Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsies for Prostate Cancer Diagnosis: Final Results of the Randomized PERFECT trial (CCAFU-PR1).

BACKGROUND: Recent guidelines favor transperineal (TP) prostate biopsies over the transrectal (TR) approach due to a reduced sepsis risk. Yet, evidence from controlled trial comparing both approaches within the MRI-targeted pathway for significant prostate cancer (PCa) detection is lacking. OBJECTIVE: To compare the significant PCa detection rate between magnetic resonance imaging (MRI)-targeted TR and TP approaches in biopsy-naïve patients. DESIGN, SETTING, AND PARTICIPANTS: In this noninferiority controlled trial, we randomized (ratio 1:1) 270 MRI-positive biopsy-naïve patients. INTERVENTION: MRI-targeted TP versus TR biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary outcome was the detection rate of significant PCa (International Society of Urological Pathology [ISUP] ≥2) in MRI-targeted biopsies. Secondary outcomes were any-grade PCa detection, detection on concomitant systematic biopsy, complications, and functional outcomes. RESULTS AND LIMITATIONS: Targeted biopsies identified significant PCa in 47.2% of TP and 54.2% of TR participants (-7%, p = 0.6235). On a per-lesion analysis, posterior lesions yielded higher detection rates via TR (59.0% vs 44.3%, p = 0.0443), while anterior lesions were more frequently detected via TP (40.6% vs 26.5%, p = 0.2228). The overall (any grade) cancer detection rate in targeted biopsies was comparable between groups: 71.3% (TP) versus 64.1% (TR; p = 0.2209) with significantly more ISUP 1 cases detected in the TP arm. Adverse events of grade ≥2 were not different between TP (35.7%) and TR (40.5%, p = 0.4256). One TR patient (0.8%) experienced grade 3 sepsis. Quality of life, and urinary and sexual function, as well as pain scores, were comparable between groups. CONCLUSIONS: Despite a comparable overall detection rate for any-grade PCa, noninferiority of TP over TR for MRI-targeted biopsies for significant PCa detection was not demonstrated. However, MRI lesion location influenced biopsy route performance, suggesting that a pragmatic approach based on lesion location might enhance significant PCa assessment. PATIENT SUMMARY: This trial compared the efficacy and safety of two biopsy approaches for prostate cancer diagnosis. Both approaches seem complementary according to the lesion location.

The Financial Burden of Guideline-recommended Cancer Medications for Metastatic Urothelial Carcinoma.

Bladder cancer is a significant global health concern owing to its prevalence, negative impact on quality of life, and high treatment costs. Treatment for metastatic urothelial carcinoma (mUC) traditionally relies on platinum-based chemotherapy regimens. However, clinical trial results have led to the approval of immune checkpoint inhibitors (ICIs) as viable treatment options. We assessed the escalating costs and economic viability of mUC treatment guidelines in Europe. We used a pragmatic approach that involved: (1) collection of the costs of the recommended medications in the five most populous European countries; (2) conversion of the costs into international dollars to account for differences in purchasing power parity among countries; (3) evaluation of the cost trends over time; and (4) comparison of the medication costs to World Health Organization thresholds. Introduction of ICIs in European guidelines substantially increased the cost of medications for mUC. Intriguingly, important differences across European countries emerged: the annual cost of medications was twofold higher in Italy than in France and the UK. Despite limitations, our study sheds light on the escalating costs and economic challenges of mUC treatment, and highlights the need for assessments of sustainable and cost-effective management approaches. PATIENT SUMMARY: We looked at the costs of treatments for metastatic bladder cancer and found that costs have been rising over time, especially with the introduction of new immune therapies, with notable differences among European countries. While these new treatments improve patient outcomes, they also come with a high price tag, which could strain health care budgets. Our results suggest that cost-effectiveness studies will be essential in determining the best and most sustainable treatment strategies in the future.

Surgery with or Without Darolutamide in High-risk and/or Locally Advanced Prostate Cancer: The SUGAR (CCAFU-PR2) Phase 2 Trial Rationale and Protocol.

