Editing Prostate Cancer: Diagnosis and evaluation (section)

====== Targeted biopsy only vs. targeted and systematic ======
* '''<span style="color:#ff00ff">MRI-FIRST (2019)</span>'''
** Objective: determine whether biopsy of MRI detected lesions increases detection of clinically significant prostate cancer compared to standard biopsy i.e. can we omit standard biopsy and do only targeted biopsy?
** '''Design: paired-diagnostic study (non-randomized)'''
**'''Population: 275 patients with clinical suspicion of prostate cancer'''
** '''Intervention: MRI followed by standard systematic biopsy then targeted biopsy of up to 2 lesions on MRI. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only.'''
** '''Primary outcome: detection of clinically significant prostate cancer'''
** '''Results:'''
*** '''No difference in detection of clinically significant prostate cancer''' (30% systematic biopsy vs. 32% targeted biopsy)
*** Clinically significant prostate cancer would have been missed in 5% of patients had systematic biopsy not been done, and in 8% of patients had targeted biopsy not been done
** '''Obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer compared to systematic biopsy alone but does not seem to avoid the need for systematic biopsy'''
** '''</span>'''[https://pubmed.ncbi.nlm.nih.gov/30470502/ Rouvière, Olivier, et al.] "Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study." The Lancet Oncology 20.1 (2019): 100-109.
*'''<span style="color:#ff00ff">Ahdoot et al. (2020)</span>'''
**Study design: cohort study
**Population: 2103 males with an elevated PSA or abnormal DRE with a positive MRI underwent a targeted and systematic biopsy
**Outcomes:
***Primary outcomes: cancer detection rates by grade group for each biopsy method
**Results
***Use of MRI-targeted biopsy led to more diagnoses of cancers in grade groups 3, 4, and 5 than systematic biopsy and fewer cancers in grade group 1
***The addition of MRI-targeted biopsy to systematic biopsy led to 208 (9.9%) more prostate cancer diagnoses. Of these new diagnoses, 59 (28.4%) were clinically significant (grade group ≥3) disease.
***MRI-targeted biopsy was responsible for upgrading of events in 458 patients (21.8%) when added to systematic biopsy
***MRI-targeted biopsy alone without systematic biopsy would have led to no detection of cancers of grade group 2 or higher in 123 patients (5.8%) and no detection of cancers of grade group 3 or higher in 41 patients (1.9%)
***Among the patients who underwent radical prostatectomy, upgrading on histopathological analysis after undergoing combined biopsy occurred 14% of patients. The rates of any upgrading or clinically significant upgrading on whole-mount histopathological analysis were substantially higher for systematic biopsy and MRI-targeted biopsy (30.9% and 8.7%, respectively) than for combined biopsy
**Authors' interpretation: Among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy.
**[https://pubmed.ncbi.nlm.nih.gov/32130814/ Ahdoot, Michael, et al.] "MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis." ''New England Journal of Medicine'' 382.10 (2020): 917-928.
*'''<span style="color:#ff00ff">GOTEBORG-2 (2022/2024)</span>'''
**Objective: Determine whether targeted-biopsy only (and avoid systematic) is adequate in patients with elevated PSA (3-10 ng/ml) and prostate MRI
**Population: Swedish males aged 50-60 living in Gothenburg, Sweden, without previous diagnosis of prostate cancer
**Randomized to invited screening with PSA test vs. no invitation
***If PSA > 3 ng/mL, patients underwent prostate MRI
****Further randomized to
*****Reference group: Systematic (regardless of MRI results) +/- targeted biopsy if MRI positive (PR3-5) vs.
*****Experimental group: Targeted biopsy only if MRI positive (PR3-5) (experimental group); If PSA>10, patients underwent systematic biopsy, with or without targeted biopsy, regardless of MRI results
******If low-grade prostate cancer (mainly with Gleason 3+3 cancer but also some with Gleason 3+4 cancer) detected by targeted biopsy in the experimental group, were invited to undergo follow-up systematic biopsy. The Gleason score was thus based on both targeted and systematic biopsies after a cancer diagnosis in both groups in order to avoid sampling bias due to different primary biopsy techniques. 
**Outcomes:
***Primary outcome: detection of clinically insignificant prostate cancer, defined as a Gleason score of 3+3.
***Secondary outcome: detection of clinically significant prostate cancer, defined as a Gleason score of 3+4 or higher
**Results:
***19,733 (52%) of those randomized to invitation to screening underwent PSA testing
****1371 (7%) had PSA > 3 ng/mL
*****95% of patients with PSA > 3 ng/mL underwent MRI
***Risk of clinically insignificant prostate cancer at screening or at interval: significantly more common in patients undergoing systematic +/- targeted biopsy compared to targeted biopsy only (2.4% vs. 1.0%)
***Risk of clinically significant prostate cancer at screening or at interval: no significant difference (2.1% systematic +/- targeted vs. 1.8% targeted biopsy only)
***(2022 publication) 10 patients in reference group found to have clinically significant prostate cancer on systematic only
****9 with negative MRI, 1 with false-positive MRI
*****All GG2, GG4 <5% in 6 patients
******6 managed with AS
***(2022 publication) 128 patients in experimental group with PSA <10 diagnosed with cancer by targeted biopsy only
****72/128 (56%) had GG1
*****86% underwent systematic biopsy
*****26% upgraded (all GG2 except 1 to 3+5)
****Gleason 3+3 lesions that had been detected by systematic biopsy differed only in tumor extension from those that had been detected by targeted biopsy of suspicious lesions shown on MRI, with greater volume measured in tumors that were visible on MRI
**Author's interpretation: 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.
**[https://pubmed.ncbi.nlm.nih.gov/39321360/ Hugosson, Jonas, et al.] "Results after Four Years of Screening for Prostate Cancer with PSA and MRI." ''New England Journal of Medicine'' 391.12 (2024): 1083-1095.
**[https://pubmed.ncbi.nlm.nih.gov/36477032/ Hugosson, Jonas, et al.] "Prostate cancer screening with PSA and MRI followed by targeted biopsy only." ''New England Journal of Medicine'' 387.23 (2022): 2126-2137.