Role of multiparametric MRI in long-term surveillance following focal laser ablation of prostate cancer.

OBJECTIVE: Determine the multiparametric magnetic resonance imaging (mpMRI) appearance of the prostate following focal laser ablation (FLA) for PCa and to identify imaging characteristics associated with recurrent disease. METHODS: Retrospective analysis of patients who underwent FLA for low-intermediate risk PCa between 2010 and 2014 was performed. Early (median 4 months) and late mpMRI (median 49 months) follow-up were qualitatively assessed for T2-weighted, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) appearances and also compared to corresponding PSA values and biopsy results. RESULTS: 55 cancers were treated in 54 men (mean age 61.0 years). Early mpMRI was performed in 30 (54.5%) patients while late follow-up mpMRI in 42 (84%). Ill-defined scarring with and without atrophy at the treatment site were the most common appearances. In patients with paired MRI and biopsy, one of four patients with clinically significant PCa on biopsy (≥GG2 or≥6 mm GG1) showed hyperenhancement or restricted diffusion at early follow-up. At late follow-up, positive biopsies were seen in 5/8 (63%) cases with hyperenhancement and 5/6 (83%) cases with restricted diffusion at the treatment site. PSA change was not associated with biopsy results at either time point. CONCLUSION: mpMRI is able to document the morphological and temporal changes following focal therapy. It has limited ability to detect recurrent disease in early months following treatment. Late-term mpMRI is sensitive at identifying patients with recurrent disease. Small sample size is, however, a limitation of the study. ADVANCES IN KNOWLEDGE: Implementing MRI in follow-up after FT may be useful in predicting residual or recurrent PCa and therefore provide reliable outcome data.

Associations between self-reported physical activity, quality of life, and emotional well-being in men with prostate cancer on active surveillance.

OBJECTIVE: The relationship between physical activity (PA) and quality of life (QOL) relative to active treatment for prostate cancer (PCa) has been well-studied; however, little is known about this relationship during active surveillance (AS). Moreover, whether PA is associated with better emotional well-being (EWB) in men with low-risk PCa requires further investigation. Accordingly, we examined the association between self-reported PA and the average change in QOL and EWB over time during AS. METHODS: A total of 630 men on AS were included in this retrospective, longitudinal study from AS initiation until AS discontinuation. Generalized estimated equations were used to determine the association between self-reported PA (independent variable) and QOL and EWB (dependent variables) over time, adjusting for participants' age. RESULTS: QOL was higher over time in active ( ß^ (95%CI) = 1.14 (0.11, 2.16), P = .029) and highly active participants ( ß^ (95%CI) = 1.62 (0.58, 2.67), P = .002) compared to their inactive counterparts. Highly active participants had 55% greater odds of experiencing high EWB relative to inactive participants (OR (95%CI) = 1.55 (1.11, 2.16), P = .010). In men with low EWB at baseline (median = 3 months after diagnosis), the highest levels of PA (>1000 metabolic equivalent-minutes per week) were associated with high EWB over time (OR (95%CI) = 2.17 (1.06, 4.46), P = .034). CONCLUSIONS: These data further support the importance of PA as a supportive care strategy for men on AS. Our findings suggest that engaging in higher volumes of PA post-diagnosis may be beneficial particularly for men exhibiting low emotional well-being early on during AS.

Pfilates and Hypopressives for the Treatment of Urinary Incontinence After Radical Prostatectomy: Results of a Feasibility Randomized Controlled Trial.

