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Background: Since its initial description the prostate biopsy technique for detection of prostate cancer (PCA) has constantly evolved. Multiparametric magnetic resonance imaging (mpMRI) has been proven to have a sensitivity exceeding 90% to detect the index lesion. This narrative review discusses the evidence around several biopsy strategies, especially in the context of patients that might be eligible for focal therapy. Method: A non-systematic literature research was performed on February 15th 2024 using the Medical Literature Analysis and Retrieval System Online (Medline), Web of Science and Google Scholar. Results: The transrectal (TR) route is associated with an increased postoperative sepsis rate, even with adequate antibiotic prophylaxis. The transperineal (TP) route is now recommended by international guidelines, firstly for its decreased rate of urosepsis. Recent evidence shows a non-inferiority of TP compared to TR route, and even a higher detection rate of clinically significant PCA (csPCA) in the anterior and apical region, that are usually difficult to target using the TR route. Several targeting techniques (cognitive, software-fusion or in-bore) enhance our ability to provide an accurate risk assessment of prostate cancer aggressiveness and burden, while reducing the number of cores and reducing the number of clinically insignificant prostate cancer (ciPCA). While MRI-TB have proven their role, the role of systematic biopsies (SB) is still important because it detects 5–16% of csPCA that would have been missed by MRI-TB alone. The strategies of SB depend mainly on the route used (TR vs. TP) and the number of cores to be collected (10–12 cores vs. saturation biopsies vs. trans-perineal template mapping-biopsies or Ginsburg Protocol vs. regional biopsies). Conclusion: Several biopsy strategies have been described and should be known when assessing patients for focal therapy. Because MRI systematically under evaluates the lesion size, systematic biopsies, and especially perilesional biopsies, can help to increase sensitivity at the cost of an increased number of cores.

Background: The IP1-PROSTAGRAM study showed that a short, non-contrast MRI detected more significant cancers with similar rates of biopsy compared to PSA. Herein, we compare the expected and perceived burden of PSA, MRI and ultrasound as screening tests. Methods: IP1-PROSTAGRAM was a prospective, population-based, paired screening study of 408 men conducted at seven UK primary care practices and two imaging centres. The screening tests were serum PSA, non-contrast MRI and ultrasound. If any test was screen-positive, a prostate biopsy was performed. Participants completed an Expected Burden Questionnaire (EBQ) and Perceived Burden Questionnaire (PBQ) before and after each screening test. Results: The overall level of burden for MRI and PSA was minimal. Few men reported high levels of anxiety, burden, embarrassment or pain following either MRI or PSA. Participants indicated an overall preference for MRI after completing all screening tests. Of 408 participants, 194 (47.5%) had no preference, 106 (26.0%) preferred MRI and 79 (19.4%) preferred PSA. This indicates that prior to screening, participants preferred MRI compared to PSA (+6.6%, 95% CI 4.4–8.4, p= 0.02) and after completing screening, the preference for MRI was higher (+21.1%, 95% CI 14.9–27.1, p< 0.001). The proportion of participants who strongly agreed with repeating the test was 50.5% for ultrasound, 65% for MRI and 68% for PSA. A larger proportion of participants found ultrasound anxiety-inducing, burdensome, embarrassing and painful compared to both MRI and PSA. Conclusions: Prostagram MRI and PSA are both acceptable as screening tests among men aged 50–69 years. Both tests were associated with minimal amounts of anxiety, burden, embarrassment and pain. The majority of participants preferred MRI over PSA and ultrasound. Registration: This study was registered on clinicaltrials.gov at https://clinicaltrials.gov/ct2/show/NCT03702439.

Background: For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies. Methods: Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28–83) and 62 (42–83) months, respectively. Results: At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9–87.3) than after focal therapy (72.8%, 95% CI 66.8–79.8) although not statistically significant (p= 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1–95.2 versus 97.5%, 95% CI 94–99.9; p= 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p< 0.001), but EBRT patients had a higher risk of mortality than focal patients (p= 0.008). Conclusions: Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.

