Percutaneous needle biopsy for indeterminate renal masses: a national survey of UK consultant urologists

<p>Abstract</p> <p>Background</p> <p>The use of percutaneous needle biopsy in the evaluation of indeterminate renal masses is controversial and its role in management remains largely unclear. We set to establish current practice on this issue in UK urology departments.</p> <p>Methods</p> <p>We conducted a national questionnaire survey of all consultant urologists in the UK, to establish current practice and attitudes towards percutaneous needle biopsy in the management of indeterminate renal masses.</p> <p>Results</p> <p>139 (43%) consultant urologists never use biopsy, whereas 111 (34%) always employ it for the diagnosis of indeterminate renal masses. 75 (23%) urologists use biopsy only for a selected patient group. Mass in a solitary kidney, bilateral renal masses and a past history of non-renal cancer were the main indications for use of percutaneous biopsy. The risk of false negative results and biopsy not changing the eventual management of their patients were the commonest reasons not to perform biopsy.</p> <p>Conclusion</p> <p>There is a wide and varied practice amongst UK Consultant Urologists in the use of percutaneous biopsy as part of the management of indeterminate renal masses. The majority of urologists believe biopsy confers no benefit. However there is a need to clarify this issue in the wake of recent published evidence as biopsy results may provide critical information for patients with renal masses in a significant majority. It not only differentiates benign from malignant tissue but can also help in deciding the management option for patients undergoing minimally invasive treatments.</p

Low temperature plasmas as emerging cancer therapeutics : the state of play and thoughts for the future

The field of plasma medicine has seen substantial advances over the last decade, with applications developed for bacterial sterilisation, wound healing and cancer treatment. Low temperature plasmas (LTPs) are particularly suited for medical purposes since they are operated in the laboratory at atmospheric pressure and room temperature, providing a rich source of reactive oxygen and nitrogen species (RONS). A great deal of research has been conducted into the role of reactive species in both the growth and treatment of cancer, where long-established radio- and chemo-therapies exploit their ability to induce potent cytopathic effects. In addition to producing a plethora of RONS, LTPs can also create strong electroporative fields. From an application perspective, it has been shown that LTPs can be applied precisely to a small target area. On this basis, LTPs have been proposed as a promising future strategy to accurately and effectively control and eradicate tumours. This review aims to evaluate the current state of the literature in the field of plasma oncology and highlight the potential for the use of LTPs in combination therapy. We also present novel data on the effect of LTPs on cancer stem cells, and speculatively outline how LTPs could circumvent treatment resistance encountered with existing therapeutics

The PICTURE study: diagnostic accuracy of multiparametric MRI in men requiring a repeat prostate biopsy.

BACKGROUND: Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy. METHODS: All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm. RESULTS: Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98-9.50), median (IQR) number of previous biopsies 1 (1-2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92-99), specificity 21.9% (15.5-29.5), negative predictive value (NPV) 91.4% (76.9-98.1) and positive predictive value (PPV) 46.7% (35.2-47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6-87.7), specificity 68.5% (60.3-75.9), NPV 83.3% (75.4-89.5) and PPV 64.3% (55.4-72.6). CONCLUSIONS: In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied

Focal HIFU therapy for anterior compared to posterior prostate cancer lesions.