BACKGROUND: Urinary incontinence (UI) is an important side effect of radical prostatectomy (RP). Coactivation of surrounding muscles via novel techniques for pelvic floor rehabilitation known as Pfilates and Hypopressives has not been compared to pelvic floor muscle exercises (PFMXs) for UI. OBJECTIVE: To assess the feasibility and efficacy of isolated PFMXs with and without the addition of Pfilates and Hypopressives on UI recovery following RP. DESIGN: Randomized controlled trial. SETTING: Participants were recruited from a community and tertiary cancer center in Toronto, Canada. PARTICIPANTS: A total of 226 patients undergoing RP were assessed for eligibility. One hundred twenty-two patients were eligible and 50 consented to participate; 37 participants completed the trial. METHODS: Participants were randomized to either isolated PFMX (control) or PFMX plus Pfilates and Hypopressives (advanced pelvic floor exercises; APFX) groups. PFMX participants (n = 25) received instructions for isolated pelvic floor contractions starting with 30 contractions per day during weeks 1 to 2 up to 180 per day for weeks 7 to 26. The APFX group (n = 25) received a comparable volume of exercises. MAIN OUTCOME MEASUREMENTS: Feasibility was assessed by rates of recruitment, adverse events, and study-arm compliance. Information about UI and quality of life was collected 1 week before surgery and at 2, 6, 12, and 26 weeks after surgery. RESULTS: The recruitment rate was 41%, adherence to the PFMXs and APFXs was >70%, and there were no reported adverse events. Between-group differences were observed in the frequency of self-reported 24-hour urinary leakage (rate ratio 0.45, 95% confidence interval [CI] 0.2-0.98) and during waking hours (rate ratio 0.43, 95% CI 0.20-0.91) at 26 weeks after surgery favoring APFX. CONCLUSIONS: Pfilates and Hypopressives are feasible in men undergoing RP, and preliminary data suggest a potential benefit in aiding recovery of urinary control. Larger studies with longer follow-up are warranted. LEVEL OF EVIDENCE: II.

Influence of physical activity on active surveillance discontinuation in men with low-risk prostate cancer.

PURPOSE: Epidemiologic data suggest that high levels of physical activity (PA) may reduce the risk of disease progression in men with prostate cancer (PCa), but it is unknown whether PA can delay the requirement for definitive treatment for those on active surveillance (AS). We investigated the influence of PA post-diagnosis on AS discontinuation in men with low-risk disease. METHODS: The effect of PA on the time to AS discontinuation was assessed in 421 patients, of whom 107 underwent additional PCa treatment over a median of 2.5 years. RESULTS: Using Cox regression models, we found that PA was not significantly associated with time to curative treatment initiation. Prostate-specific antigen (PSA) most proximal to AS initiation (HR, 1.11; 95% CI 1.03 to 1.21) and the number of positive cores (HR, 1.34; 95% CI 1.12 to 1.61) at diagnosis were associated with a significantly increased risk of discontinuing AS. CONCLUSION: Our findings suggest that PA during AS for PCa does not significantly influence time to curative treatment.

Magnetic resonance guided focused high frequency ultrasound ablation for focal therapy in prostate cancer - phase 1 trial.

OBJECTIVES: To evaluate the feasibility and safety of focal therapy for low-intermediate risk prostate cancer (PCa) with magnetic resonance-guided high frequency focused ultrasound (MRgFUS) METHODS: This IRB-approved phase 1 prospective study enrolled eight patients with prostate specific antigen (PSA) ≤ 10 ng/ml, ≤ cT2a and Gleason score ≤ 7 (4 + 3) disease following informed consent. Under MRI guidance, focused high frequency ultrasound energy was delivered to ablate the target tissue. Treatment-related adverse events were recorded. Oncologic outcomes were evaluated with multiparametric MRI, PSA and TRUS biopsy at 6 months following treatment. RESULTS: Ten target lesions [six Gleason 6 lesions, two Gleason 7 (3 + 4) and two Gleason 7 (4 + 3)] were treated in eight men (prostate volume range, 25-50 cc; mean MRI time, 248 min per patient; mean sonication duration, 65 min). Mean target volume was 2.7 cc and mean post-treatment non-perfused volume was 4.3 cc. Quality of life parameters were similar between baseline and 6 months in 6/8 patients. All treated regions were negative on MRI; 4/8 patients and 6/10 target lesions (60%) were clear of disease on biopsy. One patient with 2-mm Gleason 8 disease in one of five cores from treatment site (4 + 3 disease at baseline) subsequently underwent prostatectomy with negative surgical margins. Three patients with low volume (5-15%) Gleason 6 residual disease were offered active surveillance. Mean PSA decreased from 5.06 at baseline to 3.4 ng/ml at 6 months. CONCLUSION: MRgFUS is a feasible and safe method of noninvasively ablating low-intermediate risk PCa with acceptable short-term oncologic outcomes. KEY POINTS: • Focal therapy selectively ablates locally confined, clinically significant index lesion with a margin while sparing rest of gland and adjacent vital structures. • Magnetic resonance-guided focused high frequency ultrasound surgery (MRgFUS) combines MRI with HIFU. • MRgFUS provides ability to monitor treatments in real time and allows a targeted approach for focal ablation. • MRgFUS is a feasible, safe method of noninvasively ablating low-intermediate risk PCa. • MRgFUS provides acceptable oncologic outcomes at 6 months.

