Comparison of Multiparametric MRI-targeted and Systematic Biopsies for Detection of Cribriform and Intraductal Carcinoma Prostate Cancer.

Background Intraductal carcinoma (IDC) and invasive cribriform (Cr) subtypes of prostate cancer (PCa) are an indication of aggressiveness, but the evidence regarding whether MRI can be used to detect Cr/IDC-pattern PCa is contradictory. Purpose To compare the detection of Cr/IDC-pattern PCa at multiparametric MRI (mpMRI)-targeted biopsy versus systematic biopsy in biopsy-naive men at risk for PCa. Materials and Methods This study was a secondary analysis of a prospective randomized controlled trial that recruited participants with a clinical suspicion of PCa between April 2017 and November 2019 at five centers. Participants were randomized 1:1 to either the MRI arm or the systematic biopsy arm. Targeted biopsy was performed in participants with a Prostate Imaging Reporting and Data System score of at least 3. MRI features were recorded, and biopsy slides and prostatectomy specimens were reviewed for the presence or absence of Cr/IDC histologic patterns. Comparison of Cr/IDC patterns was performed using generalized linear mixed modeling. Results A total of 453 participants were enrolled, with 226 in the systematic biopsy arm (median age, 65 years [IQR, 59-70 years]; 196 biopsies available for assessment) and 227 in the mpMRI-targeted biopsy arm (median age, 67 years [IQR, 60-72 years]; 132 biopsies available for assessment). Identification of Cr/IDC PCa was lower in the systematic biopsy arm compared with the mpMRI arm (31 of 196 biopsies [16%] vs 33 of 132 biopsies [25%]; P = .01). No evidence of a difference in mean cancer core length (CCL) (11.3 mm ± 4.4 vs 9.7 mm ± 4.5; P = .09), apparent diffusion coefficient (685 µm2/sec ± 178 vs 746 µm2/sec ± 245; P = .52), or dynamic contrast-enhanced positivity (27 [82%] vs 37 [90%]; P = .33) for clinically significant PCa (csPCa) was observed between participants with or without Cr/IDC disease in the MRI arm. Cr/IDC-positive histologic patterns overall had a higher mean CCL compared with Cr/IDC-negative csPCa (11.1 mm ± 4.4 vs 9.2 mm ± 4.1; P = .009). Conclusion MRI-targeted biopsy showed increased detection of Cr/IDC histologic patterns compared with systematic biopsy. Clinical trial registration no. NCT02936258 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Scialpi and Martorana in this issue.

Magnetic Resonance Imaging-Targeted Versus Systematic Prostate Biopsies: 2-year Follow-up of a Prospective Randomized Trial (PRECISE).

BACKGROUND: The prospective randomized PRECISE trial demonstrated that magnetic resonance imaging (MRI) with only targeted biopsy (TBx) was noninferior to systematic transrectal ultrasound biopsy (SBx) in the detection of International Society of Urological Pathology grade group (GG) ≥2 prostate cancer (PC). An unanswered question is the outcome for patients who avoided a biopsy because of negative MRI findings. OBJECTIVE: To explore the rate of PC diagnosis based on 2-yr MRI for PRECISE participants who had no biopsy and for patients who had a negative result or GG 1 on TBx in comparison to those with a negative result or GG 1 on SBx. DESIGN, SETTING, AND PARTICIPANTS: The PRECISE prospective trial was conducted at five Canadian academic centers. The present analysis was for trial participants who were not diagnosed with clinically significant PC (csPC) at baseline. Of 453 randomized patients, 146 were diagnosed with GG ≥2 at baseline and were excluded. Eligible patients for this study included 83 men from the MRI arm who had negative MRI findings and no biopsy, 120 from the overall cohort who had a negative SBx or TBx, and 72 from the overall cohort who were diagnosed with GG 1 disease. INTERVENTION: MRI at 2 yr in all men in the MRI and SBx arms and TBx for lesions with a Prostate Imaging-Reporting and Data System score of ≥3 or on the basis of clinical suspicion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men diagnosed with GG ≥2 cancer. Secondary outcomes included the MRI outcome and the proportion of men diagnosed with GG 1 PC. RESULTS AND LIMITATIONS: Evaluable 2-yr MRI scans were available for 75 (56%) eligible patients in the MRI arm and 69 (49%) in the SBx arm. Of these patients, 55 (73%) in the MRI arm and 51 (67%) SBx arm had negative 2-yr MRI. Of the 76 patients in the SBx arm with 2-yr MRI, 16 (21%) had a biopsy, for which the result was negative in eight (10%), GG1 in two (2.6%), and GG ≥2 in six (7.9%) cases. Of the 75 men in the MRI arm with 2-yr MRI, eight (11%) were biopsied, for which the result was negative in four cases (5%) and GG ≥2 in the other four (5%). At 2 yr, including baseline biopsy results, 116/221 (52.5%) in the MRI arm and 113/204 (55%) in the SBx arm were free of GG ≥2 disease, treatment, death from any cause, or progression (OR 1.08; p = 0.66). CONCLUSIONS: After 2-yr follow-up including MRI for patients in both arms of PRECISE, there was no difference in the rate of csPC diagnosis between the MRI and SBx groups, even though 38% of men in the MRI group avoided an initial biopsy. PATIENT SUMMARY: The PRECISE trial compared systematic biopsy of the prostate to a strategy of magnetic resonance imaging (MRI) with targeted biopsy of any lesions suspicious for cancer on the scan. After 2 years of follow-up that included 2-year MRI with or without biopsy in both groups, there was no difference in the rate of diagnosis of significant cancer, even though 38% of men in the initial MRI arm avoided an initial biopsy, and 30% avoided biopsy altogether. The PRECISE trial is registered on ClinicalTrials.gov as NCT02936258.

