Multiparametric magnetic resonance imaging for prostate cancer—a comparative study including radical prostatectomy specimens

Purpose

To evaluate the diagnostic and staging ability of multiparametric MRI (mpMRI) compared to radical prostatectomy (RP) specimens after dissemination of this technology to several centres. mpMRI is an evolving technique aiming to improve upon the diagnostic sensitivity of prostate biopsy for the diagnosis of prostate cancer. Differences in interpretation, expertise and application of mpMRI are responsible for the range of reported results.

Methods

This retrospective clinical study was conducted with consecutive patients through an electronic database of tertiary hospitals and adjacent private urology practices in Australia. Patients having undergone RP were assessed for the presence of a pre-operative mpMRI performed between 2013 and 2015 which was evaluated against the reference standard of the RP whole-mount specimen. MRI reports were evaluated using the Prostate Imaging Reporting and Data System (PI-RADS).

Results

In our cohort of 152 patients, the sensitivity and specificity of mpMRI (PI-RADS ≥ 4) for prostate cancer (Gleason ≥ 4 + 3) detection were 83 and 47%, respectively. For the identification of extraprostatic disease, the sensitivity and specificity were 29 and 94%, respectively.

Conclusion

These results represent a ‘real-world’ approach to mpMRI and appear comparable to other single-centre studies. MRI staging information should be interpreted in context with other risk factors for extraprostatic disease. mpMRI has a useful role as an adjunct for prostate cancer diagnosis and directing management towards improving patient outcomes.

     

Does neoadjuvant hormone therapy for early prostate cancer affect cognition? Results from a pilot study

OBJECTIVE: To examine, in a prospective study, the influence that temporary reversible medical castration for localized prostate cancer has on cognition, by assessing whether temporary 3-5 month treatment with a luteinizing-hormone releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long-term affect on cognitive function. PATIENTS, SUBJECTS AND METHODS: Thirty-two patients with localized prostate cancer had cognitive assessments at baseline (T1) before the start of drug treatment, at 3 months (T2) or on completing drug treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no prostate cancer (controls subjects) completed the cognitive tests at the same times. In addition, psychological functioning and quality of life were assessed at the same times, together with serum free and bound testosterone, beta-oestradiol and sex hormone-binding globulin levels. RESULTS: There was a significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%) patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients (nine of 15) who had a change in performance declined on tasks of spatial memory and ability. At T3 there was significant cognitive decline in 11 (34%) patients and five (28%) control subjects (odds ratio 1.37, P = 0.631). CONCLUSION: This pilot study suggests that short-term LHRH therapy for early-stage prostate cancer has modest short-term consequences on men's cognitive functioning; a larger prospective study is warranted.     

Prostate-specific antigen vs. magnetic resonance imaging parameters for assessing oncological outcomes after high intensity–focused ultrasound focal therapy for localized prostate cancer

Introduction

Focal therapy for localized prostate cancer has the potential for oncological control without the side effects of radical therapies. However, there is currently no validated method for monitoring treatment success. We assessed the diagnostic performance of prostate-specific antigen (PSA) parameters and MRI compared to histological outcomes following focal therapy.

Cure following gene therapy for recurrent glioblastoma multiforme?

Summary  We report a patient with glioblastoma multiforme who is alive and disease-free 13 years following aggressive treatment with multiple surgeries, radiotherapy, chemotherapy, and gene therapy. Correspondence: Mark Bernstein, MD, FRCSC, Division of Neurosurgery, University of Toronto, Toronto Western Hospital, 399 Bathurst Street, 4 West Wing, M5T 2S8 Toronto, Ontario, Canada.     

Does tadalafil prevent erectile dysfunction in patients undergoing radiation therapy for prostate cancer？

Arecently published paper addressed the interesting topic of prevention of erectile dysfunction （ED） with tadalafil, a pbosphodiesterase-type 5 inhibitor （PDE5i） in patients undergoing radiation therapy for localized prostate cancer. Tadalafil 5 mg or placebo was administered once-daily for 24 weeks in patients undergoing external-beam radiotherapy （EBRT） or brachytherapy （BT） for prostate cancer. This randomized trial did not show superior efficacy of the active drug compared with placebo 4-6 weeks after stopping the study drug. Furthermore, patients younger than 65 years did not respond significantlybetter than older patients.     