Introduction: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). Methods: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason </= 4 + 3 and stage </= T2c were 1–1 propensity score-matched for treatment year, age, PSA, Gleason, T-stage, cancer core length and use of neoadjuvant hormones. FT included 1–2 sessions. Primary outcome was failure-free survival (FFS) defined by need for salvage local or systemic therapy or metastases. Differences in FFS were determined using Kaplan–Meier analysis with log-rank test. Results: 335 radical prostatectomy and 501 focal therapy patients were eligible for matching. For focal therapy, 420 had HIFU and 81 cryotherapy. Cryotherapy was used predominantly for anterior cancer. After matching, 246 RP and 246 FT cases were identified. For radical prostatectomy, mean (SD) age was 63.4 (5.6) years, median (IQR) PSA 7.9 g/ml (6–10) and median (IQR) follow-up 64 (30–89) months. For focal therapy, these were 63.3 (6.9) years, 7.9 ng/ml (5.5–10.6) and 49 [34–67] months, respectively. At 3, 5 and 8 years, FFS (95%CI) was 86% (81–91%), 82% (77–88%) and 79% (73–86%) for radical prostatectomy compared to 91% (87–95%), 86% (81–92%) and 83% (76–90%) following focal therapy (p= 0.12). Conclusions: In patients with non-metastatic low- intermediate prostate cancer, oncological outcomes over 8 years were similar between focal therapy and radical prostatectomy.

IMPORTANCE: Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations. OBJECTIVE: To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019. INTERVENTIONS: All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion–targeted biopsies were performed if the MRI or ultrasonography results were positive. MAIN OUTCOMES AND MEASURES: The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher. RESULTS: A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases. CONCLUSIONS AND RELEVANCE: In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.

Despite advances in robotic-assisted surgery (RAS) in the past two decades, control of the robotic system currently remains under the command of a human surgeon. Historically, urology has pioneered new surgical techniques and technologies. Now, autonomous RAS is on the horizon and the first data from clinical trials of autonomous RAS in urology are being published. Automation takes control away from the surgeon but promises standardization of techniques, increased efficiency, potentially reduced complication rates and new ways of integrating intra-operative imaging. Preclinical and clinical evidence is emerging that supports the use of autonomous robotic-assisted urological surgery. Use of autonomous technologies in the operating theatre will directly affect the role of the urological surgeon. Integration of autonomous RAS can be viewed as a positive aid, but it might also be perceived as a threat to the future urological surgeon.

Metastasis-directed therapy (MDT) in the form of stereotactic ablative radiation therapy (SABR), or in combination with surgical metastasectomy, may have a role in cancer control and disease progression.

In the past decade rigorous debate has taken place about population-based screening for prostate cancer. Although screening by serum PSA levels can reduce prostate cancer-specific mortality, it is unclear whether the benefits outweigh the risks of false-positive results and overdiagnosis of insignificant prostate cancer, and it is not recommended for population-based screening. MRI screening for prostate cancer has the potential to be analogous to mammography for breast cancer or low-dose CT for lung cancer. A number of potential barriers and technical challenges need to be overcome in order to implement such a programme. We discuss different approaches to MRI screening that could address these challenges, including abbreviated MRI protocols, targeted MRI screening, longer rescreening intervals and a multi-modal screening pathway. These approaches need further investigation, and we propose a phased stepwise research framework to ensure proper evaluation of the use of a fast MRI examination as a screening test for prostate cancer.

Prostate biopsy guided by magnetic resonance imaging (MRI) is increasingly used to obtain tissue from men with suspected prostate cancer (PC).

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.