Hospital encounters and associated costs of prostate evaluation for clinically important disease MRI vs. standard evaluation procedures (PRECISE) study from a provincial-payer perspective.

INTRODUCTION: Systematic transrectal ultrasonography (TRUS) biopsy has been the standard diagnostic tool for prostate cancer (PCa) but is subject to limitations, such as a high false-negative rate of cancer detection. Multiparametric magnetic resonance imaging (mpMRI) prior to biopsy is emerging as an alternative diagnostic procedure for PCa. The PRECISE study found that MRI followed by a targeted biopsy was more accurately able to identify clinically significant cancer than TRUS biopsy. METHODS: PRECISE study patients recruited in Ontario between January 2017 and November 2019 were linked to various Ontario provincial administrative databases available at the Institute for Clinical and Evaluative Sciences (ICES ) to determine health resources used, associated costs, and hospitalizations in the 14 days after biopsy. Costs are presented in 2021 CAD. RESULTS: A total of 281 males were included in this study, with 48.4% of the patients in the TRUS biopsy group, 28.1% in the MRI+, and 23.5% in the MRI- group. Twenty-one patients (15%) from the TRUS biopsy group were seen at a hospital in the 14 days after their biopsy compared to fewer than five patients (6%) from the MRI+ group. The mean per person per year (PPPY) costs for the TRUS and all MRI groups (MRI- and MRI+) were $7828 and $8525, respectively. CONCLUSIONS: Patients in the TRUS biopsy group experienced more hospital encounters compared to patients who received an MRI prior to their biopsy. This economic analysis suggests that MRI imaging prior to biopsy is not associated with a significant increase in costs.