Next-generation prostate cancer risk calculator for primary care physicians.

INTRODUCTION: Current prostate cancer risk calculators are limited in impact because only a probability of having prostate cancer is provided. We developed the next generation of prostate cancer risk calculator that incorporates life expectancy in order to better evaluate prostate cancer risk in context to a patient's age and comorbidity. METHODS: We combined two cohorts to develop the new risk calculator. The first was 5638 subjects who all underwent a prostate biopsy for prostate cancer detection. The second was 979 men diagnosed with prostate cancer with long-term survival data. Two regression models were used to create multivariable nomograms and an online prostate cancer risk calculator was developed. RESULTS: Of the 5638 patients who underwent a prostate biopsy, 629 (11%) were diagnosed with aggressive prostate cancer (Gleason Score 7[4+3] or more). Of the 979 patients who underwent treatment for prostate cancer, the 10-year overall survival (OS) was 49.6% (95% confidence interval [CI] 46.6-52.9). The first multivariable nomogram for cancer risk had a concordance index of 0.74 (95% CI 0.72, 0.76), and the second nomogram to predict survival had a concordance index of 0.71 (95% CI 0.69-0.72). The next-generation prostate cancer risk calculator was developed online and is available at: http://riskcalc.org/ProstateCA_Screen_Tool. CONCLUSIONS: We have developed the next-generation prostate cancer risk calculator that incorporates a patient's life expectancy based on age and comorbidity. This approach will better evaluate prostate cancer risk. Future studies examining other populations will be needed for validation.

Psychological distress and lifestyle disruption in low-risk prostate cancer patients: Comparison between active surveillance and radical prostatectomy.

OBJECTIVE: To quantify distress in men treated with radical prostatectomy (RP) or active surveillance (AS). METHODS: In a retrospective cross-sectional design, we assessed men through questionnaire and investigator-designed questions. RESULTS: RP patients worried more about cancer spread than AS patients. RP patients were influenced by friends for treatment decision, whereas AS patients were influenced by urologists. RP group report declines in intimacy and instrumental. AS men worried more about future health and dying than post-RP men. CONCLUSION: Fear of disease progression may be a motivating factor in choosing RP. AS patients adhere to their treatment decision in spite of distress.

Distinct DNA methylation alterations are associated with cribriform architecture and intraductal carcinoma in Gleason pattern 4 prostate tumors.

The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann-Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T-box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer.

Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer.

Background: There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa). Methods: We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort, whereas PLCO data were provided through database of Genotypes and Phenotypes ( dbGaP ). The influence of SNPs of interest on biochemical-free survival was evaluated in a cohort of localized PCa from the International Cancer Genome Consortium (ICGC; n = 130) analyzed with next-generation sequencing. Single- and multi-SNP association studies, as well as haplotype analyses, were performed. All statistical tests were two-sided. Results: Several SNPs in very strong linkage disequilibrium in the KLK 6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (odds ratio [OR] = 3.51-3.64, 95% confidence interval [CI] = 2.01 to 6.36, P = 1.0x10 -5 -8.4x10 -6 ) and validation (OR = 1.89-1.96, 95% CI = 0.99 to 3.71, P = .04-.05) cohorts. The overall test of haplotype association was highly statistically significant in each cohort ( P = 3.5x10 -4 and .006, respectively) and in the three data sets combined ( P = 2.3x10 -5 ). These germline SNPs independently predicted relapse in the ICGC cohort (hazard ratio = 3.15, 95% CI = 1.57 to 6.34, P = .001). Conclusions: Our fine-mapping study has identified novel loci in the KLK 6 region strongly associated with aggressive PCa.

Limitations in Predicting Organ Confined Prostate Cancer in Patients with Gleason Pattern 4 on Biopsy: Implications for Active Surveillance.