BACKGROUND: High-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended. OBJECTIVE: The SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT). DESIGN, SETTING, AND PARTICIPANTS: SUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed. RESULTS AND LIMITATIONS: Initial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability. CONCLUSIONS: SUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery. PATIENT SUMMARY: The on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile.

En bloc resection of bladder tumour: the rebirth of past through reminiscence.

PURPOSE: To learn about the history and development of en bloc resection of bladder tumour (ERBT), and to discuss its future directions in managing bladder cancer. METHODS: In this narrative review, we summarised the history and early development of ERBT, previous attempts in overcoming the tumour size limitation, consolidative effort in standardising the ERBT procedure, emerging evidence in ERBT, evolving concepts in treating large bladder tumours, and the future directions of ERBT. RESULTS: Since the first report on ERBT in 1980, there has been tremendous advancement in terms of its technique, energy modalities and tumour retrieval methods. In 2020, the international consensus statement on ERBT has been developed and it serves as a standard reference for urologists to practise ERBT. Recently, high-quality evidence on ERBT has been emerging. Of note, the EB-StaR study showed that ERBT led to a reduction in 1-year recurrence rate from 38.1 to 28.5%. An individual patient data meta-analysis is currently underway, and it will be instrumental in defining the true value of ERBT in treating non-muscle-invasive bladder cancer. For large bladder tumours, modified approaches of ERBT should be accepted, as the quality of resection is more important than a mere removal of tumour in one piece. The global ERBT registry has been launched to study the value of ERBT in a real-world setting. CONCLUSION: ERBT is a promising surgical technique in treating bladder cancer and it has gained increasing interest globally. It is about time for us to embrace this technique in our clinical practice.

Contextualizing Olaparib and Abiraterone in the Current Treatment Landscape for Metastatic Castration-resistant Prostate Cancer.

The PROpel trial assessed the combination of olaparib + abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC. Patient summary: A recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed.

Clinical Trial Protocol for PERFECT: A Randomised Controlled Trial Comparing the Efficiency and Tolerance of Transperineal Fusion Versus Transrectal Imaging-targeted Prostate Biopsies (CCAFU-PR1 Study).

PERFECT is a multicentre randomised controlled clinical trial that evaluates the efficiency of fusion magnetic resonance imaging-targeted biopsies in the transperineal (TP) versus transrectal (TR) approach in terms of the detection of significant cancers. Our study builds on the hypothesis that the TP approach for prostate biopsies has at least the same diagnostic accuracy as the TR approach, with lower morbidity. Here, we describe the clinical protocol, study population, and primary and secondary outcomes.

Immunotherapy in advanced kidney cancer: an alternative meta-analytic method using reconstructed survival data in case of proportional hazard assumption violation.

Background: With the advent of immuno-oncology compounds in randomized trials, we observe more and more survival curves crossing. From a statistical standpoint this corresponds to violation of the proportional hazard assumption. When this occurs, the hazard ratio from the Cox regression is not reliable as an estimate. Herein, we aimed to identify the most appropriate IO-based therapy for metastatic renal cell carcinoma applying an alternative method to overcome the issue of hazard assumption violation for meta-analyses. Methods: Pubmed, EMBASE, Web of Science and Scopus databases were searched. Only phase III randomized clinical trials on IO-IO (nivo-ipi) or IO-TKI combinations were included. An algorithm to obtain survival data from published Kaplan-Meier curves was used to reconstruct data on overall survival (OS), progression-free survival (PFS) and duration of response (DoR). Differences in restricted mean survival time (RMST) were used for comparisons. Results: individual survival data from 4,206 patients from five trials were reconciled. Patients who received nivo-ipi or IO-TKI had better OS, PFS and DoR relative to sunitinib (all p<0.001). Patients who received IO-TKI had similar OS and PFS relative to nivo-ipi, with a 36-month ΔRMST of -0.55 (95% CI: -1.71-0.60; p=0.3) and -1.5 (95% CI: -2.9-0.0; p=0.051) months, respectively. Regarding DoR, patients who received nivo-ipi had longer duration of response relative to IO-TKI, with a 24-month ΔRMST of 1.5 (95% CI: 0.2-2.8; p=0.02) months. Conclusion: Despite overall similar OS and PFS for patients receiving nivo-ipi and IO-TKI combinations, DoR was more favorable in patients who received nivo-ipi compared to IO-TKI. A meta-analysis based on differences in RMST is a useful alternative whenever the proportional hazard assumption is violated. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021241421.