Does adding local salvage ablation therapy provide survival advantage for patients with locally recurrent prostate cancer following radiotherapy?: Whole gland salvage ablation post-radiation failure in prostate cancer

IntroductionSome men who experience prostate cancer recurrence post-radiotherapy may be candidates for local salvage therapy, avoiding and delaying systemic treatments. Our aim was to assess the impact of clinical outcomes of adding salvage local treatment in prostate cancer patients who have failed radiation therapy.MethodsFollowing radiation biochemical failure, salvage transperineal cryotherapy (sCT, n=186), transrectal high intensity focused ultrasound ablation (sHIFU, n=113), or no salvage treatment (NST, identified from the pan-Canadian Prostate Cancer Risk Stratification [ProCaRS] database, n=982) were compared with propensity-score matching. Primary endpoints were cancer-specific survival (CSS) and overall survival (OS).ResultsMedian followup was 11.6, 25.1, and 14.3 years following NST, sCT, and sHIFU, respectively. Two propensity score-matched analyses were performed: 1) 196 NST vs. 98 sCT; and 2) 177 NST vs. 59 sHIFU. In the first comparison, there were 78 deaths and 49 prostate cancer deaths for NST vs. 80 deaths and 24 prostate cancer deaths for sCT. There were significant benefits in CSS (p<0.001) and OS (p<0.001) favoring sCT. In the second comparison, there were 52 deaths (31 from prostate cancer) for NST vs. 18 deaths (nine from prostate cancer) for sHIFU. There were no significant differences in CSS or OS possibility attributed to reduced sample size and shorter followup of sHIFU cohort.ConclusionsIn select men with recurrent prostate cancer post-radiation, further local treatment may lead to benefits in CSS. These hypothesis-generating findings should ideally be validated in a prospective clinical trial setting.     

Impact of preoperative immunonutrition on morbidity following cystectomy for bladder cancer: a case–control pilot study

Purpose

To compare postoperative complications in patients with or without preoperative immunonutrition before cystectomy.

Methods

A prospective, multicenter, pilot, case–control study was conducted during 6 months. Patients with 7-day preoperative immunonutrition were prospectively included and compared with a retrospective, matched control group without immunonutrition. Early complication rates and the length of hospital stay were analyzed. The bilateral type I error was <0.05; the power was 90 %. Thirty patients in each group were required.

Results

Thirty patients were included in each group, on a comparable basis. In the immunonutrition group, fewer postoperative complications (40 vs. 76.7 %; p = 0.008), less paralytic ileus at D7 (6.6 vs. 33.3 %; p = 0.02), fewer infections (23.3 vs. 60 %; p = 0.008), and in particular less pyelonephritis (16.7 vs. 46.7 %; p = 0.03) occurred. Clavien’s grades for complications were higher in the control group (p = 0.04). Mortality, pulmonary embolism, anastomotic fistulae, and wound dehiscence were similar between two groups. The length of stay was reduced by 3 days in the immunonutrition group.

Conclusions

In this pilot case–control study, immunonutrition is associated with a decrease in postoperative complications, urinary tract infections, Clavien’s grade for complications, and paralytic ileus in patients undergoing cystectomy for bladder cancer. Prospective randomized placebo control studies are needed to confirm these promising results.     