PURPOSE: In prostate cancer biopsy Gleason score predicts stage and helps determine active surveillance suitability. Evidence suggests that small incremental differences in the quantitative percent of Gleason pattern 4 on biopsy stratify disease extent, biochemical failure following surgery and eligibility for active surveillance. We explored the overall quantitative percent of Gleason pattern 4 levels and adverse outcomes in patients with low and intermediate risk prostate cancer to whom active surveillance may be offered under expanded criteria. MATERIALS AND METHODS: We analyzed the records of patients with biopsy Gleason score 6 (3 + 3) or 7 (3 + 4) who underwent radical prostatectomy from January 2008 to August 2015. Age, prostate specific antigen, Gleason score, quantitative percent of Gleason pattern 4, overall percent positive cores (percent of prostate cancer) and clinical stage were explored as predictors of nonorgan confined disease and time to failure after radical prostatectomy. RESULTS: In 1,255 patients biopsy Gleason score 7 (3 + 4) was associated with T3 or greater disease at radical prostatectomy in 35.0% compared with Gleason score 6 (3 + 3) in 19.0% (p <0.001). On multivariate analysis for each quantitative percent of Gleason pattern 4 increase there were 2% higher odds of T3 or greater disease (OR 1.02, 95% CI 1.01-1.04, p <0.001). When stratified, patients with Gleason score 7 (3 + 4) only approximated the pT3 rates of Gleason score 6 (3 + 3) when prostate specific antigen was less than 8 ng/ml and the percent of prostate cancer was less than 15%. In those cases the quantitative percent of Gleason pattern 4 had less effect. Time to failure after radical prostatectomy was worse in Gleason score 7 (3 + 4) than 6 (3 + 3) cases. CONCLUSIONS: The quantitative percent of Gleason pattern 4 helps predict advanced disease and Gleason score 7 (3 + 4) is associated with worse outcomes. However, the impact of the quantitative percent of Gleason pattern 4 on adverse pathological and clinical outcomes is best used in combination with prostate specific antigen, age and disease volume since each has a greater impact on predicting nonorgan confined disease. The calculated absolute risk of T3 or greater can be used in shared decision making on prostate cancer treatment by patients and clinicians.

Influence of Metabolic Syndrome on Prostate Cancer Stage, Grade, and Overall Recurrence Risk in Men Undergoing Radical Prostatectomy.

OBJECTIVE: Metabolic syndrome (MetS) is associated with an increased risk of finding prostate cancer overall and high-grade disease on biopsy. This study sought to determine if MetS is associated with adverse final pathology and risk of overall recurrence in men undergoing radical prostatectomy (RP). METHODS: Men undergoing RP (2004-2013) were identified using our prospectively maintained institutional database. MetS was defined by ≥3 of 5 components (obesity, dysglycemia, hypertension, low high-density lipoprotein-cholesterol, and high triglycerides). Multivariable logistic regression models were created for prostate cancer grade and stage on final pathology. Kaplan-Meier and multivariable Cox regression analyses were performed to model overall recurrence, defined by biochemical recurrence (postoperative serum prostate-specific antigen ≥0.2 ng/mL) or use of salvage therapies. RESULTS: Of 1939 men, 439 (22.6%) had MetS. MetS (≥3 vs. 0 components) was associated with an increased odds of Gleason 8-10 disease (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.32-4.67, P = .005) and extraprostatic disease (OR = 1.35, 95% CI = 1.02-1.80, P = .04). Decreased use of nerve-sparing in men with MetS was noted. In unadjusted analyses, MetS was associated with a significantly increased risk of receiving salvage therapy (hazard ratio [HR] = 1.38, 95% CI = 1.04-1.83, P = .03) and a near-significant increased overall recurrence risk (HR = 1.20, 95% CI = 0.94-1.53, P = .15). These associations were attenuated upon adjusting for disease-specific parameters (salvage therapy: HR = 1.03, 95% CI = 0.76-1.40, P = .87; overall recurrence: HR = 0.94, 95% CI = 0.72-1.21, P = .62). CONCLUSION: MetS is associated with an increased odds of extraprostatic and high-grade disease on final RP pathology, which appears to drive an increased risk of needing salvage therapy after RP. However, with more aggressive resection, differences in failure-free outcomes were attenuated, suggesting that men with MetS should not be precluded from RP.

The association of male pattern baldness and risk of cancer and high-grade disease among men presenting for prostate biopsy.