A Plea for Economically Sustainable Evidence-based Guidelines.

The rising costs of cancer care with the introduction of new agents are a challenge. The impact of these costs differs among countries. We compare costs for metastatic prostate cancer, with prices normalized to international dollars, as an example that highlights the need for cost-effectiveness analyses in trials and treatment guidelines.

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis.

The purpose of the review is to summarize the recent data on circulating tumor cells (CTC) use in clinical practice. We performed a systematic literature search using two databases (Medline and Scopus) over the past five years and the following terms: (CTC OR "circulating tumor cells" OR "liquid biopsy") AND prostate. The primary outcome was CTC predictive value for prostate cancer (PC) progression and survival. The secondary outcomes were the CTC predictive value for therapy response and the results of CTC detection depending on the assessment method. In metastatic PC, the CTC count showed itself to be a prognostic marker in terms of clinically important features, namely survival rates and response to treatment. CTC concentration was significantly associated with the overall survival and progression-free survival rates. A strong association between the overall survival or progression-free survival rate and CTC concentration could be observed. Variant-7 androgen receptors-positive (AR-V7-positive) patients showed a poor response to androgen receptor signaling (ARS) inhibitors, but this did not compromise their response to taxanes. In localized PC, only positive Cluster of Differentiantion 82 protein (CD82+) correlated with a higher survival rate. CTC count and AR-V7 expression showed itself to be a valuable biomarker for survival in metastatic PC and response to ARS-inhibitors. CTC diagnostic performance for localized PC or for screening and early detection is not high enough to show additional value over the other biomarkers.

Chemotherapy and advanced androgen blockage, alone or combined, for metastatic hormone-sensitive prostate cancer a systematic review and meta-analysis.

BACKGROUND: The current standard of care for the systemic treatment of metastatic hormone sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT) with either docetaxel or advanced androgen blockage (AAB). Recently, two studies have tested the combination of ADT, docetaxel and AAB (triplet therapy) relative to docetaxel and ADT in this setting. Herein, we aimed to compare the effect on survival outcomes of available systemic treatments for mHSPC. METHODS: A comprehensive search for all published phase III randomized control trials on first line mHSPC that evaluated AAB (TITAN, ARCHES, STAMPEDE, LATITUDE, ENZAMET) or docetaxel (GETUG-AFU15, CHAARTED, STAMPEDE) or their combination (ARASENS, PEACE-1) was conducted PubMed, EMBASE, Web of Science, and Scopus databases up to 15/04/2022. We reconstructed survival data from published Kaplan-Meier curves on overall survival (OS) and progression free survival (PFS) and meta-analyzed docetaxel versus AAB versus triplet therapy (grouping together abiraterone/darolutamide and docetaxel). The outcomes of interest were assessed using differences in restricted mean survival time (ΔRMST) at different time points and Cox regression. RESULTS: Ten trials were included involving 5,544 patients for assessing OS and 5,725 for PFS. Triplet therapy was associated with longer OS when compared to docetaxel (48-month ΔRMST: 2.6; 95 %CI: 1.8,3.4; p < 0.001) but yielded similar OS when compared to AAB (48-month ΔRMST: -0.8; 95 % CI: -1.8, 0.2; p = 0.1). Similarly, triplet therapy was associated with longer PFS when compared to docetaxel (48-month ΔRMST: 10.3; 95 %CI: 9.0,11.6; p < 0.001) but yielded similar PFS when compared to AAB (48-month ΔRMST: 1.1; 95 %CI: -0.2,2.3; p = 0.1). CONCLUSIONS: Overall, we found no OS nor PFS benefit for patients with mHSPC treated with triplet therapy compared to AAB alone, while an advantage emerged for both AAB or triplet therapy relative to docetaxel.

Androgen annihilation versus advanced androgen blockage as first line treatment for metastatic castration resistant prostate cancer: A systematic review and meta-analysis.