Multiparametric magnetic resonance imaging–targeted biopsy for the detection of prostate cancer in patients with prior negative biopsy results

PurposeWe aimed to determine the performance of multiparametric magnetic resonance imaging (mpMRI) in the detection of prostate cancer (PCa) in patients with prior negative transrectal ultrasound–guided prostate biopsy (TRUS-B) results.Materials and methodsBetween 2010 and 2013, 2,416 men underwent TRUS-B or an mpMRI or both at Vancouver General Hospital. Among these, 283 men had persistent suspicion of PCa despite prior negative TRUS-B finding. An MRI was obtained in 112, and a lesion (prostate imaging reporting and data system score ≥3) was identified in 88 cases (78%). A subsequent combined MRI-targeted and standard template biopsy was performed in 86 cases. A matching cohort of 86 patients was selected using a one-nearest neighbor method without replacement. The end points were the rate of diagnosis of PCa and significant PCa (sPCa) (Gleason>6, or>2 cores, or>50% of any core).ResultsMRI-targeted TRUS-B detected PCa and sPCa in 36 (41.9%) and 30 (34.9%) men when compared with 19 (22.1%) and 14 (16.3%), respectively, men without mpMRI (P = 0.005 for both). In 9 cases (10.4%), MRI-targeted TRUS-B detected sPCa that was missed on standard cores. sPCa was present in 6 cases (6.9%) on standard cores but not the targeted cores. Multivariate analysis revealed that prostate imaging reporting and data system score and prostate-specific antigen density>0.15 ng/ml² were statistically significant predictors of significant cancer detection (odds ratio = 14.93, P<0.001 and odds ratio = 6.19, P = 0.02, respectively).ConclusionIn patients with prior negative TRUS-B finding, MRI-targeted TRUS-B improves the detection rate of all PCa and sPCa.     

Magnetic resonance imaging–targeted vs. conventional transrectal ultrasound–guided prostate biopsy: Single-institution,matched cohort comparison

ObjectivesTo compare magnetic resonance imaging–targeted biopsy (MRITB) and conventional transrectal ultrasound–guided biopsy (TRUSGB) in the detection of prostate cancer (PCa) at our institution.MethodsOur prospective registry of patients undergoing prostate MRITB from December 2010 to July 2013 was analyzed. Patients were matched one-to-one to patients who underwent TRUSGB based on the following characteristics: age, prostate-specific antigen level, prostate volume, race, family history of PCa, initial digital rectal examination (DRE), prior use of 5-alpha reductase inhibitor, and prior diagnosis of PCa. MRITB was performed using a TargetScan system with the patient under general anesthesia. Magnetic resonance imaging suspicious regions (MSRs) were targeted with cognitive registration, and a full TargetScan template biopsy (TSTB) was also performed.ResultsIn total, 34 MRITB patients were matched individually to 34 TRUSGB patients. As compared with TRUSGB, patients who underwent MRITB had a greater overall rate of PCa detection (76% vs. 56%, P = 0.12) and a significantly higher number with Gleason score≥7 (41% vs. 15%, P = 0.03), whereas the rates of Gleason score 6 PCa detection were similar between MRITB and TRUSGB (35% vs. 41%, P = 0.80). As compared with the TSTB, magnetic resonance imaging suspicious regions–directed biopsies during MRITB had a significantly higher overall PCa detection (54% vs. 24%, P<0.01) and Gleason score≥7 PCa detection (25% vs. 8%, P<0.01). When compared with TSTB, TRUSGB had similar detection rates for benign prostate tissue (76% vs. 79%, P = 0.64), Gleason score 6 PCa (16% vs. 14%, P = 0.49), and Gleason score ≥7 PCa detection (8% vs. 7%, P = 1.0).ConclusionsCognitive registration MRITB significantly improves the detection of Gleason score≥7 PCa as compared with conventional TRUSGB.     

Magnetic resonance imaging study determining cord level and occupancy at thoracolumbar junction in achondroplasia �C A prospective study

Background:

Thoracolumbar (TL) stenosis in achondroplasia is frequently reported, and becomes symptomatic in adulthood. Hence we conducted a prospective study to determine cord level and occupancy at TL junction in symptomatic or asymptomatic achondroplasis patients in comparision to normal population by magnetic resonance imaging (MRI).