INTRODUCTION: Androgens have been implicated in both male pattern baldness (MPB) and prostate cancer (PCa). We set out to prospectively determine if men with independently assessed MPB are at higher risk for PCa at biopsy and determine if any grade associations exist. METHODS: We prospectively enrolled 394 eligible patients presenting for prostate biopsy and independently determined their MPB pattern using the validated modified Norwood classification system (0: no balding; 1: frontal balding; 2: mild vertex balding; 3: moderate vertex balding; 4: sever vertex balding). Univariate and multivariable models, including Norwood score, age, prostate-specific antigen, and digital rectal examination abnormalities, were calculated for the outcomes of cancer and high-grade disease (Gleason >6). C-statistics analyses of our models were then compared with and without MPB pattern for marginal utility. RESULTS: Norwood patterns were increasingly associated with cancer and high-grade disease with a dose-effect (p for trend <0.001 on univariate and multivariable analyses for cancer and p=0.001 and p=0.0036 for high-grade disease on univariate and multivariable analyses, respectively). On multivariable analyses, trends still held, with all patients exhibiting Norwood scale 3 and 4 at increased risk for cancer. In predicting risk of high-grade disease, only patients with Norwood pattern 4 exhibited an increased risk. CONCLUSIONS: MPB appears to be a strong and independent risk factor for both cancer and high-grade disease for men presenting for prostate biopsy. Ours could be superior to marketed costly genetic tests. Further research is needed to understand the biology behind this observation and to incorporate these findings into clinical decision-making.

A pilot randomized trial of conventional versus advanced pelvic floor exercises to treat urinary incontinence after radical prostatectomy: a study protocol.

BACKGROUND: Radical prostatectomy is the most common and effective treatment for localized prostate cancer. Unfortunately, radical prostatectomy is associated with urinary incontinence and has a significant negative impact on quality of life. Pelvic floor exercises are the most common non-invasive management strategy for urinary incontinence following radical prostatectomy; however, studies provide inconsistent findings regarding their efficacy. One potential reason for sub-optimal efficacy of these interventions is the under-utilization of regional muscles that normally co-activate with the pelvic floor, such as the transverse abdominis, rectus abdominis, and the diaphragm. Two novel approaches to improve urinary continence recovery are 'Pfilates' and 'Hypopressives' that combine traditional pelvic floor exercises with the activation of additional supportive muscles. Our study will compare an advanced pelvic floor exercise training program that includes Pfilates and Hypopressives, to a conventional pelvic floor exercises regimen for the treatment of post-radical prostatectomy urinary incontinence. METHODS/DESIGN: This is a pilot, randomized controlled trial of advanced pelvic floor muscle training versus conventional pelvic floor exercises for men with localized prostate cancer undergoing radical prostatectomy. Eighty-eight men who will be undergoing radical prostatectomy at hospitals in Toronto, Canada will be recruited. Eligible participants must not have undergone androgen deprivation therapy and/or radiation therapy. Participants will be randomized 1:1 to receive 26 weeks of the advanced or conventional pelvic floor exercise programs. Each program will be progressive and have comparable exercise volume. The primary outcomes are related to feasibility for a large, adequately powered randomized controlled trial to determine efficacy for the treatment of urinary incontinence. Feasibility will be assessed via recruitment success, participant retention, outcome capture, intervention adherence, and prevalence of adverse events. Secondary outcomes of intervention efficacy include measures of pelvic floor strength, urinary incontinence, erectile function, and quality of life. Secondary outcome measures will be collected prior to surgery (baseline), and at 2, 6, 12, 26-weeks post-operatively. DISCUSSION: Pfilates and Hypopressives are novel approaches to optimizing urinary function after radical prostatectomy. This trial will provide the foundation of data for future, large-scale trials to definitively describe the effect of these advanced pelvic floor exercise modalities compared to conventional pelvic floor exercise regimes for men with prostate cancer undergoing radical prostatectomy TRIAL REGISTRATION: Clinicalstrials.gov Identifier: NCT02233608.

Real-Time MRI-Guided Focused Ultrasound for Focal Therapy of Locally Confined Low-Risk Prostate Cancer: Feasibility and Preliminary Outcomes.