OBJECTIVE To compare cancer control in anterior compared to posterior prostate cancer lesions treated with a focal HIFU therapy approach. MATERIALS AND METHODS In a prospectively maintained national database, 598 patients underwent focal HIFU (Sonablate®500) (March/2007-November/2016). Follow-up occurred with 3-monthly clinic visits and PSA testing in the first year with PSA, every 6-12 months with mpMRI with biopsy for MRI-suspicion of recurrence. Treatment failure was any secondary treatment (ADT/chemotherapy, cryotherapy, EBRT, RRP, or re-HIFU), tumour recurrence with Gleason ≥ 3 + 4 on prostate biopsy without further treatment or metastases/prostate cancer-related mortality. Cases with anterior cancer were compared to those with posterior disease. RESULTS 267 patients were analysed following eligibility criteria. 45 had an anterior focal-HIFU and 222 had a posterior focal-HIFU. Median age was 64 years and 66 years, respectively, with similar PSA level of 7.5 ng/ml and 6.92 ng/ml. 84% and 82%, respectively, had Gleason 3 + 4, 16% in both groups had Gleason 4 + 3, 0% and 2% had Gleason 4 + 4. Prostate volume was similar (33 ml vs. 36 ml, p = 0.315); median number of positive cores in biopsies was different in anterior and posterior tumours (7 vs. 5, p = 0.009), while medium cancer core length, and maximal cancer percentage of core were comparable. 17/45 (37.8%) anterior focal-HIFU patients compared to 45/222 (20.3%) posterior focal-HIFU patients required further treatment (p = 0.019). CONCLUSION Treating anterior prostate cancer lesions with focal HIFU may be less effective compared to posterior tumours

Comparative healthcare research outcomes of novel surgery in prostate cancer (IP4-CHRONOS): a prospective, multi-centre therapeutic phase II parallel randomised control trial

Introduction Focal therapy (FT) targets individual areas of cancer within the prostate, providing oncological control with minimal side-effects. Early evidence demonstrates encouraging short-medium-term outcomes. With no randomized controlled trials (RCT) comparing FT to radical therapies, Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (CHRONOS) will compare the cancer control of these two strategies. Patients and methods CHRONOS is a parallel phase II RCT for patients with clinically significant non-metastatic prostate cancer, dependent upon clinician/patient decision, patients will enrol into either CHRONOS-A or CHRONOS-B. CHRONOS-A will randomize patients to either radical treatment or FT. CHRONOS-B is a multi-arm, multistage RCT comparing focal therapy alone to FT with neoadjuvant agents that might improve the current focal therapy outcomes. An internal pilot will determine the feasibility of, and compliance to, randomization. The proposed definitive study plans to recruit and randomize 1190 patients into CHRONOS-A and 1260 patients into CHRONOS-B. Results Primary outcome in CHRONOS-A is progression-free survival (transition to salvage local or systemic therapy, development of metastases or prostate-cancer-related mortality) and in CHRONOS-B is failure-free survival (includes the above definition and recurrence of clinically significant prostate cancer after initial FT). Secondary outcomes include adverse events, health economics and functional outcomes measured using validated questionnaires. CHRONOS is powered to assess non-inferiority of FT compared to radical therapy in CHRONOS-A, and superiority of neoadjuvant agents with FT in CHRONOS-B. Conclusion CHRONOS will assess the oncological outcomes after FT compared to radical therapy and whether neoadjuvant treatments improve cancer control following one FT session

Evaluation of Outcomes following Focal Ablative Therapy for Treatment of Localised Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-year Experience

PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy (FT) in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: 649 patients across 11 UK sites receiving focal high intensity focused ultrasound (HIFU) or cryotherapy between June 2006 - July 2020 reported within the UK based HIFU Evaluation and Assessment of Treatment and the International Cryotherapy Evaluation (ICE) registries were evaluated. Primary outcome was failure free survival (FFS) defined by need for more than 1 focal re-ablation, progression onto radical treatment, development of metastases, need for systemic treatment or prostate cancer specific death. This was compared to the FFS in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). 60% had intermediate risk disease and 35% high risk disease. 113 patients (17%) required further treatment. 16 had radical treatment and 44 required systemic treatment. FFS was 82% (95% CI: 76-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year FFS was 96%, (95% CI: 93-100%) and 82% (95% CI: 75-91%) respectively, P < .001. 93% of those in the radical treatment arm had received Radiotherapy as their primary treatment with its associated use of Androgen Deprivation Therapy (ADT) thereby leading to potential over estimation of treatment success in the radical treatment arm, especially given the similar metastases free and overall survival rates seen. CONCLUSIONS: We propose FT to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment

Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer.

BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816

The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET):A Systematic Review and International Consensus Recommendations

Background and objective: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. Methods:A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. Key findings and limitations: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. Conclusions and clinical implications: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. Patient summary:Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.</p