Comparison of Multiparametric Magnetic Resonance Imaging-Targeted Biopsy With Systematic Transrectal Ultrasonography Biopsy for Biopsy-Naive Men at Risk for Prostate Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Magnetic resonance imaging (MRI) with targeted biopsy is an appealing alternative to systematic 12-core transrectal ultrasonography (TRUS) biopsy for prostate cancer diagnosis, but has yet to be widely adopted. Objective: To determine whether MRI with only targeted biopsy was noninferior to systematic TRUS biopsies in the detection of International Society of Urological Pathology grade group (GG) 2 or greater prostate cancer. Design, Setting, and Participants: This multicenter, prospective randomized clinical trial was conducted in 5 Canadian academic health sciences centers between January 2017 and November 2019, and data were analyzed between January and March 2020. Participants included biopsy-naive men with a clinical suspicion of prostate cancer who were advised to undergo a prostate biopsy. Clinical suspicion was defined as a 5% or greater chance of GG2 or greater prostate cancer using the Prostate Cancer Prevention Trial Risk Calculator, version 2. Additional criteria were serum prostate-specific antigen levels of 20 ng/mL or less (to convert to micrograms per liter, multiply by 1) and no contraindication to MRI. Interventions: Magnetic resonance imaging-targeted biopsy (MRI-TB) only if a lesion with a Prostate Imaging Reporting and Data System (PI-RADS), v 2.0, score of 3 or greater was identified vs 12-core systematic TRUS biopsy. Main Outcome and Measures: The proportion of men with a diagnosis of GG2 or greater cancer. Secondary outcomes included the proportion who received a diagnosis of GG1 prostate cancer; GG3 or greater cancer; no significant cancer but subsequent positive MRI results and/or GG2 or greater cancer detected on a repeated biopsy by 2 years; and adverse events. Results: The intention-to-treat population comprised 453 patients (367 [81.0%] White, 19 [4.2%] African Canadian, 32 [7.1%] Asian, and 10 [2.2%] Hispanic) who were randomized to undergo TRUS biopsy (226 [49.9%]) or MRI-TB (227 [51.1%]), of which 421 (93.0%) were evaluable per protocol. A lesion with a PI-RADS score of 3 or greater was detected in 138 of 221 men (62.4%) who underwent MRI, with 26 (12.1%), 82 (38.1%), and 30 (14.0%) having maximum PI-RADS scores of 3, 4, and 5, respectively. Eighty-three of 221 men who underwent MRI-TB (37%) had a negative MRI result and avoided biopsy. Cancers GG2 and greater were identified in 67 of 225 men (30%) who underwent TRUS biopsy vs 79 of 227 (35%) allocated to MRI-TB (absolute difference, 5%, 97.5% 1-sided CI, -3.4% to ∞; noninferiority margin, -5%). Adverse events were less common in the MRI-TB arm. Grade group 1 cancer detection was reduced by more than half in the MRI arm (from 22% to 10%; risk difference, -11.6%; 95% CI, -18.2% to -4.9%). Conclusions and Relevance: Magnetic resonance imaging followed by selected targeted biopsy is noninferior to initial systematic biopsy in men at risk for prostate cancer in detecting GG2 or greater cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT02936258.

Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up.

BACKGROUND: The initial report from the ASIST trial showed little benefit from targeted biopsy for men on active surveillance (AS) for prostate cancer. Data after 2-yr follow-up are now available for analysis. OBJECTIVE: To determine if there was a difference in the AS failure rate in a 2-yr follow-up period among men undergoing magnetic resonance imaging (MRI) before initial confirmatory biopsy (CBx) compared to those who did not. DESIGN, SETTING, AND PARTICIPANTS: This is the 2-yr post-CBx follow-up for the ASIST trial, a prospective, randomized, multicenter, open-label study for men with Gleason grade group (GG) 1 cancer eligible for AS. Patients were randomized to CBx with 12-core systematic sampling or MRI with systematic and targeted sampling. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients with GG ≤ 1 on CBx were followed for 2 yr and had MRI and biopsy at that time point. Patients failed AS if they were no longer under AS because of grade progression, clinical progression, subject choice, clinical judgment, treatment, or lost to follow-up. Clinically significant cancer (CSC) was defined as GG ≥ 2. RESULTS AND LIMITATIONS: In total, 259 men underwent CBx, 132 in the non-MRI and 127 in the MRI arm. After biopsy, 101 men in the non-MRI arm (76%) and 98 in the MRI arm (77%) continued AS. There were fewer men with AS failures in the MRI (19/98, 19%) compared to the non-MRI group (35/101, 35%; p =  0.017). At 2-yr biopsy there were fewer men with CSC in the MRI arm (9.9%, 8/81) than in the non-MRI arm (23%, 17/75; p =  0.048). Significant differences in AS failure rates were detected across the three centers in the MRI arm only (4.2% [2/48] vs 17% [4/24] vs 27% [7/26]; p =  0.019). CONCLUSIONS: Baseline MRI before CBx during AS results in 50% fewer AS failures and less grade progression over 2 yr. The center where MRI and targeted biopsy is performed may influence AS failure rates. PATIENT SUMMARY: The ASIST trial randomized 273 men on active surveillance with low-grade prostate cancer diagnosed within the last year to systematic biopsy or magnetic resonance imaging (MRI) with systematic and targeted biopsy. The initial report showed little benefit from targeted biopsy. However, after 2 yr of follow-up we found that baseline MRI before confirmatory biopsy resulted in 50% fewer failures of surveillance and less progression to higher-grade cancer. This confirms the value of MRI in men on surveillance. This study is registered at ClinicalTrials.gov (NCT01354171).