OBJECTIVE: Focal therapy is an emerging approach to the treatment of localized prostate cancer. The purpose of this study was to report the 6-month follow-up oncologic and functional data of the initial phase 1 trial of patients treated with focal transrectal MRI-guided focused ultrasound in North America. SUBJECTS AND METHODS: Four patients with a prostate-specific antigen (PSA) level of 10 ng/mL or less, tumor classification cT2a or less, and a Gleason score of 6 (3 + 3) were prospectively enrolled in the study and underwent multiparametric MRI and transrectal ultrasound-guided prostate systematic biopsy. Under MRI guidance and real-time monitoring with MR thermography, focused high-frequency ultrasound energy was delivered to ablate the target tissue. The incidence and severity of treatment-related adverse events were recorded along with responses to serial quality-of-life questionnaires for 6 months after treatment. Oncologic outcomes were evaluated with multiparametric MRI and repeat transrectal ultrasound-guided biopsy 6 months after treatment. RESULTS: Four patients with a total of six target lesions were treated and had complications graded Clavien-Dindo I or less. Quality-of-life parameters were similar between baseline and 6-months. All four patients had normal MRI findings in the treated regions (100%), biopsy showed that three patients (75%) were clear of disease in the treated regions, representing complete ablation of five target lesions (83%). All patients had at least one Gleason 6-positive core outside of the treated zone. CONCLUSION: MRI-guided focused ultrasound is a feasible method of noninvasively ablating low-risk prostate cancers with low morbidity. Further investigation and follow-up are warranted in a larger patient series with appropriate statistical analysis of oncologic and functional outcome measures.

Health-related quality of life in robotic versus open radical prostatectomy.

INTRODUCTION: It is unclear whether health-related quality of life (HRQoL) outcomes are superior in robot-assisted radical prostatectomy (RARP) compared to open prostatectomy (ORP). METHODS: We retrospectively analyzed records from men who received ORP or RARP at our institution between January 2009 and December 2012. Patients completed a demographics questionnaire and the Patient-Oriented Prostate Utility Scale (PORPUS), a validated disease-specific HRQoL instrument prior to surgery and every 3 months up to 15 months after surgery. RESULTS: In total, 974 men met the inclusion criteria (643 ORP and 331 RARP patients). At baseline, RARP patients were significantly younger (p < 0.001), had lower body mass index (BMI) (p < 0.001), lower preoperative prostate-specific antigen (PSA) (p < 0.001), fewer comorbidities (p < 0.004), and higher baseline PORPUS scores (p = 0.024). On follow-up, unadjusted PORPUS scores were significantly higher in the RARP group at each point. On multivariable analysis adjusting for age, ORP versus RARP procedure, Gleason score, BMI, first PSA, comorbidity, ethnicity, and baseline PORPUS scores, PORPUS score was higher for the RARP group at 3 months (p = 0.038) and 9 months (p = 0.037), but not at 6, 12, and 15 months (p = 0.014). No difference met pre-defined thresholds of clinical significant. CONCLUSIONS: Though unadjusted HRQoL outcomes appeared improved with RARP compared to ORP differences, adjusted differences were seen at only 2 of 5 postoperative time points, and did not meet pre-defined thresholds of clinical significance. Further randomized trials are needed to assess whether one treatment option provides consistently better HRQoL outcomes.

MRI-guided biopsies and minimally invasive therapy for prostate cancer.

Recent advances in multiparametric magnetic resonance imaging (mp-MRI) have led to a paradigm shift in the diagnosis and management of prostate cancer (PCa). Its sensitivity in detecting clinically significant cancer and the ability to localize the tumor within the prostate gland has opened up discussion on targeted diagnosis and therapy in PCa. Use of mp-MRI in conjunction with prostate-specific antigen followed by targeted biopsy allows for a better diagnostic pathway than transrectal ultrasound (TRUS) biopsy and improves the diagnosis of PCa. Improved detection of PCa by mp-MRI has also opened up opportunities for focal therapy within the organ while reducing the incidence of side-effects associated with the radical treatment methods for PCa. This review discusses the evidence and techniques for in-bore MRI-guided prostate biopsy and provides an update on the status of MRI-guided targeted focal therapy in PCa.

In-bore MRI interventions: current status and future applications.

