MRI-Targeted and Systematic Biopsy Combo Enhances Diagnostic Accuracy in Prostate Cancer

Michael Ahdoot, MD, National Institutes of Health

Michael Ahdoot, MD

The combination of MRI-targeted and systemic biopsy led to increased detection of all prostate cancers in patients with MRI-visible lesions, according to results from a study published in the New England Journal of Medicine.¹

Additionally, results showed that the use of MRI-targeted biopsy alone resulted in an underestimation of the histologic grade of some tumors. Notably, following radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were reported to be significantly lower after combined biopsy.

In the study, a total of 2103 men underwent both biopsy methods. Cancer was diagnosed in 62.4% of patients (n = 1312) by combined biopsy and 19.2% of patients (n = 404) underwent radical prostatectomy. Additionally, cancer detection rates on MRI-targeted biopsy were significantly lower than on systemic biopsy for grade group 1 cancers and substantially higher for grade groups 3 through 5 (P <.01 for all comparisons).

Combined biopsy led to cancer diagnoses in 9.9% more men (n = 208) than with either method alone; it also led to 21.8% of men (n = 458) being upgraded to a higher-grade group. Investigators found that if only MRI-targeted biopsies had been performed, 8.8% of clinically significant cancers (grade group ≥3) would have been misclassified. Among those who underwent subsequent radical prostatectomy (n = 404), the combined biopsy method was associated with the fewest upgrades to grade group ≥3 on histopathological analysis of surgical specimens, at 3.5%, compared with MRI-targeted biopsy, at 8.7%, and systematic biopsy, at 16.8%.

"In this study, we found that combined biopsy leads to an increase in the number of cancer diagnoses and improves the likelihood that the biopsy findings are predictive of the true pathologic nature of the patient='s disease," wrote first author Michael Ahdoot, MD, of the National Institutes of Health, and co-investigators. "Patients who are found to have grade group 2 prostate cancer on combined biopsy have only a small chance of having clinically significant disease of grade group 3 or higher. This knowledge should reduce the risks of both overtreatment and undertreatment out of fear of misdiagnosis."

Investigators initiated the study to examine the use of electromagnetic tracking devices for MRI-targeted biopsies. Adult men who were ≥18 years of age and who had an elevated serum prostate-specific antigen level or an abnormal digital rectal examination were eligible to undergo prostate MRI. Those in whom a prostate lesion was detected on MRI and who consented to undergo a prostate biopsy were determined to be eligible for enrollment. Those who received previous treatment for prostate cancer, who had no MRI-visible prostate lesions, or who were unable to undergo MRI were excluded from the study.

All MRIs were reviewed by 1 of 2 expert genitourinary radiologists with more than a decade of experience in analyzing MRIs of the prostate. MRI lesions were assigned a Prostate Imaging Reporting and Data System score of 1 to 5 to identify the risk of prostate cancer; higher scores were indicative of more clinically suspicious lesions. Clinically insignificant disease was defined as grade group 1 (Gleason score, 3 + 3 = 6) and clinically significant cancer was defined as grade group 3 (Gleason score, 4 + 3 = 7; unfavorable intermediate risk). The detection of grade group 2 (Gleason score, 3 + 4 = 7; favorable intermediate risk) was also reported. “Some physicians consider this threshold to be more clinically relevant than grade group 3 or higher,” noted the study authors.

From June 2007 through January 2019, 2732 men underwent prostate MRI; 2180 were found to have MRI-visible lesions and underwent MRI-targeted and systematic biopsies in the same clinical setting. Seventy-seven patients who underwent biopsy were excluded from the analysis because they had previously undergone treatment. As such, a total of 2103 men were included in the analysis; in 1312 of these men (62.4%), prostate cancer was diagnosed. Following diagnosis, 404 men underwent radical prostatectomy.

Among all 2103 patients who underwent both biopsy methods, 52.5% (n = 1104) were diagnosed with prostate cancer by systematic biopsy alone, while 51.5% (n = 1084) were diagnosed with MRI-targeted biopsy alone. Notably, the use of MRI-targeted biopsy was found to result in more diagnoses of cancers in grade groups 3, 4, and 5 compared with systematic biopsy (P =.004, P <.001, and P =.003, respectively) and fewer cancers in grade group 1 (P <.001).

The addition of MRI-targeted biopsy to systematic biopsy led to 9.9% more prostate cancer diagnoses (n = 208). Of these new diagnoses, 28.4% (n = 59) were clinically significant, grade group ≥3 disease. The addition of MRI-targeted biopsy also led to a reduction of 60 patients who were classified as having clinically insignificant, or grade group 1 cancer (from 454 to 394). One-hundred and thirty-four men classified as grade group 1 who were diagnosed on systematic biopsy were upgraded to grade group ≥2 on MRI-targeted biopsy. Moreover, MRI-targeted biopsy also led to 74 new grade group 1 cancer diagnoses among men who originally had no detection of cancer with systematic biopsy. Cumulatively, 21.8% of patients who underwent the combined biopsy experienced an upgrading of events.

MRI-targeted biopsy alone detected clinically significant cancers (grade group ≥3) in 91.2% of patients (n = 466) whose cancer was detected by combination biopsy. However, MRI-targeted biopsy alone would not have led to the detection of cancers of grade group ≥2 in 5.8% of patients (n = 123); it would not have identified cancers of grade group ≥3 in 1.9% of patients (n = 41) either. Similarly, the exclusion of the systematic biopsy would not have resulted in the reclassification to higher-risk disease in 15.7% of patients (n = 330). A total of 8.3% of all patients who underwent biopsy were detected by MRI-targeted biopsy only and 1.9% of all patients who underwent biopsy were detected by systematic biopsy only (P <.001).

Approximately 14.4% of the 404 patients (n = 58) who underwent radical prostatectomy were upgraded on histopathological analysis after undergoing combined biopsy. Of these 58 patients, 3.5% (n = 14) of those who underwent radical prostatectomy were upgraded to clinically significant disease (grade group ≥3). The rates of any upgrading or clinically significant upgrading upon whole-mount histopathological analysis were substantially higher with systematic biopsy, at 41.6% and 16.8%, respectively, and MRI-targeted biopsy, at 30.9% and 8.7%, respectively, compared with the combined biopsy, which showed rates of 14.4% and 3.5%, respectively (P ≤.002 for all comparisons).

Downgrading to clinically insignificant cancer (grade group 1) upon histopathological analysis was uncommon, regardless of biopsy method, noted the investigators. However, downgrading was most common among patients who underwent combined biopsy (3.7%). The differences in downgrading to clinically insignificant disease between systematic biopsy and targeted biopsy were not determined to be statistically significant (2.2% and 2.5%, respectively; P =1.00).

"Among the patients in whom prostate cancer is diagnosed, the use of MRI-targeted biopsy alone leads to high diagnostic uncertainty, since this method used in isolation is associated with a 30.9% rate of any upgrading of the cancer group and an 8.7% rate of upgrading the cancer to a clinically significant grade group on whole-mount histopathological analysis," concluded the authors of the study. "Collectively, these findings suggest that combined biopsy provides improved diagnostic accuracy over either systemic or MRI-targeted biopsy alone and better predicts the results of final histopathological analysis."

Ahdoot M, Wilbur AR, Reese SE, et al. MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. N Eng J Med. 2020;382:917-928. doi:10.1056/NEJMoa1910038