Accuracy of Transperineal Targeted Prostate Biopsies, Visual Estimation and Image Fusion in Men Needing Repeat Biopsy in the PICTURE Trial

PURPOSE: To evaluate detection of clinically significant prostate cancer (csPCa) using MRI-targeted biopsies, and compare visual-estimation to image-fusion targeting, in patients requiring repeat prostate biopsies. MATERIALS AND METHODS: Prospective, ethics-committee approved, registered PICTURE trial enrolling 249 consecutive patients (11th/January/2012-29th/January/2014). Men underwent an mpMRI and were blinded to its results. All underwent transperineal template prostate mapping (TTPM) biopsies. In 200 with a lesion, this was preceded by visual-estimation and image-fusion targeted biopsies. For the primary endpoint, csPCa was defined as Gleason >/=4+3 and/or any grade of cancer length >/=6mm. Other definitions of csPCa were also evaluated. RESULTS: Mean (SD) age was 62.6 (7) years, median (IQR) PSA 7.17ng/ml (5.25, 10.09), mean primary lesion size 0.37cc (SD1.52), with mean 4.3 (SD2.3) targeted cores per lesion (visual-estimation and image-fusion combined) and mean 48.7 (SD12.3) TTPM-biopsy cores. TTPM-biopsies detected 97 (48.5%) cases of csPCa and 85 (42.5%) insignificant cancers. Overall, mpMRI-targeted biopsies detected 81 (40.5%) csPCa and 63 (31.5%) insignificant cancers. Eighteen (9%) with csPCa on MRI-targeted biopsies were benign or clinically insignificant on TTPM-biopsy. Thirty-four (17%) had csPCa detected on TTPM-biopsy but not on MRI-targeted biopsies; approximately half of these were present in non-targeted areas. csPCa was found with visual-estimation and image-fusion in 53/169 (31.3%) and 48/169 (28.4%) (McNemar's test, p=0.5322). Visual-estimation missed 23 (13.6%) csPCa detected by image-fusion; image-fusion missed 18 (10.8%) csPCa that visual-estimation detected. CONCLUSIONS: MRI-targeted biopsies are accurate at detection of csPCa and reducing over-diagnosis of insignificant cancers. To maximise detection both visual-estimation and image-fusion targeted biopsies are required

Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy

Background: Men who fail external beam radiotherapy (EBRT) are usually placed on delayed hormone therapy. Some of these men have localised recurrence that might be suitable for further local therapy. We aimed to describe patterns of recurrence, and suitability for focal ablative therapy, in those undergoing transperineal template prostate-mapping (TTPM) biopsies. / Method: 145 consecutive patients (December 2007-May 2014) referred with suspicion of recurrence due to rising PSA after EBRT or brachytherapy who underwent TTPM-biopsies. Suitability for focal ablative therapy required the cancer to be either unifocal or unilateral, or bilateral/multifocal with one dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3mm cancer core involvement. / Results: The mean age was 70.7 (SD 5.8) years. Median PSA at time of TTPM-biopsy was 4.5 (IQR 2.5–7.7). Overall, 75.9% (110/145) were suitable for a form of focal salvage treatment; 40.7% (59/145) were suitable for quadrant ablation, 14.5% (21/145) hemiablation, 14.5% (21/145) bilateral focal ablation and 6.2% (9/145) for index lesion ablation. / Conclusion: Three quarters of patients who have localised radio-recurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies

The FORECAST study - Focal recurrent assessment and salvage treatment for radiorecurrent prostate cancer.

BACKGROUND: One-third of men may experience biochemical failure by 8years following radical radiotherapy for localised prostate cancer. Over 90% of men are started on androgen deprivation therapy (ADT) which is non-curative and confers systemic side-effects. Focal salvage therapy (FST) limits collateral tissue damage and may improve therapeutic ratios. In order to deliver FST, distant disease must be ruled-out and intra-prostatic disease must be accurately detected, localised and characterised. AIM: FORECAST - Focal Recurrent Assessment and Salvage Treatment - is a study designed to evaluate a novel imaging-based diagnostic and therapeutic complex intervention pathway for men who fail radiotherapy. METHODS: Men with biochemical failure following radical prostate radiotherapy, prior to salvage therapy will be recruited. They will undergo whole-body multi-parametric MRI (WB-MRI), choline PET/CT, bone-scan and pelvic-mpMRI and then MRI transperineal-targeted biopsies (MRI-TB) and Transperineal Template Prostate Mapping Biopsy (TPM). Those suitable for FST will undergo either high intensity focused ultrasound (HIFU) or cryotherapy. RESULTS: Primary outcome measures: a) the accuracy of WB-MRI to detect distant metastatic disease; b) accuracy of prostate mpMRI in local detection of radiorecurrent prostate cancer; c) detection accuracy of MRI-TB; and d) rate of urinary incontinence following FST. CONCLUSION: Focal salvage therapy may confer lower rates of morbidity whilst retaining disease control. In order to deliver FST, intra- and extra-prostatic disease must be detected early and localised accurately. Novel diagnostic techniques including WB-MRI and MRI-TB may improve the detection of distant and local disease whilst reducing healthcare burdens compared with current imaging and biopsy strategies

Development and internal validation of prediction models for biochemical failure and composite failure after focal salvage high intensity focused ultrasound for local radiorecurrent prostate cancer: Presentation of risk scores for individual patient prognoses.

PURPOSE: Patient selection for focal salvage remains difficult. Therefore, we developed and internally validated prediction models for biochemical failure (BF) and a composite endpoint (CE) following focal salvage high intensity focused ultrasound (HIFU) for radiorecurrent prostate cancer. MATERIALS AND METHODS: A prospective HIFU registry identified 150 cases (November 2006-August 2015). Recurrence was assessed with multiparametric magnetic resonance imaging (MRI) combined with template prostate mapping biopsies, targeted biopsies, or systematic transrectal ultrasound-guided biopsies. Metastatic disease was ruled out with a positron emission tomography-computed tomography and a bone scan. Focal salvage HIFU consisted of quadrant-ablation, hemi-ablation, or index-lesion ablation. Cox-regression was used for BF (Phoenix-definition) and CE (BF/MRI+/biopsies+/local or systemic treatment/metastases+/prostate cancer specific mortality+). Internal validation was performed using bootstrap resampling (500 datasets) after which C-statistic and hazard ratios were adjusted. Models were calibrated and risk scores created. RESULTS: Median follow-up was 35 months (interquartile range: 22-52). Median biochemical disease-free survival (DFS) was 33 months (95% CI: 23-45). Median CE-free survival was 24 months (95% CI: 21-35). After multivariable analysis, DFS interval after primary radiotherapy, presalvage prostate-specific antigen (PSA), PSA-doubling time, prostatic volume, and T-stage (both MRI based) predicted BF. For the CE, PSA-doubling time was not predictive but additionally, primary Gleason score was. The adjusted C-statistics were 0.68 and 0.64 for BF and CE, respectively. Calibration was accurate until 48 months. The risk scores showed 3 groups, with biochemical DFS of 60%, 35%, and 7% and CE-free survival of 40%, 24%, and 0% at 4 years. CONCLUSION: Our model, once externally validated, could allow for better selection of patients for focal salvage HIFU