Magnetic resonance imaging-ultrasound fusion guided focal cryoablation for men with intermediate-risk prostate cancer.

INTRODUCTION: Focal therapy (FT) is a form of ablative treatment offered to men with localized, organ-confined prostate cancer (CaP). Pelvic multiparametric magnetic resonance imaging (mpMRI) and mpMRI/transrectal ultrasound fusion (MRI-US) guidance enable the precise delivery of FT with limited ablation of adjacent benign tissue or vital genitourinary structures. This article presents our findings on using MRI-US to perform FT as a primary treatment for men with intermediate-risk CaP. METHODS: Thirty-six men underwent MRI-US fusion-guided FT cryoablation at a single center from 2018 to 2023 as a primary treatment for intermediate-risk CaP. Following FT, quarterly prostate-specific antigen (PSA) testing and a 6 to 9 month mpMRI and combined MRI-US targeted and systematic biopsy were performed. Oncological outcomes were determined using several endpoints containing biochemical recurrence, imaging failure, and pathological failure. Functional outcomes were measured using reported erectile dysfunction/potency rates, urinary incontinence rates, and the American Urologic Association Symptom Score (AUA-SS) and Sexual Health Inventory for Men (SHIM) indices. RESULTS: Median follow-up was 29.1 months, most (75%) of whom had grade group 2 CaP. Out of the 36 men, 32 (88.9%) completed the combined MRI-targeted and systematic biopsy follow-up after treatment. The study had no major complications, but 12 (33.3%) patients experienced Clavien-Dindo grade II or lower complications. For oncological outcomes, 6 (16.7%) men had biochemical recurrence, 9 (25%) showed imaging failure, and 8 (22.2%) met the criteria for positive biopsy- out-of-field vs. in-field. 88.2% of previously potent patients remained potent postoperatively at 12 months. All patients were continent at 12 months. There were no statistically significant changes in the AUA-SS and SHIM scores postoperatively. CONCLUSION: MRI-US-guided cryoablation to target lesions in intermediate-risk CaP appears to be a safe treatment option, with functional outcomes indicating minimal short and intermediate-term morbidity and acceptable oncological outcomes. However, despite close monitoring and follow-up, there is still a limitation in accurately predicting/detecting pathological failure after FT. The long-term durability of FT for intermediate-risk, organ-confined CaP remains uncertain.

Reliability of Systematic and Targeted Biopsies versus Prostatectomy.

Systematic Biopsy (SBx) has been and continues to be the standard staple for detecting prostate cancer. The more expensive MRI guided biopsy (MRITBx) is a better way of detecting cancer. The prostatectomy can provide an accurate condition of the prostate. The goal is to assess how reliable SBx and MRITBx are vis à vis prostatectomy. Graded Gleason scores are used for comparison. Cohen's Kappa index and logistic regression after binarization of the graded Gleason scores are some of the methods used to achieve our goals. Machine learning methods, such as classification trees, are employed to improve predictability clinically. The Cohen's Kappa index is 0.31 for SBx versus prostatectomy, which means a fair agreement. The index is 0.34 for MRITBx versus prostatectomy, which again means a fair agreement. A direct comparison of SBx versus prostatectomy via binarized graded scores gives sensitivity 0.83 and specificity 0.50. On the other hand, a direct comparison of MRITBx versus prostatectomy gives sensitivity 0.78 and specificity 0.67, putting MRITBx on a higher level of accuracy. The SBx and MRITBx do not yet match the findings of prostatectomy completely, but they are useful. We have developed new biomarkers, considering other pieces of information from the patients, to improve the accuracy of SBx and MRITBx. From a clinical point of view, we provide a prediction model for prostatectomy Gleason grades using classification tree methodology.

Traditional and novel imaging modalities for advanced prostate cancer: A critical review.

Accurate detection of metastatic prostate cancer in the setting of preoperative staging as well as posttreatment recurrence is crucial to provide patients with appropriate and timely treatment of their disease. This has traditionally been accomplished with a combination of computed tomography, magnetic resonance imaging, and bone scan. Recently, more novel imaging techniques have been developed to help improve the detection of advanced and metastatic prostate cancer. This review discusses the efficacy of the traditional imaging modalities as well as the novel imaging techniques in detecting metastatic prostate cancer. Articles discussed were gathered through a formal PubMed search.

