D.V. Matei

Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer

BACKGROUNDnThere is a need for active agents with a better safety profile than docetaxel, yet good activity, for patients with hormone-refractory prostate cancer (HRPC). We carried out a phase II trial to determine the activity and safety of estramustine plus oral etoposide in HRPC.nnnPATIENTS AND METHODSnPatients were given estramustine (280 mg twice daily) and etoposide (100 mg/day, days 1-21) in 28-day cycles until disease progression or unacceptable toxicity. Primary end points were overall response rate and safety, as determined by prostate-specific antigen (PSA) levels and lesion assessment.nnnRESULTSnFrom November 2001 to February 2007, 75 patients were enrolled. All patients were assessable for safety; 17 (22.6%) had grade 3/4 toxicity. PSA response was assessable in 69, 14 of whom had a >50% reduction in PSA. Of 10 patients with one or more measurable lesions, two (20%) had partial response and two (20%) disease stabilization. Overall, median time to progression was 4.4 months (range 1 week-43 months); median survival was 23 months (range 3 weeks-64+ months).nnnCONCLUSIONSnEstramustine plus etoposide is active and has a manageable safety profile in patients with HRPC. In asymptomatic patients with nonaggressive disease this combination could be useful to delay the start of more demanding treatments.

Multiparametric Magnetic-Resonance to Confirm Eligibility to an Active Surveillance Program for Low-Risk Prostate Cancer: Intermediate Time Results of a Third Referral High Volume Centre Active Surveillance Protocol

Background: To evaluate the role of confirmatory multiparametric magnetic resonance imaging (mpMRI) of the prostate at the time of Active Surveillance (AS) enrollment to reduce disease misclassification. Materials: From 2012 to 2016, 383 patients with low-risk disease respecting Prostate Cancer Research International AS criteria underwent confirmatory 1.5-T mpMRI. AS was proposed to patients with Prostate Imaging and Report and Data System (PI-RADS) score ≤3 and no extraprostatic extension (EPE), whereas patients with PI-RADS score ≥4 and/or EPE were treated actively. Kaplan-Meier analyses quantified progression-free survival (PFS) in patients enrolled in the AS program. Logistic regression analyses tested the association between confirmatory mpMRI and clinically significant prostate cancer (csPCa) at radical prostatectomy (RP). Diagnostic performance of mpMRI was calculated in patients submitted to immediate RP. Results: PFS rate was 99, 90 and 86% at 1, 2 and 3 years respectively. At multivariable analysis, PI-RADS 3, PI-RADS 4, PI-RADS 5 and EPE increased the probability of having csPCa at immediate RP (PI-RADS 3 [OR] 1.2, p = 0.26; PI-RADS 4 [OR] 5.1, p = 0.02; PI-RADS 5 [OR] 6.7; p = 0.009; EPE [OR] 11.8, p < 0.001). Confirmatory mpMRI showed sensibility, specificity, positive predictive value and negative predictive value of 85, 55, 68 and 76% respectively. Conclusions: MpMRI at the time of AS enrollment reduces the misclassification rate of csPCa. We suggest to perform target biopsies in patients with PI-RADS score 3 and 4 lesions.

Multiparametric-magnetic resonance imaging second opinion may reduce the number of unnecessary prostate biopsies. Time to improve radiologists’ training programme?

Purpose: To understand the multiparametric magnetic resonance imaging (mpMRI) interreader agreement between radiologists of peripheral and academic centers and the possibility to avoid prostate biopsies according to magnetic resonance imaging second opinion. Patients and Methods: This prospective observational study enrolled 266 patients submitted to mpMRI at nonacademic centers for cancer detection or at active surveillance begin. Images obtained were reviewed by 2 unblinded radiologists with 8 and 5 years’ experience on mpMRI, respectively. We recorded Prostate Imaging Reporting and Data System (PI‐RADS) v2 categories and management strategy changes after mpMRI rereadings. Interreader agreement was assessed by the Cohen kappa. For mpMRI second opinion, positive predictive value and negative predictive value were calculated. Results: In the original readings, no lesions (ie, PI‐RADS < 2) were observed in 17 cases (6.5%). Reported index lesion (IL) PI‐RADS category was 2 in 23 (8.5%), 3 in 85 (32%), 4 in 98 (37%), and 5 in 13 (5%) men, respectively. It is noteworthy that in 30 examinations (11%), an IL was recognized by radiologists, but a suspicious score was not assigned. According to first reading of mpMRI, initial clinical strategy included performing a targeted (226; 85%) or a systematic biopsy (8; 3%), scheduling the patient to an active surveillance program without repeat biopsy (10; 4%), or monitoring prostate‐specific antigen without prostate sampling (22; 8%). The mpMRI rereads did not change IL PI‐RADS category in 91 cases (38.5%), although in 20 (8.5%) and 125 (53%) IL PI‐RADS was upgraded or downgraded, respectively (&kgr; = 0.23). The clinical management changed in 113 patients (48%) (&kgr; = 0.2). Overall, 102 targeted biopsies (51%) were avoided and 72 men (34.5%) were not submitted to biopsy after mpMRI second opinion. Positive predictive value and negative predictive value of the mpMRI rereading were 58% and 91%, respectively. Major limitations of the study are limited‐time follow‐up and the lack of a standard of reference for some men, who were not submitted to biopsy according to mpMRI second opinion. Conclusion: There is an important level of discordance between mpMRI reports. According to imaging second opinion, roughly half of targeted biopsies could be avoidable and 34.5% of men could skipped prostate sampling. Prospective randomized trials are needed to confirm our findings. MICRO‐ABSTRACT In this prospective observational study, we observed a significant level of discordance between multiparametric magnetic resonance imaging of the prostate reports in peripheral and subspecialized centers. If confirmed by further prospective randomized trials, multiparametric magnetic resonance imaging second opinion by expert radiologists could become a useful tool to deliver the best management for patients, avoiding 52% of targeted and 33.5% of total biopsies.