Summary Background Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, ...pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy. Methods We did this multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (template prostate mapping biopsy TPM-biopsy). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer. This study is registered on ClinicalTrials.gov , NCT01292291. Findings Between May 17, 2012, and November 9, 2015, we enrolled 740 men, 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88–96%) than TRUS-biopsy (48%, 42–55%; p<0·0001) and less specific (41%, 36–46% for MP-MRI vs 96%, 94–98% for TRUS-biopsy; p<0·0001). 44 (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis. Interpretation Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer. Funding PROMIS is funded by the UK Government Department of Health, National Institute of Health Research–Health Technology Assessment Programme, (Project number 09/22/67). This project is also supported and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre and is coordinated by the Medical Research Council Clinical Trials Unit (MRC CTU) at UCL. It is sponsored by University College London (UCL).
Following detection of high levels of serum prostate-specific antigen, many men are advised to have transrectal ultrasound-guided biopsy in an attempt to locate a cancer. This nontargeted approach ...lacks accuracy and carries a small risk of potentially life-threatening sepsis. Worse still, it can detect clinically insignificant cancer cells, which are unlikely to be the origin of advanced-stage disease. The detection of these indolent cancer cells has led to overdiagnosis, one of the major problems of contemporary medicine, whereby many men with clinically insignificant disease are advised to undergo unnecessary radical surgery or radiotherapy. Advances in imaging and biomarker discovery have led to a revolution in prostate cancer diagnosis, and nontargeted prostate biopsies should become obsolete. In this Perspective article, we describe the current diagnostic pathway for prostate cancer, which relies on nontargeted biopsies, and the problems linked to this pathway. We then discuss the utility of prebiopsy multiparametric MRI and novel tumour markers. Finally, we comment on how the incorporation of these advances into a new diagnostic pathway will affect the current risk-stratification system and explore future challenges.
Abstract Context Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening ...and treatment. Objective To perform a systematic review of complications from prostate biopsy. Evidence acquisition A literature search was performed using PubMed and Embase, supplemented with additional references. Articles were reviewed for data on the following complications: hematuria, rectal bleeding, hematospermia, infection, pain, lower urinary tract symptoms (LUTS), urinary retention, erectile dysfunction, and mortality. Evidence synthesis After biopsy, hematuria and hematospermia are common but typically mild and self-limiting. Severe rectal bleeding is uncommon. Despite antimicrobial prophylaxis, infectious complications are increasing over time and are the most common reason for hospitalization after biopsy. Pain may occur at several stages of prostate biopsy and can be mitigated by anesthetic agents and anxiety-reduction techniques. Up to 25% of men have transient LUTS after biopsy, and <2% have frank urinary retention, with slightly higher rates reported after transperineal template biopsy. Biopsy-related mortality is rare. Conclusions Preparation for biopsy should include antimicrobial prophylaxis and pain management. Prostate biopsy is frequently associated with minor bleeding and urinary symptoms that usually do not require intervention. Infectious complications can be serious, requiring prompt management and continued work into preventative strategies.
Abstract Context The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound–guided biopsy test that is blind to the location of the cancer. To increase the ...accuracy of this diagnostic pathway, a software-based magnetic resonance imaging–ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. Objective Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. Evidence acquisition We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Evidence synthesis Fourteen papers reporting the outcomes of 15 studies ( n = 2293; range: 13–582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2–50% vs 4.8–52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7–82.1% vs 14.3–59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5–16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). Conclusions Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. Patient summary We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.
Clinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects.
To report ...on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate.
This was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%).
Disease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies.
The primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality.
The median follow-up was 56 mo (interquartile range IQR 35–70). The median age was 65 yr (IQR 61–71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2–10.0). FFS was 99% (95% confidence interval CI 98–100%) at 1 yr, 92% (95% CI 90–95%) at 3 yr, and 88% (95% 85–91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97–99%), 100%, and 99% (95% CI 97–100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up.
Focal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects.
In this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.
Our study shows that at median follow-up of approximately 5 yr after focal high-intensity focused ultrasound, nine out of ten patients with predominantly intermediate- or high-risk prostate cancer are able to avoid surgery, radiotherapy, and systemic therapy. Prostate cancer–specific survival was 100%. There was a low probability of urinary incontinence (2%), erectile dysfunction (15%), and rectal side effects (rare).
Abstract Context Prostate biopsy (PB) represents the gold standard method to confirm the presence of cancer. In addition to traditional random or systematic approaches, a magnetic resonance imaging ...(MRI)–guided technique has been introduced recently. Objective To perform a systematic review of complications after transrectal ultrasound (TRUS)–guided, transperineal, and MRI-guided PB. Evidence acquisition We performed a systematic literature search of Web of Science, Embase, and Scopus databases up to October 2015, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Complications and mortality following random, systematic, and image-guided PBs were reviewed. Eighty-five references were included. Evidence synthesis The most frequent complication after PB was minor and self-limiting bleeding (hematuria and hematospermia), regardless of the biopsy approach. Occurrence of rectal bleeding was comparable for traditional TRUS-guided and image-guided PBs. Almost 25% of patients experienced lower urinary tract symptoms, but only a few had urinary retention, with higher rates after a transperineal approach. Temporary erectile dysfunction was not negligible, with a return to baseline after 1–6 mo. The incidence of infective complications is increasing, with higher rates among men with medical comorbidities and older age. Transperineal and in-bore MRI–targeted biopsy may reduce the risk of severe infectious complications. Mortality after PB is uncommon, regardless of biopsy technique. Conclusions Complications after PB are frequent but often self-limiting. The incidence of hospitalization due to severe infections is continuously increasing. The patient's general health status, risk factors, and likelihood of antimicrobial resistance should be carefully appraised before scheduling a PB. Patient summary We reviewed the variety and incidence of complications after prostate biopsy. Even if frequent, complications seldom represent a problem for the patient. The most troublesome complications are infections. To minimize this risk, the patient's medical condition should be carefully evaluated before biopsy.
ReIMAGINE represents the first efforts to define prostate cancer risk using the full spectrum of emerging diagnostics (both commercial and academic). The outputs will provide image-based data sets ...that will replace, or adjust, historical and flawed risk calculators.
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