Real-Time and Delayed Imaging of Tissue and Effects of Prostate Tissue Ablation.

PURPOSE OF REVIEW: Prostate ablation is increasingly being utilized for the management of localized prostate cancer. There are several energy modalities with varying mechanism of actions which are currently used for prostate ablation. Prostate ablations, whether focal or whole gland, are performed under ultrasound and/or MRI guidance for appropriate treatment plan execution and monitoring. A familiarity with different intraoperative imaging findings and expected tissue response to these ablative modalities is paramount. In this review, we discuss the intraoperative, early, and delayed imaging findings in prostate from the effects of prostate ablation. RECENT FINDINGS: The monitoring of ablation both during and after the therapy became increasingly important due to the precise targeting of the target tissue. Recent findings suggest that real-time imaging techniques such as MRI or ultrasound can provide anatomical and functional information, allowing for precise ablation of the targeted tissue and increasing the effectiveness and precision of prostate cancer treatment. While intraprocedural imaging findings are variable, the follow-up imaging demonstrates similar findings across various energy modalities. MRI and ultrasound are two of the frequently used imaging techniques for intraoperative monitoring and temperature mapping of important surrounding structures. Follow-up imaging can provide valuable information about ablated tissue, including the success of the ablation, presence of residual cancer or recurrence after the ablation. It is critical and helpful to understand the imaging findings during the procedure and at different follow-up time periods to evaluate the procedure and its outcome.

Salvage Radical Prostatectomy after Primary Focal Ablative Therapy: A Systematic Review and Meta-Analysis.

CONTEXT: Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients. OBJECTIVE: To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure. EVIDENCE ACQUISITION: A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment. EVIDENCE SYNTHESIS: 12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively. CONCLUSION: Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments. PATIENT SUMMARY: We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.

App-Based Yoga of Immortals: A Novel, Easy-to-use Intervention in the Management of Urinary Incontinence.

OBJECTIVE: To study the effectiveness Yoga of Immortals (YOI) intervention in participants with urinary incontinence (UI) of all types. YOI uniquely combines specific yogic postures, breathing exercises, sound therapy & meditation and is practiced by many for general well-being. MATERIALS AND METHODS: In this App-based cohort study, a survey was sent to the YOI app subscribers. Those who identified with UI and consented were sent the ICIQ-UI- SF (for mean symptom score & severity of UI), and the ICIQ-LUTS-QOL (for impact of UI on QOL) Questionnaires at baseline, 4, and 8 weeks. Global impression of improvement was assessed by PGI-I scale. RESULTS: 258/422 participants (18-74 years) were included and showed significant decrease in mean scores on the ICIQ-UI-SF (4.06 ± 0.24 at baseline; 2.90 ± 0.22 at 4-weeks [p ≤ 0.001] and 3.44 ± 0.23 at 8 weeks [p ≤ 0.001]) and ICIQ-LUTS-QOL (28.36± 0.74 at baseline; 24.46± 0.70 at 4-weeks [p ≤ 0.001] and 25.78± 0.70 at 8 weeks [p≤ 0.001]). Additionally, the 55-60 year subgroup also had significant decrease in mean scores on ICIQ-LUTS-QOL (25.06 ±1.20 at base line; 21.69 ± 1.07 at 4 weeks [p ≤ 0.01] and 22.28 ± 0.96 at 8 weeks [p ≤ 0.01]). CONCLUSION: YOI intervention resulted in significant improvement in mean scores on ICIQ-LUTS-QOL; ICIQ-UI-SF; frequency and severity of urinary leak; and daily life activity. Majority of the participants felt 'very much better' on PGI-scale. Being app- based, it has the added advantage of the ability to be used anytime and anywhere.

Schema and cancer detection rates for transperineal prostate biopsy templates: a review.

