Health-related quality of life in Japanese low-risk prostate cancer patients choosing active surveillance: 3-year follow-up from PRIAS-JAPAN

Purpose: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN). Methods: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS. Results: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS. Conclusion: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy. Study registration: Clinical trial registry—UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11

The efficacy and toxicity of cabazitaxel for treatment of docetaxel-resistant prostate cancer correlating with the initial doses in Japanese patients

Background: We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC). Methods: We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated. Results: PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9–4.4), 2.1 months (1.2–5.5), and 3.0 months (2.0–4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7–30.9), 30.9 months (11.8–47.4), and 10.2 months (8.6–20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin < 12 g/dl (P = 0.030), and low initial CBZ dose (P = 0.030). Grade 4 neutropenia occurred in 53 patients (45%) and was associated with a low CBZ dose (hazard ratio 0.21, 95% CI 0.08–0.59, P = 0.002). Conclusions: CBZ at a higher initial dose may have similar response rate and response duration, but longer survival duration after treatment with higher toxicity than a lower initial dose for docetaxel-resistant CRPC in Japanese patients

Personalised biopsy schedules based on risk of Gleason upgrading for patients with low-risk prostate cancer on active surveillance

Objective: To develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted risks to create risk-based personalised biopsy schedules as an alternative to one-size-fits-all schedules (e.g. annually)

Reasons for Discontinuing Active Surveillance: Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium

BackgroundCareful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa).ObjectiveUsing Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation.Design, setting, and participantsWe compared data from 10296 men on AS from 21 centres across 12 countries.Outcome measurements and statistical analysisCumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation.Results and limitationsDuring 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for &gt;5yr, 4561 had follow-up for &lt;5yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4-28.6%) at 5yr and 38.2% (95% CI: 36.7-39.9%) at 10yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up.ConclusionsOur descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression.Patient summaryOur assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS

Prostate Cancer Patients Under Active Surveillance with a Suspicious Magnetic Resonance Imaging Finding Are at Increased Risk of Needing Treatment: Results of the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium

BackgroundThe inclusion criterion for active surveillance (AS) is low- or intermediate-risk prostate cancer. The predictive value of the presence of a suspicious lesion at magnetic resonance imaging (MRI) at the time of inclusion is insufficiently known.ObjectiveTo evaluate the percentage of patients needing active treatment stratified by the presence or absence of a suspicious lesion at baseline MRI.Design setting and participantsA retrospective analysis of the data from the multicentric AS GAP3 Consortium database was conducted. The inclusion criteria were men with grade group (GG) 1 or GG 2 prostate cancer combined with prostate-specific antigen &lt;20 ng/ml. We selected a subgroup of patients who had MRI at baseline and for whom MRI results and targeted biopsies were used for AS eligibility. Suspicious MRI was defined as an MRI lesion with Prostate Imaging Reporting and Data System (PI-RADS)/Likert ≥3 and for which targeted biopsies did not exclude the patient for AS.Outcome measurements and statistical analysisThe primary outcome was treatment free survival (FS). The secondary outcomes were histological GG progression FS and continuation of AS (discontinuation FS).Results and limitationsThe study cohort included 2119 patients (1035 men with nonsuspicious MRI and 1084 with suspicious MRI) with a median follow-up of 23 (12-43) mo. For the whole cohort, 3-yr treatment FS was 71% (95% confidence interval [CI]: 69-74). For nonsuspicious MRI and suspicious MRI groups, 3-yr treatment FS rates were, respectively, 80% (95% CI: 77-83) and 63% (95% CI: 59-66). Active treatment (hazard ratio [HR] = 2.0, p &lt; 0.001), grade progression (HR = 1.9, p &lt; 0.001), and discontinuation of AS (HR = 1.7, p &lt; 0.001) were significantly higher in the suspicious MRI group than in the nonsuspicious MRI group.ConclusionsThe risks of switching to treatment, histological progression, and AS discontinuation are higher in cases of suspicious MRI at inclusion.Patient summaryAmong men with low- or intermediate-risk prostate cancer who choose active surveillance, those with suspicious magnetic resonance imaging (MRI) at the time of inclusion in active surveillance are more likely to show switch to treatment than men with nonsuspicious MRI