PURPOSE OF REVIEW: This review discusses the feasibility, recent advances and current status of in-bore MRI-guided interventional techniques for diagnosis and treatment of focal prostate cancer (PCa) and also explores the future applications, highlighting the emerging strategies for the treatment of PCa. RECENT FINDINGS: Multiparametric MRI has opened up opportunities for diagnosis and targeted therapeutics to the site of disease within the organ wherein minimizing the incidence of treatment-related toxicity of whole gland therapy. MRI-guided targeted biopsy has a higher detection rate for significant cancer and lower rate of detection of insignificant cancer. In comparison to ultrasound-guided focal therapy, in-bore treatment provides the advantage of real time thermal monitoring during treatment and assessment of treatment coverage by an enhanced scan immediately post-treatment. Preliminary results of ongoing phase I and II in-bore focal PCa treatment trials via transperineal, transrectal and transurethral routes, using different energy modalities for the ablation, have shown promising results. SUMMARY: Advances in multiparametric-MRI has opened up opportunities for in-bore targeted focal treatment of PCa in the correctly selected patient.

Elastic registration of prostate MR images based on estimation of deformation states.

Magnetic resonance imaging (MRI) is being used increasingly for image-guided targeted biopsy and focal therapy of prostate cancer. In this paper, a combined rigid and deformable registration technique is proposed to register pre-treatment diagnostic 3T magnetic resonance (MR) images of the prostate, with the identified target tumor(s), to intra-treatment 1.5T MR images. The pre-treatment T2-weighted MR images were acquired with patients in a supine position using an endorectal coil in a 3T scanner, while the intra-treatment T2-weighted MR images were acquired in a 1.5T scanner before insertion of the needle with patients in the semi-lithotomy position. Both the rigid and deformable registration algorithms employ an intensity-based distance metric defined based on the modality independent neighborhood descriptors (MIND) between images. The optimization routine for estimating the rigid transformation parameters is initialized using four pairs of manually selected approximate corresponding points on the boundaries of the prostate. In this paper, the problem of deformable image registration is approached from the perspective of state estimation for dynamical systems. The registration algorithm employs a rather generic dynamic linear elastic model of the tissue deformation discretized by the finite element method (FEM). We use the model in a classical state estimation framework to estimate the deformation of the prostate based on the distance metric between pre- and intra-treatment images. Our deformable registration results using 17 sets of prostate MR images showed that the proposed method yielded a target registration error (TRE) of 1.87 ± 0.94 mm,2.03 ± 0.94 mm, and 1.70 ± 0.93 mm for the whole gland (WG), central gland (CG), and peripheral zone (PZ), respectively, using 76 manually-identified fiducial points. This was an improvement over the 2.67 ± 1.31 mm, 2.95 ± 1.43 mm, and 2.34 ± 1.11 mm, respectively for the WG, CG, and PZ after rigid registration alone. Dice similarity coefficients (DSC) in the WG, CG and PZ were 88.2 ± 5.3, 85.6 ± 7.6 and 68.7 ± 6.9 percent, respectively. Furthermore, the mean absolute distances (MAD) between surfaces was 1.26 ± 0.56 mm and 1.27 ± 0.55 mm in the WG and CG, after deformable registration. These results indicate that the proposed registration technique has sufficient accuracy for localizing prostate tumors in MRI-guided targeted biopsy or focal therapy of clinically localized prostate cancer.

Mechatronic system for in-bore MRI-guided insertion of needles to the prostate: An in vivo needle guidance accuracy study.

BACKGROUND: To present our experiences in initial clinical evaluation of a novel mechatronic system for in-bore guidance of needles to the prostate for MRI-guided prostate interventions in 10 patients. We report accuracy of this device in the context of focal laser ablation therapy for localized prostate cancer. METHODS: An MRI-compatible needle guidance device was developed for transperineal prostate interventions. Ten patients underwent MRI-guided focal laser ablation therapy with device-mediated laser fiber delivery. We recorded needle guidance error and needle delivery time. RESULTS: A total of 37 needle insertions were evaluated. Median needle guidance error was 3.5 mm (interquartile range, 2.1-5.4 mm), and median needle delivery time was 9 min (interquartile range, 6.5-12 min). CONCLUSION: This system provides a reliable method of accurately aligning needle guides for in-bore transperineal needle delivery to the prostate.