Prostate cancer (PCa) is the most common noncutaneous malignancy in men and is the second leading cause of cancer mortality in men in the United States. Current practice requires histopathological confirmation of cancer achieved through biopsy for diagnosis. The transrectal approach for prostate biopsy has been the standard for several decades. However, the risks and limitations of transrectal biopsies have led to a recent resurgence of transperineal prostatic biopsies. Recent studies have demonstrated the transperineal approach for prostate biopsies to be effective, associated with minimal complications and superior in several aspects to traditional transrectal biopsies. While sextant and extended sextant templates are widely accepted templates for transrectal biopsy, there are a diverse set of transperineal biopsy templates available for use, without consensus on the optimal sampling strategy. We aim to critically appraise the salient features of established transperineal biopsy templates.

Hundred years of transperineal prostate biopsy.

The earliest recorded efforts to biopsy prostate, in the early 20th century, were made through transperineal (TP) approach, with open perineal prostate biopsy (PBx) being considered the gold standard for prostate cancer (PCa) diagnosis in that era. Later, to minimize morbidity and increase diagnostic accuracy, several technical modifications and transrectal ultrasound (TRUS) assistance were incorporated. However, in the 1980s, the transrectal (TR) approach became the predominant PBx method following the introduction of TRUS-TR PBx with sextant sampling, providing a convenient and efficacious method for prostate sampling. With modernization of PCa diagnosis, a recent resurgence of the TP PBx has been observed, driven primarily by TR drawbacks of infectious complications and sampling limitations. TP PBx is rapidly emerging as the new PBx standard, being officially recommended as the initial approach for biopsy in Europe and is increasingly being conducted and studied in the United States. The modern era of TP PBx is based on the improvements in local anesthesia techniques, TP access systems, and robotic assistance. These modifications and advancements have improved the ease of use, patient comfort, and diagnostic outcomes with TP PBx. Herein, we present a history of the evolution of TP PBx spanning over 100 years and explore the basis of the technique that merits future utilization.

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.

Does the type of biopsy used for diagnosis impact subsequent treatment selection in prostate cancer patients?

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) targeted biopsy has emerged as an augmentation to systematic prostate biopsy (SBx) with improved diagnostic accuracy. The purpose of this study was to determine whether biopsy modality impacted management of prostate cancer (PCa). METHODS: We performed a retrospective review of patients with newly diagnosed non-metastatic PCa at our institution (2014-2020). Either ultrasound-guided 12-core SBx or SBx plus ≥1targeted biopsy cores from identifiable lesions on mpMRI were performed. Patients were managed with active surveillance (AS), radiation therapy (RT), or radical prostatectomy (RP). Multivariate logistic and multinomial regression analyses were performed. RESULTS: Of 578 patients, 221(38%) proceeded with AS, 121(21%) received RT, and 236(41%) underwent RP. Median age and prostate-specific antigen (PSA) were 65.4 years and 7.2 ng/mL, respectively. On multivariate analysis, biopsy type did not predict decision to pursue treatment (p=.951). On multinomial regression analysis, biopsy type did not predict selection of AS over RP (p=.973) or RT over RP (p=.813). Alternatively, age, grade group, and PSA were significant predictors of management selection. CONCLUSIONS: Biopsy technique did not impact management for patients with new PCa diagnosis. Despite paradigm shifts in obtaining tissue diagnosis, age, PSA, and grade group remain valuable indices for shared decision-making and counseling patients with PCa.

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.

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.

Current Opinion Regarding Multidisciplinary Cancer Clinic Utilization for the Management of Prostate Cancer.

OBJECTIVES: Multidisciplinary cancer clinic (MDC) is an evaluation option for the management of prostate cancer (PCa). The purpose of MDC is to provide the patient with a comprehensive assessment and risk/benefit discussion of all pertinent treatment options. Our objective was to obtain a contemporary measure and analysis of urologists' opinion regarding PCa MDC. MATERIAL AND METHODS: We created a 14-item questionnaire for respondent baseline characteristics, subjective and objective inquiries regarding MDC for PCa management. The survey was distributed through email to members of the Society of Urologic Oncology and the Endourological Society. Data were analyzed using R (R Core team, 2017). RESULTS: One hundred and seven (51%) respondents reported participation in MDC; the majority of which were male (97.6%), academic (61.4%) urologists with urologic oncology fellowship training (50%), and >20 years in practice (40.3%). MDC patients were most commonly referrals (78.5%) and with high-risk disease (Gleason sum 8-10) (83.2%). A majority of the respondents felt that MDC was very or extremely beneficial for PCa research (45% and 19%, respectively) and treatment (35% and 20%, respectively). Responses dissuading the use of MDC included lack of infrastructure (41%) and time commitment (21%). On multivariate analysis, urologists with >10 years in practice were less likely to find MDC beneficial in the management of PCa (11-20 years, P = 0.028 and >20 years P = 0.009). CONCLUSION: A contemporary sampling of urologists' opinion and practice patterns alludes to the benefits that advocate for and the resource demand that hinders routine use of MDC for PCa evaluation. Urologist training and practice environment can affect participation in PCa MDC.