Materials and Methods:

Cord level with its occupancy rate and TL kyphosis were measured on MRI and standing radiogram, respectively. We prospectively studied MRI of TL spine in 19 patients (7 males and 12 females) with achondroplasia. All the subjects were randomly selected from our outpatient clinic and divided into two groups: symptomatic and asymptomatic group. Symptomatic group had at least two of the following symptoms: back pain with spasticity and walking difficulty, radicular pain in upper thigh or girdle pain, tingling and numbness in the lower limbs, visible deformity at TL spine and brisk reflexes in lower extremities. Asymptomatic group was selected from those patients who visited in outpatient clinic for consultation of limb lengthening. The third group was taken as control that comprised 11 nonachondroplasia otherwise normal patients (8 males and 3 females) who presented to our outpatient clinic for back pain.

Results:

Results showed spinal cord level was higher in achondroplasia than nonachondroplasia (P=0.003); however, no difference in cord level between symptomatic and asymptomatic group (P=0.568). Comparing cord occupancy, no difference found among all three groups (P=0.20). Kyphosis was increasing from nonachondroplasia, asymptomatic and symptomatic patient groups (P<0.001). Average age was 22.4±14.2, 11.9±6.5, and 36.2±13.2 years in symptomatic, asymptomatic, and nonachondroplasia groups, respectively (P<0.001).

Conclusion:

Our results indicated high level of spinal cord in achondroplasia patients compared to nonachondroplasia individuals. High prevalence of neurological symptoms at TL level in such patients can be associated with high cord level and developing progressive kyphosis at TL level along with degenerative process.     

Focal therapy for prostate cancer: Fact or fiction?

Prostate cancer is the commonest male cancer diagnosed in men in the UK, and the treatment of organ confined prostate cancer is a subject of much debate. Focal therapy for prostate cancer intends to treat the cancer within the prostate, whilst sparing the majority of the benign prostate tissue. In addition, the intention is to avoid treatment effects in the surrounding structures, the damage of which leads to the side effects commonly associated with radical whole gland therapies. This relies on accurate localization of the prostate cancer by biopsy and imaging followed by treatment using a modality capable of delivery to a focal area within the prostate. Focal therapy lies between the current extremes of radical whole gland treatment and active surveillance. There have been many articles reviewing the concept of focal therapy for organ confined prostate cancer, but with a paucity of data available for analysis. This is being addressed with an increase in the published data on focal therapy, using a number of different modalities. In this review, we address the question of whether the data currently published does in fact support the further development of the focal therapy approach, or whether it is a concept best relegated to the realms of fiction.     

The hypothalamic–pituitary–gonadal axis and prostate cancer: implications for androgen deprivation therapy

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may play important roles in prostate cancer (PCa) progression. Specifically, LH expression in PCa tissues has been associated with metastatic disease with a poor prognosis, while FSH has been shown to stimulate prostate cell growth in hormone-refractory PCa cell lines. Gonadotropin-realizing hormone (GnRH) analogues are common agents used for achieving androgen deprivation in the treatment for PCa. GnRH analogues include LH-releasing hormone (LHRH) agonists and GnRH antagonists, both of which exhibit distinct mechanisms of action that may be crucial in terms of their overall clinical efficacy. LHRH agonists are typically used as the primary therapy for most patients and function via a negative-feedback mechanism. This mechanism involves an initial surge in testosterone levels, which may worsen clinical symptoms of PCa. GnRH antagonists provide rapid and consistent hormonal suppression without the initial surge in testosterone levels associated with LHRH agonists, thus representing an important therapeutic alternative for patients with PCa. The concentrations of testosterone and dihydrotestosterone are significantly reduced after treatment with both LHRH agonists and GnRH antagonists. This reduction in testosterone concentrations to castrate levels results in significant, rapid, and consistent reductions in prostatic-specific antigen, a key biomarker for PCa. Evidence suggests that careful maintenance of testosterone levels during androgen deprivation therapy provides a clinical benefit to patients with PCa, emphasizing the need for constant monitoring of testosterone concentrations throughout the course of therapy.