In the past decade, a revolution in the treatment of metastatic prostate cancer has occurred with the advent of novel hormonal agents and life-prolonging chemotherapy regimens in combination with standard androgen-deprivation therapy. Notwithstanding, the use of systemic therapy alone can result in a castrate-resistant state; therefore, increasing focus is being placed on the additional survival benefits that could potentially be achieved with local cytoreductive and/or metastasis-directed therapies. Local treatment of the primary tumour with the established modalities of radiotherapy and radical prostatectomy has been explored in this context, and the use of novel minimally invasive ablative therapies has been proposed. In addition, evidence of the potential clinical benefits of metastasis-directed therapy with ionizing radiation (primarily stereotactic ablative radiotherapy) is accumulating. Herein, we summarize the pathobiological rationale for local cytoreduction and the potentially systemic immunological responses to radiotherapy and ablative therapies in patients with metastatic prostate cancer. We also discuss the current evidence base for a cytoreductive strategy, including metastasis-directed therapy, in the current era of sequential multimodal therapy incorporating novel treatments. Finally, we outline further research questions relating to this complex and evolving treatment landscape.

This is the first study, to the authors’ knowledge, to report that patients are willing to accept additional cytoreductive treatments to the prostate and metastases for progression-free and survival benefits. We report willingness to accept 10 percentage-point increases in urinary incontinence and fatigue to gain 3.4 and 2.7 mo of post-treatment survival time, respectively. These results can be used to support policy on the commissioning and delivery of current, and emerging, cytoreductive treatments for newly diagnosed metastatic prostate cancer.

The intracellular volume fraction derived from Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT) MRI enables better differentiation of a Gleason 4 lesion from benign and/or Gleason grade 3+3 lesions in prostate cancer with a high level of repeatability and similar image quality compared with apparent diffusion coefficient values.

Background:: Men with negative prostate biopsies or those diagnosed with low-risk or low-volume intermediate-risk prostate cancers often require a second prostate biopsy prior to a treatment decision. Prostate HistoScanning (PHS) is an ultrasound imaging test that might inform prostate biopsy in such men. Methods:: PICTURE was a prospective, paired-cohort validating trial to assess the diagnostic accuracy of imaging in men requiring a further biopsy (clinicaltrials.gov, NCT01492270) (11 January 2012–29 January 2014). We enrolled 330 men who had undergone a prior TRUS biopsy but where diagnostic uncertainty remained. All eligible men underwent PHS and transperineal template prostate mapping (TTPM) biopsy (reference standard). Men were blinded to the imaging results until after undergoing TTPM biopsies. We primarily assessed the ability of PHS to rule out clinically significant prostate (negative predictive value [NPV] and sensitivity) for a target histological condition of Gleason =4+3 and/or a cancer core length (MCCL) =6?mm. We also assessed the role of visually estimated PHS-targeted biopsies. Results:: Of the 330 men enrolled, 249 underwent both PHS and TTPM biopsy. Mean (SD) age was 62 (7) years, median (IQR) PSA 6.8 (4.98–9.50)?ng/ml, median (IQR) number of previous biopsies 1 (1–2) and mean (SD) gland size 37 (15.5)?ml. One hundred and forty six (59%) had no clinically significant cancer. PHS classified 174 (70%) as suspicious. Sensitivity was 70.3% (95% CI 59.8–79.5) and NPV 41.3% (95% CI 27.0–56.8). Specificity and positive predictive value (PPV) were 14.7% (95% CI 9.1–22.0) and 36.8% (95% CI 29.6–44.4), respectively. In all, 213/220 had PHS suspicious areas targeted with targeting sensitivity 13.6% (95% CI 7.3–22.6), specificity 97.6% (95% CI 93.1–99.5), NPV 61.6% (95% CI 54.5–68.4) and PPV 80.0% (95% CI 51.9–95.7). Conclusions:: PHS is not a useful test in men seeking risk stratification following initial prostate biopsy.

Prostate cancer lesions smaller than 0.5 m3, or Gleason pattern 3, are likely clinically insignificant. Clinically significant disease is often limited to a single index lesion. Focal ablation targets this index lesion, maintains oncological control, and minimizes complications by preserving healthy prostate tissue. Template mapping biopsy or multiparametric MRI-targeted biopsies are used to identify appropriate index lesions. Multiple energy modalities have been tested, including high-intensity frequency ultrasound, cryoablation, laser ablation, photodynamic therapy, focal brachytherapy, radiofrequency ablation, irreversible electroporation. Outcome is assessed by biopsy of the target area, triggered by prostate-specific antigen measurements or MRI imaging, or performed per protocol at 12 months.

