 ng/ml over the nadir after radiation therapy) or secondary treatment. Kaplan-Meier survival curves were computed to assess treatment-free and recurrence-free survival. Cox proportional hazards regression was performed to assess the risk of post-treatment recurrence. Sankey diagrams were used to visualize treatment trajectories, and a series of sensitivity analyses was performed to assess the robustness of the conclusions.

Results and limitations:

Patients with GG1 cancer detected by systematic biopsy had a significantly longer median time to treatment (31 months) compared with patients with GG2 cancer detected by targeted biopsy (4 months, p < 0.0001). The risk of recurrence after curative treatment was similar between groups, with the upper bound of the 95% CI excluding an important difference (HR: 0.94, 95% CI [0.71-1.25], p=0.7). This was confirmed in sensitivity analyses of patients treated with RP only, patients treated within one year of diagnosis, those diagnosed with GG1 and never upgraded in subsequent biopsies, and models controlled for PSA and number of positive cores. Clinical indications for MRI and curative treatment are not known and changed alongside the Gleason grade definition during the study period, which represents a limitation.

Conclusions:

GG2 cancers detected by MRI-targeted biopsy are treated more aggressively than GG1 cancers detected by systematic biopsy despite having similar oncologic risk. To prevent further overtreatment related to the MRI pathway, treatment guidelines from the pre-MRI era need to be updated to account for changes in the diagnostic pathway.

Patient summary:

Prostate cancers diagnosed with MRI-targeted biopsies behave less aggressively than same-grade cancers diagnosed with systematic biopsies. Treatment guidelines need to be updated to prevent overtreatment.

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