Omitting Biopsy After Negative MRI Halves Diagnoses of Insignificant Prostate Cancer

Omitting systematic biopsy in men with elevated prostate-specific antigen (PSA) levels and negative MRI results, and performing only targeted biopsy of MRI-positive lesions, eliminated more than half of diagnoses of clinically insignificant prostate cancer, according to results from a 4-year follow-up of the randomized GÖTEBORG-2 screening trial.

In the intention-to-treat analysis, the risk of detecting clinically insignificant cancer, either by screening or as interval cancer, was 57% lower in the MRI-targeted biopsy group than in the systematic biopsy group (relative risk 0.43, 95% CI 0.32-0.57, P<0.001), reported Jonas Hugosson, MD, PhD, of Sahlgrenska University Hospital in Gothenburg, and colleagues.

That relative risk was even lower at repeat rounds of screening compared with the first round (relative risk 0.25 vs 0.49), they wrote in the New England Journal of Medicine.

“Omitting prostate biopsy in men with negative MRI results, and thereby delaying a potential cancer diagnosis, was associated with a substantial reduction in the detection of clinically insignificant cancer and a very low risk of detecting incurable cancers at repeat screening rounds or as interval cancers,” Hugosson and team noted.

The relative risk of having clinically significant cancer detected either by screening or as interval cancer in the MRI-targeted biopsy group compared with the systematic biopsy group was 0.84 (95% CI 0.66-1.07). The number of advanced or high-risk cancers detected (by screening or as interval cancer) was 15 in the MRI-targeted biopsy group and 23 in the systematic biopsy group (relative risk 0.65, 95% CI 0.34-1.24).

“The largest advantage of switching to MRI-targeted biopsy only is that it decreases diagnoses of clinically insignificant cancers,” Hugosson and colleagues wrote. “Diagnosis of a cancer that should be treated is delayed in some instances, but more often, diagnosis of a cancer that is not likely to ever lead to symptoms and that otherwise could have led to years of unnecessary active surveillance, the risk of unnecessary treatment, and the stigma of a cancer diagnosis is prevented.”

They noted that there were just five cases of very-high-risk or advanced metastatic cancer in the MRI-targeted biopsy group and seven in the systematic biopsy group that were detected at rescreening or as an interval cancer. Thus, the data “strongly indicate that most prostate cancers become visible on MRI before they become incurable,” they pointed out.

A total of 42 interval cancers were detected during follow-up — 17 in the MRI-targeted biopsy group and 25 in the systematic biopsy group. Of the interval cancers that were detected, six in the MRI-targeted biopsy group and 15 in the systematic biopsy group were clinically significant.

In an editorial accompanying the study, Paul F. Pinsky, PhD, of the National Cancer Institute, noted that performing an MRI on all men with an elevated PSA level is a “resource-intensive strategy,” but the approach used in this study helped mitigate that issue by minimizing the number and extent of biopsies.

This study “contributes to the ultimate goal of designing screening strategies that preserve most of the benefits of PSA-based screening while reducing harms and costs,” he wrote.

Hugosson and colleagues agreed that their approach initially could be “resource consuming” as centers build up MRI capacity.

“However, because MRI decreases the need for prostate biopsy and the associated risk of infectious complications by more than 50% and, even more importantly, helps avoid unnecessary cancer diagnoses, these resources seem well spent,” they added.

In this updated analysis of the GÖTEBORG-2 trial, 13,153 men ages 50 to 60 were randomly assigned to either systematic biopsy or MRI-targeted biopsy. Those in the systematic biopsy group underwent MRI-targeted biopsy if suspicious lesions were found. They were invited to repeat screening 2, 4, or 8 years later, depending on PSA level.

The primary outcome was detection of clinically insignificant (International Society of Urological Pathology [ISUP] grade 1) prostate cancer, and detection of clinically significant (ISUP grade ≥2) cancer was a secondary outcome. Detection of clinically advanced or high-risk (metastatic or ISUP grade 4 or 5) cancer was also assessed. Median follow-up was 3.9 years, and median age at first PSA measurement was 56.

Five men had severe adverse events that led to hospitalization (three in the systematic biopsy group and two in the MRI-targeted biopsy group), with four events likely to have been related to the biopsy procedure.