Active Surveillance Magnetic Resonance Imaging Study (ASIST): Results of a Randomized Multicenter Prospective Trial.

BACKGROUND AND OBJECTIVE: This study aimed to determine, in men recently diagnosed with grade group 1 (GG1) prostate cancer, if magnetic resonance imaging (MRI) with targeted biopsy could identify a greater proportion of men with GG ≥2 cancer on their confirmatory biopsy compared with systematic biopsies. The study was registered with www.clinicaltrials.gov (NCT01354171). DESIGN, SETTING, AND PARTICIPANTS: This study is a prospective, randomized, multicenter, open-label trial. Eligible patients were men diagnosed with GG1 cancer within 1 yr prior to study entry in whom a confirmatory biopsy was indicated. Patients were randomized to 12-core systematic biopsy or MRI with systematic and targeted biopsy using the Artemis fusion targeting system. The primary end point was the proportion upgraded to GG ≥2 in each arm. RESULTS AND LIMITATIONS: In total, 296 men were registered and 273 randomized. Of the MRI group, 64% had a region of interest. No difference was observed in the rate of GG ≥2 upgrading (the intent-to-treat population, p=0.7, and per-protocol [PP] population, p=0.4), GG ≥2 upgrading within each stratum separately, or GG ≥3. After central pathology review, upgrading was observed in 36/132 (27%) men in the systematic biopsy arm and 42/127 (33%) men in the MRI arm (p=0.3). Upgrading was seen in 19/137 (14%) patients in the MRI arm on targeted biopsy alone (median, 2 cores) compared with 31/136 (23%) in the systematic biopsy arm (median, 12 cores; p=0.09). In the MRI arm, 8/127 (6.5%) patients had GG ≥2 disease identified on targeted biopsy, but ≤GG1 on the systematic biopsy, and 10/127 (7.9%) patients had GG ≥2 disease identified by systematic biopsy but ≤GG1 on targeted biopsy. Significant differences in upgrading on targeted biopsies were seen between sites, likely reflecting different levels of expertise with the targeted biopsy technique. CONCLUSIONS: The addition of MRI with targeted biopsies to systematic biopsies did not significantly increase the upgrading rate compared with systematic biopsy alone. Furthermore, 2-core targeted biopsies alone resulted in a nonsignificant trend to less upgrading than 12-core systematic biopsy (p=0.09). In men on active surveillance, targeted biopsies identify most, but not all, clinically significant cancers.

A Phase II, Randomized, Multicenter Study Comparing 10 Months versus 4 Months of Degarelix Therapy in Prolonging the Off Treatment Interval in Men with Localized Prostate Cancer Receiving Intermittent Androgen Deprivation Therapy for Biochemical Recurrence following Radical Local Therapy.

PURPOSE: Clinical trials in men initiating intermittent androgen deprivation therapy have used a range of induction durations between 3 and 12 months. We sought to determine whether the duration of induction androgen deprivation therapy would influence the duration of the off treatment interval and the recovery of serum testosterone. MATERIALS AND METHODS: This was a prospective, randomized, open label study. Men with biochemical recurrence after local therapy for prostate cancer and a negative bone scan were randomized to 4 and 10 months of monthly degarelix. The first dose was 240 mg and subsequent doses were 80 mg per month. Quality of life was evaluated by the I-PSS (International Prostate Symptom Score), the PAS-SFI (Problem Assessment Scale of the Sexual Function Index) and the FACT-P (Functional Assessment of Cancer Therapy-Prostate). RESULTS: A total of 90 patients were randomized, including 43 to 4 months and 47 to 10 months of treatment. There was no difference in any relevant baseline laboratory parameter, including prostate specific antigen and testosterone. There was no difference between the 2 treatment groups in time off treatment (HR 1.51, 95% CI 0.60-3.84, p = 0.38). Actuarial median time to testosterone recovery to 8.0 nmol/l or greater was 8.05 months (95% CI 4.34-39.89) in the 10-month treatment arm and 6.24 months (95% CI 5.45-15.90) in the 4-month treatment arm. The log rank test showed no statistical significance between the 2 treatment groups in time to testosterone recovery (p = 0.8392). There was no difference in the testosterone recovery rate between the 2 arms. Men younger than 65 years had a considerably shorter interval off treatment and time to testosterone recovery. There was a lesser adverse effect on quality of life at the end of treatment in the 4-month than in the 10-month arm. CONCLUSIONS: In men with biochemical recurrence who initiated intermittent androgen deprivation therapy with degarelix no difference was observed in the duration of the off treatment interval or the rate of testosterone recovery whether they received 4 or 10 months of induction androgen deprivation therapy.