BACKGROUND: Despite recent advances in the treatments of metastatic castration resistant prostate cancer (mCRPC), patients' prognosis remains suboptimal and novel treatment combinations are under scrutiny. On this matter, the recent ACIS trial tested the role of abiraterone plus apalutamide (androgen annihilation) in addition to androgen deprivation therapy, versus abiraterone plus androgen deprivation therapy. Herein, we performed a meta-analysis to compare overall survival (OS) and progression free survival (PFS) among patients who received androgen annihilation versus advanced androgen blockage (abiraterone or enzalutamide), in addition to conventional androgen deprivation therapy. METHODS: A comprehensive search for all published phase III randomized control trials on first line mCRPC that evaluated advanced androgen blockage (COU-AA-302, PREVAIL) or androgen annihilation (ACIS) was conducted PubMed, EMBASE, Web of Science, and Scopus databases up to 31/12/2021. We reconstructed survival data from published Kaplan-Meier curves on overall survival (OS) and progression free survival (PFS) and meta-analyzed androgen annihilation versus advanced androgen blockage (grouping together abiraterone and enzalutamide) versus androgen deprivation therapy. The outcomes of interest were assessed using difference in restricted mean survival time (ΔRMST) at different time points. RESULTS: Three trials were included involving 3787 patients. Overall, patients receiving androgen annihilation exhibited similar OS compared to advanced androgen blockage: ΔRMST at 36 months of - 0.2 (95%CI: -1.1, 0.8, p = 0.8). At 36 months, relatively to ADT alone, patients receiving androgen annihilation or advanced androgen blockage exhibited longer OS: ΔRMST of 1.6 (95%CI: 0.6, 2.7, p = 0.002) and 1.8 months (95%CI: 1.1, 2.5, p < 0.001), respectively. Patients receiving androgen annihilation exhibited better PFS compared to advanced androgen blockage: ΔRMST at 36 months of 2.4 months (95%CI: 1.0, 3.8, p = 0.001). CONCLUSION: We found no OS benefit for patients with mCRPC treated with androgen annihilation compared to advanced androgen blockage. This might be ascribed to an increased rate of other cause mortality that might determine the absence of an OS benefit or to the efficacy of second line therapies. Optimal treatment sequence and patient selection for androgen annihilation remain open points. However, a PFS benefit was found in case of combination therapy, whose clinical meaning is not yet clear.

Multidisciplinary team referral at diagnosis for patients with non-metastatic renal cell carcinoma.

BACKGROUND: To date, multidisciplinary team (MDT) evaluation, enrollment in trials evaluating the role of perioperative therapies and deferred active treatments represent accepted strategies for patients with Renal Cell Carcinoma (RCC), which are under investigation to maximize cancer control and implement health care policies and value-based care. Here, we aimed to identify subgroups of patients with RCC who may benefit from early referral for MDT evaluation at diagnosis in light of an increased risk of recurrence relative to the risk of dying of other causes. METHODS: We relied on a prospective dataset including patients diagnosed with RCC from 1998 to 2019 and treated by means of surgery alone at a tertiary referral center. The risk of other cause mortality (OCM) was evaluated against the risk of distant metastasis over time by means of the Weibull regression. Patients were stratified based on clinical stage (cT1a; cT1b; cT2; cT3-4), age (<60; 60-70; >70) and comorbidities [Charlson comorbidity index (CCI) 0 vs. ≥1]. For each combination of cT stage, age, and CCI, the potential need for an MDT referral was defined when the risk of recurrence exceeded the risk of OCM within the lower limit of the 95% CI of the meantime to recurrence. MAIN FINDINGS: Overall, 1,162 (51%) patients had no comorbidities. Median follow-up was 7 years. Patients who would benefit most from an MDT evaluation are those diagnosed with A) cT3-4 disease (any age or comorbidity) or B) cT2 cancers if healthy and younger than 70 years or younger than 60 years with at least 1 comorbidity or C) cT1b if younger than 60 years and without comorbidities. CONCLUSIONS: Our findings can help selecting the optimal candidates for multidisciplinary evaluations and to consider RCC patients for clinical trials, deferred treatment, and treatment policy improvement. Also, our findings can be useful in the case of major healthcare disruptions, such as pandemics.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Periprostatic Adipose Tissue Displays a Chronic Hypoxic State that Limits Its Expandability.