MRI-guided focal laser ablation of prostate cancer: a prospective single-arm, single-center trial with 3 years of follow-up.

PURPOSE: We aimed to assess post-interventional and 36-month follow-up results of a single-center, single-arm, in-bore phase I trial of focal laser ablation (FLA) guided by multiparametric magnetic resonance imaging (mpMRI). METHODS: FLA procedures were done in-bore MRI using a transperineal approach. Primary endpoints were feasibility and safety expressed as lack of grade 3 complications. Secondary endpoints were changes in international prostate symptom score (IPSS), sexual health inventory for men (SHIM), quality of life (QoL) scores, and serum prostate specific antigen (PSA) levels. Treatment outcomes were assessed by combined mpMRI-ultrasound fusion-guided and extended sextant systematic biopsy after 12, 24, and optionally after 36 months. RESULTS: Fifteen participants were included. Seven patients (46.67%) had Gleason 3+3 and 8 patients (53.33%) had Gleason 3+4 cancer. All patients tolerated the procedure well, and no grade 3/4 complications occurred. All grade 1 and 2 complications were transient and resolved completely. There was no significant change in mean IPSS from baseline (-1, p = 0.460) and QoL (0, p = 0.441) scores following FLA but there was a significant drop in mean SHIM scores (-2, p = 0.010) compared to pretreatment baselines. Mean PSA significantly decreased after FLA (-2.5, p < 0.001). Seven out of 15 patients (46.67%) had residual cancer in, adjacent, or in close proximity to the treatment area (1 × 4+3=7, 1 × 3+4=7, and 5 × 3+3=6). Four out of 15 patients (26.67%) underwent salvage therapy (2 repeat FLA, 2 radical prostatectomy). CONCLUSION: After 3 years of follow-up we conclude focal laser ablation is safe and feasible without significant complications.

How does a prebiopsy mri approach for prostate cancer diagnosis affect prostatectomy upgrade rates?

BACKGROUND: To compare the pathologic upgrade and downgrade rates after radical prostatectomy (RP) between patients diagnosed by prebiopsy prostate MRI followed by a combination of systematic and fusion biopsy (ComBx) versus patients undergoing systematic biopsy only (SBx). METHODS: A retrospective review of men undergoing RP at our institution between Jan 2014 and Mar 2020 was performed. These patients were separated into two independent cohorts based on two approaches: Patients receiving prebiopsy prostate MRI during initial evaluation and those who did not receive MRI. Patients with positive MRI findings underwent subsequent ComBx to confirm diagnosis while those without MRI underwent standard trans-rectal ultrasound (TRUS) guided systematic 12-core biopsy (SBx). Primary outcomes were rates of pathological upgrade (prostatectomy grade higher than grade determined at time of biopsy) and downgrade (prostatectomy grade lower than biopsy grade). RESULTS: A total of 213 patients undergoing radical prostatectomy, 91 diagnosed via a prebiopsy MRI and ComBx approach and 122 diagnosed by a traditional SBx approach, were included in the study. There was no significant difference between age, PSA, or positive family history between the two cohorts. Of the 91 patients who received prebiopsy MRI, 88 patients were determined to have a PIRADS 4 or 5 lesion. Patients who received MRI and subsequent ComBx had a lower rate of any pathological upgrade after RP (9.89% vs. 22.13%, P = 0.018) without a significant difference in pathologic downgrade rate (28.57% vs. 18.85%, P = 0.095). On multivariable logistic regression, receiving prebiopsy MRI during initial evaluation was the single negative independent predictor of pathologic upgrade (OR = 0.23, P = 0.017). A prebiopsy MRI approach was also the single predictor of pathologic downgrade (OR = 3.13, P = 0.041). CONCLUSIONS: Patients receiving prebiopsy MRI during prostate cancer evaluation were less likely to have their PCa upgraded. Furthermore, although diagnosis via MRI and subsequent ComBx was associated with an increased rate of downgrades after RP, relatively few resulted in a downgrade from clinically significant to clinically insignificant cancer.

