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

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Transperineal Magnetic Resonance Imaging-targeted Biopsy versus Transperineal Template Prostate Mapping Biopsy in the Detection of Localised Radio-recurrent Prostate Cancer.

AIMS: Multi-parametric magnetic resonance imaging (mpMRI) may identify radio-recurrent intra-prostatic cancer accurately. We aimed to compare visually directed MRI-targeted biopsies (MRI-TB) to an accurate reference standard - transperineal prostate mapping (TPM) biopsies with 5 mm sampling - in the detection of clinically significant cancer in men with biochemical failure after radiotherapy. MATERIALS AND METHODS: A retrospective registry analysis between 2006 and 2014 identified 77 men who had undergone mpMRI followed by MRI-TB and TPM. Clinical significance was set at two definitions of disease. Definition 1 was Gleason ≥ 4+3 and/or maximum cancer core length ≥ 6 mm. Definition 2 was Gleason ≥ 3+4 and/or maximum cancer core length ≥ 4 mm. RESULTS: Of the 77 patients included, the mean age was 70 years (range 61-82; standard deviation 5.03). The median prostate-specific antigen (PSA) at the time of external beam radiotherapy (EBRT) was 14 ng/ml (interquartile range 7.83-32.50). The most frequent EBRT dose given was 74 Gy over 37 fractions. Eight patients had iodine-seed implant brachytherapy or high dose rate brachytherapy. Neoadjuvant/adjuvant hormonal therapy use was reported in 38. The time from EBRT to biochemical recurrence was a median of 60 months (interquartile range 36.75-85.00). The median PSA at the time of mpMRI was 4.68 ng/ml (interquartile range 2.68-7.60). The median time between mpMRI and biopsy was 2.76 months (interquartile range 1.58-4.34). In total, 2392 TPM and 381 MRI-TB cores were taken with 18% and 50% cancer detection, respectively. Detection rates of definition 1 clinically significant cancer were 52/77 (68%) versus 55/77 (71%) for MRI-TB and TPM, respectively. MRI-TB was more efficient requiring 1 core versus 2.8 cores to detect definition 2 cancer. CONCLUSION: MRI-TB seems to have encouraging detection rates for clinically significant cancer with fewer cores compared with TPM, although TPM had higher detection rates for smaller lower grade lesions.

MAPPED study design: a 6 month randomised controlled study to evaluate the effect of dutasteride on prostate cancer volume using magnetic resonance imaging.

OBJECTIVE: To evaluate the percentage change in volume of prostate cancer, as assessed by T2-weighted MRI, following exposure to dutasteride (Avodart) 0.5mg daily for six months. PATIENTS AND METHODS: MRI in Primary Prostate cancer after Exposure to Dutasteride (MAPPED) is a double-blind, placebo-controlled trial, supported by GlaxoSmithKline (GSK). Men with prostate cancer suitable for active surveillance (low-intermediate risk prostate cancer on biopsy), and a visible lesion on T2-weighted MRI of at least 0.2 cc, were eligible for consideration. Forty-two men were randomised to 6 months of daily dutasteride 0.5mg or placebo. Multi-parametric MRI (mpMRI) scans were performed at baseline, 3 and 6 months. The percentage changes in cancer volume over time will be compared between the dutasteride and placebo groups. Planned analyses will examine the association between tumour volume and characteristics (perfusion and contrast washout) as seen on mpMRI, HistoScan ultrasound and biopsy histopathology in both groups. DISCUSSION: MAPPED is the first randomised controlled trial to use mpMRI to look at the effect of dutasteride on the volume of prostate cancer. If dutasteride is shown to reduce the volume of prostate cancer, it might be considered as an adjunct for men on active surveillance. Analysis of the placebo arm will allow us to comment on the short-term natural variability of the MR appearance in men who are not receiving any treatment. CONCLUSION: MAPPED will evaluate the short-term effect of dutasteride on prostate cancer volume, as assessed by mpMRI, in men undergoing active surveillance for low or intermediate risk prostate cancer. The study completed recruitment in January 2012.

Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers.

Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant and benign tissues (p<0.001). Significantly increased expression of Ki-67 occurred in prostate cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in 67% of the sporadic controls (p>0.5). Similar results were obtained when the data were analysed using a threshold set at 3.5 and 7.1%. This study shows that elevated expression of Ki-67 is associated both with aggressive prostate cancers and with high Gleason score irrespective of whether their occurrence is against a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all prostate cancers occurring in the presence of BRCA germline mutations are clinically aggressive, their potentially different phenotypes consistently involve maximal rates of cell proliferation.

What the SHO really does.

BACKGROUND: Five years ago we described the acute caseload of a typical general medical senior house officer (SHO) post. This follow-up report assesses the effects of changes since then on SHOs' training. We also look at the opportunities for all medical SHOs to learn and practise the practical procedures suggested as being necessary during a six month unselected general medical take. RESULTS: In six months 752 patients presented, up by 29% in five years. They fell into 87 diagnostic categories. The ten most common categories accounted for 53% of cases seen, indicating little change over five years. The numbers of patients seen by the firm had increased from a mean of 14 to 20 on each take day, but with the appointment of a second SHO to the firm the numbers seen by each SHO fell to 10. Some techniques such as lumbar puncture were used frequently. Others listed as recommended training for all SHOs, such as vital capacity measurement, were not needed. Five procedures that our take patients did require, including Sengstaken tube insertion, are listed only under specialist training requirements. CONCLUSIONS: An SHO post in a DGH continues to offer good exposure to common medical problems but little to more rare conditions. The reduction in hours worked and other changes in the NHS have not altered this. Further thought may be required to formulate achievable recommendations for experience of practical procedures, or specific arrangements made for SHOs to be taught and allowed to practise those techniques for which there is little day-to-day patient need. Our findings support the recent changes to the Royal College of Physicians' requirements for general professional training and the use of log books to identify gaps in experience.