White adipose tissue accumulates at various sites throughout the body, some adipose tissue depots exist near organs whose function they influence in a paracrine manner. Prostate gland is surrounded by a poorly characterized adipose depot called periprostatic adipose tissue (PPAT), which plays emerging roles in prostate-related disorders. Unlike all other adipose depots, PPAT secretes proinflammatory cytokines even in lean individuals and does not increase in volume during obesity. These unique features remain unexplained because of the poor structural and functional characterization of this tissue. This study characterized the structural organization of PPAT in patients compared with abdominopelvic adipose tissue (APAT), an extraperitoneal adipose depot, the accumulation of which is correlated to body mass index. Confocal microscopy followed by three-dimensional reconstructions showed a sparse vascular network in PPAT when compared with that in APAT, suggesting that this tissue is hypoxic. Unbiased comparisons of PPAT and APAT transcriptomes found that most differentially expressed genes were related to the hypoxia response. High levels of the hypoxia-inducible factor 2α confirmed the presence of an adaptive response to hypoxia in PPAT. This chronic hypoxic state was associated with inflammation and fibrosis, which were not further up-regulated by obesity. This fibrosis and inflammation explain the failure of PPAT to expand in obesity and open new mechanistic avenues to explain its role in prostate-related disorders, including cancer.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Managing Discordant Findings Between Multiparametric Magnetic Resonance Imaging and Transrectal Magnetic Resonance Imaging-directed Prostate Biopsy-The Key Role of Magnetic Resonance Imaging-directed Transperineal Biopsy.

BACKGROUND: Discordant findings between multiparametric magnetic resonance imaging (mpMRI) and transrectal image-guided biopsies of the prostate (TRUS-P) may result in inadequate risk stratification of localized prostate cancer. OBJECTIVE: To assess transperineal image-guided biopsies of the index target (TPER-IT) in terms of disease reclassification and treatment recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cases referred for suspicion or treatment of localized prostate cancer were reviewed in a multidisciplinary setting, and discordance was characterized into three scenarios: type I-negative biopsies or International Society of Urological Pathology (ISUP) grade 1 cancer in Prostate Imaging Reporting and Data System (PI-RADS) ≥4 index target (IT); type II-negative biopsies or ISUP grade 1 cancer in anterior IT; and type III-<3 mm stretch of cancer in PI-RADS ≥3 IT. Discordant findings were characterized in 132/558 (23.7%) patients after TRUS-P. Of these patients, 102 received reassessment TPER-IT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objective was to report changes in treatment recommendations after TPER-IT. Therefore, cores obtained by primary TRUS-P and TPER-IT were analyzed in terms of cancer detection, ISUP grade, and Cambridge Prognostic Group classification using descriptive statistics. RESULTS AND LIMITATIONS: TPER-IT biopsies that consisted of fewer cores than the initial TRUS-P (seven vs 14, p < 0.0001) resulted in more cancer tissue materials for analysis (56 vs 42.5 mm, p = 0.0003). As a result, 40% of patients initially considered for follow-up (12/30) and 49% for active surveillance (30/61) were reassigned after TPER-IT to surgery or intensity-modulated radiotherapy. CONCLUSIONS: Nonconcordance between pathology and imaging was observed in a significant proportion of patients receiving TRUS-P. TPER-IT better informed the presence and grade of cancer, resulting in a significant impact on treatment recommendations. A multidisciplinary review of mpMRI and TRUS-P findings and reassessment TPER-IT in type I-II discordances is recommended. PATIENT SUMMARY: In this report, patients with suspicious imaging of the prostate, but no or well-differentiated cancer on transrectal image-guided -biopsies, were offered transperineal image-guided biopsies for reassessment. We found that a large share of these had a more aggressive cancer than initially suspected. We conclude that discordant results warrant reassessment transperineal image-guided biopsies as these may impact disease risk classification and treatment recommendations.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

OBJECTIVE: To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. METHODS: From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. RESULTS: Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. CONCLUSIONS: PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.