Prostate cancer biomarkers and multiparametric MRI: is there a role for both in prostate cancer management?

Several advancements have been made in recent years with regards to the detection and evaluation of prostate cancer (PCa). The low specificity of prostate specific antigen (PSA) has left much to be desired in a test, but a boom in novel biomarkers has made screening and surveillance more complicated. Several attempts at identifying a niche for these tests has helped somewhat, but much is still undetermined about the benefit that each test provides. In addition to laboratory tests, advancements in multiparametric magnetic resonance imaging (mpMRI) and PIRADSv.2 scoring have provided significant benefit to the evaluation of PCa. With the widespread use of prostate imaging, it is important to re-evaluate the impact of novel biomarkers in the context of furthering PCa screening and management. In this review, we aim to assess the influence mpMRI has on the role of nine different novel biomarkers in the detection and evaluation of PCa. We performed a review of current peer-reviewed literature to assess this question. Much data has been published on the role of these tests, allowing for their placement into one of three best-fit categories: tests for biopsy-naïve men (Prostate Health Index, Mi Prostate Score, 4K Score); tests for men with prior negative biopsies (ConfirmMDx, Progensa PCA3); and men on active surveillance (OncotypeDx, Prolaris, Decipher). Data on the role of these tests with the use of mpMRI have not been comprehensive and excludes several of the markers. More research is needed to determine the combined impact mpMRI and the novel biomarkers on the evaluation and management of PCa.

Utilization of focal therapy for patients discontinuing active surveillance of prostate cancer: Recommendations of an international Delphi consensus.

BACKGROUND: With the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS). METHODS: A 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement. RESULTS: Fifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community. CONCLUSIONS: FT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS.

Tobacco smoking induces metabolic reprogramming of renal cell carcinoma.

BACKGROUNDClear cell renal cell carcinoma (ccRCC) is the most common histologically defined renal cancer. However, it is not a uniform disease and includes several genetic subtypes with different prognoses. ccRCC is also characterized by distinctive metabolic reprogramming. Tobacco smoking (TS) is an established risk factor for ccRCC, with unknown effects on tumor pathobiology.METHODSWe investigated the landscape of ccRCCs and paired normal kidney tissues using integrated transcriptomic, metabolomic, and metallomic approaches in a cohort of white males who were long-term current smokers (LTS) or were never smokers (NS).RESULTSAll 3 Omics domains consistently identified a distinct metabolic subtype of ccRCCs in LTS, characterized by activation of oxidative phosphorylation (OXPHOS) coupled with reprogramming of the malate-aspartate shuttle and metabolism of aspartate, glutamate, glutamine, and histidine. Cadmium, copper, and inorganic arsenic accumulated in LTS tumors, showing redistribution among intracellular pools, including relocation of copper into the cytochrome c oxidase complex. A gene expression signature based on the LTS metabolic subtype provided prognostic stratification of The Cancer Genome Atlas ccRCC tumors that was independent of genomic alterations.CONCLUSIONThe work identified the TS-related metabolic subtype of ccRCC with vulnerabilities that can be exploited for precision medicine approaches targeting metabolic pathways. The results provided rationale for the development of metabolic biomarkers with diagnostic and prognostic applications using evaluation of OXPHOS status. The metallomic analysis revealed the role of disrupted metal homeostasis in ccRCC, highlighting the importance of studying effects of metals from e-cigarettes and environmental exposures.FUNDINGDepartment of Defense, Veteran Administration, NIH, ACS, and University of Cincinnati Cancer Institute.