1: Short-term hormone therapy associated with radiotherapy as salvage treatment after radical prostatectomy: results of the GETUG-AFU 16 phase III randomized trial

Results of the GETUG-AF 16 randomised multicentre phase 3 trial were published in the Lancet this month. The trial investigated the addition of short-term androgen suppression to salvage radiotherapy (RT) on survival in men with rising PSA concentrations after radical prostatectomy.

Over 700 patients were enrolled in the study and randomly assigned to receive RT alone or RT plus goserelin. The average age of both groups was 67 years. All patients received 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT). Patients in the RT plus goserelin group were given goserelin acetate by subcutaneous injection on the first day of irradiation and again after 3 months. Primary endpoints were progression-free survival (clinical or biological progression, or both) and death from any cause.

At final analysis, follow-up was around 5 years. The authors reported no additional serious acute or late genitourinary, gastrointestinal, or cardiovascular toxicities in the RT plus goserelin group. 5-year progression-free survival in the radiotherapy plus goserelin group was significantly higher than in the radiotherapy alone group (80% vs. 62%, respectively). The median duration to relapse was significantly different between the two groups (22 months in the radiotherapy alone group vs. 32 months in the RT plus goserelin group). The results showed no significant differences in health-related quality of life between the two groups. The authors acknowledged the need for longer follow-up, in order to establish the effect of this therapeutic strategy on overall survival, and suggested that combined RT and goserelin treatment could delay the need for more aggressive therapy.

2. Systematic review and meta-analysis indirectly comparing abiraterone acetate and enzalutamide for the treatment of metastatic CRPC

This literature‑based systematic review and meta‑analysis evaluated the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration‑resistant prostate cancer (mCRPC).

AA and Enz are two new agents that block androgen synthesis. Recent studies have demonstrated that tumour progression after androgen deprivation therapy commonly remains hormone driven, thus, therapies targeting residual androgen production may be promising and well‑tolerated alternatives to standard chemotherapy. In this study a literature search of the PubMed, Embase, and Web of Science databases in 2015 to identify relevant studies was carried out. Using the defined search criteria analysis of ten manuscripts on phase III trials for the indirect comparisons between AA and Enz as treatments for mCRPC, and 8 case series studies and 1 case–control study were used to evaluate the optimal sequencing of AA and Enz.

The authors reported results of indirect comparisons from their analysis and review demonstrated improvement in overall survival (OS) was not significantly different between AA and Enz. However, they reported the results suggested a potential advantage of Enz over AA in most secondary endpoints, including time to PSA progression, radiographic progression free survival (PFS), PSA response rate, time to health-related quality of life (HRQoL) deterioration, and time to initiation of chemotherapy (chemotherapy‑naive patients). However, the authors also highlighted that their review had not shown any head‑to‑head comparison. They acknowledged several limitations of the study, particularly the differences in baseline characteristics among the trials – including the inclusion of patients with visceral disease in some (but not all) of the trials and the inclusion of case series studies for evaluating optimal sequencing, which have relatively low methodological quality.

In conclusion it was reported that AA and Enz demonstrated similar survival benefits in patients with mCRPC before and after chemotherapy, whilst Enz may be advantageous for secondary endpoints including time to PSA progression, radiographic PFS, PSA response rate, time to HRQoL deterioration, and time to initiation of chemotherapy (chemotherapy‑naive patients).

3. The role of targeted biopsy in active surveillance

Prostate-specific antigen (PSA) testing is associated with higher prevalence of favourable-risk prostate cancer. Active surveillance (AS) can reduce over-treatment of men with favourable disease. Advances in multiparametric magnetic resonance imaging (mpMRI) allow high-quality visualization of the prostate and improved identification of prostate cancer. Some studies have shown that mpMRI/TRUS fusion biopsy (targeted biopsy) is associated with greater detection of high-risk cancer and lower detection of low-risk cancer when compared to SB. The authors of this study sought to assess the use of targeted biopsy among active surveillance candidates.

In this study retrospective evaluation of 12-core transrectal ultrasound-guided prostate biopsy (TRUS biopsy) and targeted biopsy among 230 men was conducted (103 AS men undergoing surveillance biopsy, 54 men undergoing confirmatory biopsy (CB), and 73 men referred for diagnostic biopsy (DB; comparison group)). The mpMRI protocol was performed using a 3.0-T whole body scanner, and T2-weighted imaging, diffusion weighted imaging and dynamic contrast enhanced imaging were interpreted by a radiologist. PI-RADS version 2 was used to score regions of interest, and scores ≥3 were considered positive and targeted on biopsy.

Gleason score (GS) ≥7 was detected by either of the two biopsy methods in 24% of men in the AS group, 22% in the CB group, and 75% in the DB group. GS ≥7 was found in 24.3% by SB + TB versus 20.4% by SB in the AS group (p = 0.13); in 22.2% by SB + TB versus 16.7% by SB in the CB group (p = 0.25); and in 75.3% by SB + TB versus 58.9% by SB in the DB group (p = 0.002).

The sensitivity for GS ≥7 detection was lower for TB than for SB (p = 0.006) in the AS cohort (relative sensitivity ratio 0.33, 95% confidence interval 0.16–0.71). Higher PI-RADS score (4 vs 3, odds ratio [OR] 2.00, p = 0.04; 5 vs 3, OR 4.74, p = 0.02), lower MRI-estimated prostate volume (OR 1.20 per 10-cm3 lower volume, p = 0.01), larger ROI (OR 1.04 per mm, p = 0.02), and right-sided ROI (OR 2.27, p = 0.01) were associated with finding cancer on TB. A potential limitation is that not all men who presented for biopsy underwent targeted biopsy and the urologist was not blinded to MRI results before TRUS biopsy.

In summary the authors indicated that image-guided prostate biopsy alone may not be informative for men enrolled in an active surveillance program for prostate cancer, and TRUS biopsy should still be performed on this group.

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