Grade Inflation

This is my first research project during my PhD studies. Abstract is below, and full paper will be added later!

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 on a large tertiary centre registry (HUS Acamedic datalake) to retrieve data on prostate cancer diagnostics, treatments, and cancer recurrence. We included patients with either GG1 with systematic biopsies (3317 men) or GG2 with targeted biopsies (554 men) covering the years 1993 to 2019.

Outcome measurements and statistical analysis:

We assessed 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 a secondary treatment. Kaplan-Meier survival curves were computed to assess treatment- 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 series of sensitivity analyses were performed to assess the robustness of the conclusions.

Results and limitations:

Patients with systematic biopsy detected GG1 cancer have significantly longer median time-to-treatment (31 months) compared to patients with targeted biopsy detected GG2 cancer (4 months, p < 0,0001). 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 on sensitivity analysis on patients treated with RP only, patients treated within one year of diagnosis, those diagnosed with GG1 and never upgraded in subsequent biopsies and when controlled for PSA and number of positive cores. Clinical indication for MRI and curative treatment are not known and have changed along with Gleason grade definition during the study period and represent 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 take into account changes in the diagnostic pathway.

Patient summary:

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

If you have any feedback or comments, please feel free to leave them in the section below. Thank you!