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.

Evaluating a number of different pathways from the IP1-PROSTAGRAM study, using combinations of a short magnetic resonance imaging scan (PROSTAGRAM) and prostate-specific antigen (PSA), we found that a pathway starting with a PSA level of ≥1 ng/ml followed by a community-based PROSTAGRAM scan was the preferred screening strategy warranting further evaluation.

Nature Reviews Clinical Oncology 11, 482–491 (2014) In the published version of this article, the affiliation and position held by Dr Viktor Berge was incorrectly stated as Professor of Urology and Director of Research at the University Hospital Oslo. Dr Berge is a Consultant Urologist at the Department of Urology, at the Oslo University Hospital.

In this analysis, there was an incremental relationship between prostate cancer burden and the likelihood of a positive MRI signal.

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted.

Findings of research using modern multiparametric MRI have provided clinicians with reliable targets for guiding prostate biopsy sampling and directing targeted therapy, often termed focal therapy, to specific areas of the prostate. This emerging shift in treatment strategy from a whole-gland approach to a lesion-specific or region-specific approach requires novel medical devices. The rules regulating the approval and clinical use of such new devices often differ between the USA and Europe, and these differences can affect the treatments that patients receive. Current regulatory pathways for approval of various image-guided biopsy and focal therapy devices intended to be used in patients with prostate cancer are discussed in detail. Finally, we offer some perspective on the current status of research in the field, and propose a potential roadmap towards the establishment of timely, safe and standardized criteria for optimal evaluation of novel image-guided devices for treatment of patients with localized prostate cancer.

The aim of this study was to demonstrate the feasibility of the recently introduced Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumours (VERDICT) framework for imaging prostate cancer with diffusion-weighted magnetic resonance imaging (DW-MRI) within a clinical setting.

Focal therapy aims to reduce side-effects of active whole-gland therapies with an acceptable or noninferior oncologic benefit for the patient. The definition of the lesion to treat using this tissue-preserving approach is central, and there is a recent shift in considering more aggressive disease than in the past. This article examines recent consensus reports, assessment of emerging techniques, histologic considerations as well as results of trials and their development.

Tissue-preserving focal therapies that target individual cancer lesions rather than the whole prostate have emerged as potential interventions for localized prostate cancer. In this article, the Prostate Cancer RCT Consensus Group recommends the development of a cohort-embedded randomized controlled trial methodology to evaluate focal therapy use in men with clinically significant localized disease. The importance for a randomized controlled trial design to provide cost-efficient practice-changing data is highlighted.

Focal therapy for localised prostate cancer requires accurate disease localization and characterization. Standard trans-rectal ultrasound biopsy can miss significant cancer and cannot accurately localize prostate cancer to guide focal therapy. This article examines various biopsy and imaging strategies to determine which is the most useful in diagnosing prostate cancer suitable for treatment with focal therapy.

There has been a growing interest in focal treatment for prostate cancer, although this remains a controversial area. Criticism of focal prostate therapy has been based on the fact that prostate cancer is a multifocal disease. The authors of this Review discuss the clinical and biological implications of multifocal prostate cancer in the context of focal therapy patient selection and treatment planning.

The use of MRI for the management of prostate cancer is controversial; however, technological advances in the past few years indicate that this diagnostic approach should be utilized. The authors propose MRI could improve risk stratification not only for those diagnosed with prostate cancer but in men prior to a biopsy. They explain how MRI evaluation could help select those men who require intervention and avoid biopsy and unnecessary treatment in others.

The use of lasers to carry out resection of the prostate gland is an ever-evolving field which has seen several different modalities of laser light used with varying success. This review looks at what makes the traditional transurethral resection of prostate the gold standard and provides the evidence on the evolution of the laser prostatectomy in trying to usurp it as the favored procedure for symptomatic benign prostatic hyperplasia. In particular, we show how the latest laser technology in the form of the Greenlight laser is challenging not only other lasers such as the holmium laser, but may form a strong contender to replace the transurethral resection of prostate.