Effect of dutasteride in men receiving intermittent androgen ablation therapy: The AVIAS trial.

INTRODUCTON: We studied the effect of dutasteride on the length of the off-treatment period in prostate cancer patients on intermittent androgen deprivation (IAD) therapy. METHODS: We conducted a randomized, placebo-controlled Phase II trial in men with localized prostate cancer and a rising prostate-specific antigen (PSA) level post-primary treatment. Patients were randomized to dutasteride (0.5 mg/day) or placebo. All patients received androgen deprivation therapy (ADT), which was stopped at month 9 if the PSA level was <1.0 ng/mL. ADT was resumed when PSA increased to ≥5.0 ng/mL. End points included time off treatment, PSA nadir after 9 months of ADT, serum testosterone and dihydrotestosterone levels, and time to castrate-resistant prostate cancer (rising PSA while testosterone levels remain <50 ng/mL). RESULTS: There were 87 evaluable patients: 49 dutasteride, 38 placebo. In total, 80 patients completed one treatment cycle: 45 dutasteride, 35 placebo. The median time off treatment for patients reaching ≥5 ng/mL was 18.6 and 16.7 months for dutasteride and placebo, respectively (p = 0.7600). The median PSA nadir at 9 months was 0.1 and 0.075 ng/mL, respectively (p = 0.4486). There were no cases of androgen-independent prostate cancer. Our study limitations include its short duration with only one treatment cycle evaluated. CONCLUSIONS: This small-scale Phase II randomized controlled trial showed no benefit to the addition of dutasteride to an IAD regimen.

A phase 3, double-blind, randomised, parallel-group, placebo-controlled study of oral weekly alendronate for the prevention of androgen deprivation bone loss in nonmetastatic prostate cancer: the Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) study.

BACKGROUND: Androgen-deprivation therapy (ADT) induces loss of bone mineral density (BMD) and increases the risk of fractures in patients with prostate cancer (PCa). We sought to determine whether a weekly dose of alendronate, an oral bisphosphonate, could reduce this unwanted side-effect. OBJECTIVE: To assess whether once-weekly oral alendronate therapy would maintain or improve BMD in men initiating ADT for localised PCa. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, double-blind, randomised, placebo-controlled study, we included hormonally naïve PCa patients initiating ADT with leuprolide acetate 30 mg intramuscularly every 4 mo. INTERVENTION: Patients were randomised to receive either oral alendronate 70 mg once weekly or placebo for 1 yr. Both groups received daily calcium 1g and vitamin D 400 international units. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Changes in BMD (at the lumbar spine [LS] and total hip [TH]) and bone markers. RESULTS AND LIMITATIONS: One hundred ninety-one subjects were enrolled, and 186 were randomised between alendronate (n=84) and placebo (n=102). The alendronate group demonstrated a mean spine BMD increase of 1.7% compared with -1.9% in the placebo group (p<0.0001). Alendronate also increased the BMD at the hip (percent change: 0.7%) compared to placebo (-1.6%). Median urinary N-terminal crosslinking telopeptide of type I collagen (Ntx) values decreased by 3.5% in the alendronate group and increased by 16.5% in the placebo arm, even after adjusting for centre (p=0.510) and baseline urinary Ntx (p<0.0001). Bone-specific alkaline phosphatase (BSAP) decreased a median of 2.25% in the alendronate group and increased a median of 3.12% in the placebo arm, regardless of centre or baseline BSAP or other covariates (p<0.0001). The safety and tolerability profile was similar for the two treatment groups. CONCLUSIONS: Although the study was closed early because of slow accrual, it showed that weekly oral alendronate prevented bone loss and increased bone mass in addition to decreasing bone turnover in patients initiating ADT for localised PCa, with few related side-effects.