Fouad Aoun

Clinical impact of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach

To assess the impact of a novel molecular imaging technique, 68Ga‐(HBED‐CC)‐prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate‐specific antigen (PSA) after treatment with curative intent.

MRI-Targeted Biopsies versus Systematic Transrectal Ultrasound Guided Biopsies for the Diagnosis of Localized Prostate Cancer in Biopsy Naïve Men

Introduction. To compare, in the same cohort of men, the detection of clinically significant disease in standard (STD) cores versus multiparametric magnetic resonance imaging (mpMRI) targeted (TAR) cores. Material and Methods. A prospective study was conducted on 129 biopsy naïve men with clinical suspicion of prostate cancer. These patients underwent prebiopsy mpMRI with STD systematic biopsies and TAR biopsies when lesions were found. The agreement between the TAR and the STD protocols was measured using Cohens kappa coefficient. Results. Cancer detection rate of MRI-targeted biopsy was 62.7%. TAR protocol demonstrated higher detection rate of clinically significant disease compared to STD protocol. The proportion of cores positive for clinically significant cancer in TAR cores was 28.9% versus 9.8% for STD cores (P < 0.001). The proportion of men with clinically significant cancer and the proportion of men with Gleason score 7 were higher with the TAR protocol than with the STD protocol (P = 0.003; P = 0.0008, resp.). Conclusion. mpMRI improved clinically significant prostate cancer detection rate compared to STD protocol alone with less tissue sampling and higher Gleason score. Further development in imaging as well as multicentre studies using the START recommendation is needed to elucidate the role of mpMRI targeted biopsy in the management of prostate cancer.

A prospective clinical trial of HIFU hemiablation for clinically localized prostate cancer

Background:Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer aimed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control. We report the mid-term oncological and functional results of primary hemiablation high-intensity focused ultrasound (HIFU) in a prospective cohort of patients.Methods:Over 8 years, hemiablation HIFU was primarily performed in 50 selected patients with biopsy-proven clinically localized unilateral, low–intermediate risk prostate cancer in complete concordance with the prostate cancer lesions identified by magnetic resonance imaging with precise loci matching on multimodal approach. Post-treatment follow-up included regular serial PSA measurements. Biochemical recurrence was reported using Stuttgart and Phoenix criteria. The latter was used as a threshold to offer whole-gland biopsies.Results:Complete follow-up was available for all patients and the median follow-up was 39.5 months (range: 6–94). Mean nadir PSA value was 1.6 ng ml−1, which represents 72% reduction compared with initial PSA pre-treatment value (P<0.001). Median time to achieve PSA nadir was 3 months. Biochemical recurrence, according to Phoenix and Stuttgart definition, occurred in 28 and 36% of patients, respectively. The 5-year actuarial metastases-free survival, cancer-specific survival and overall survival rates were 93, 100 and 87%, respectively. Out of the eight patients undergoing biopsy, six patients had a positive biopsy for cancer occurring in the untreated contralateral (n=3) or treated ipsilateral lobe (n=1) or bilaterally (n=2). A Clavien–Dindo grade 3b complication occurred in two patients. Complete continence (no pads) and erection sufficient for intercourse were documented in 94 or 80% of patients, respectively.Conclusion:Hemiablation HIFU therapy, delivered with intention to treat, for carefully selected patients affords mid-term promising functional and oncological outcomes. The effectiveness of this technique should be now compared with whole-gland radical therapy.

Primary Zonal High Intensity Focused Ultrasound for Prostate Cancer: Results of a Prospective Phase IIa Feasibility Study

Aims. In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. Methods. Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5%) was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. Results. A total of 557 men have decided to freeze their semen before cancer treatment. Seminoma was diagnosed in 283 men (54.1%) and nonseminomatous germ cell tumors in 240 men (45.9%). 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. Conclusion. The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.

A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer

To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept.

Single High Intensity Focused Ultrasound Session as a Whole Gland Primary Treatment for Clinically Localized Prostate Cancer: 10-Year Outcomes

Objectives. To assess the treatment outcomes of a single session of whole gland high intensity focused ultrasound (HIFU) for patients with localized prostate cancer (PCa). Methods. Response rates were defined using the Stuttgart and Phoenix criteria. Complications were graded according to the Clavien score. Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients experienced biochemical recurrence for Phoenix and Stuttgart definition, respectively. The 5- and 10-year actuarial biochemical recurrence free survival rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%, respectively. Preoperative high risk category, Gleason score, preoperative PSA, and postoperative nadir PSA were independent predictors of oncological failure. 24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and 18.2% had acute urinary retention. A grade 3b complication occurred in 27 patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate was 30.8%. Conclusion. Single session HIFU can be alternative therapy for patients with low risk PCa. Patients with intermediate risk should be informed about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU performed very poorly in high risk patients.

3D versus 2D Systematic Transrectal Ultrasound-Guided Prostate Biopsy: Higher Cancer Detection Rate in Clinical Practice.

Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 consecutive patients with no prior history of prostate cancer who underwent an initial prostate biopsy in daily practice due to an abnormal PSA and/or DRE using, respectively, the classical 2D and the new 3D systems. All the biopsies were done by a single experienced operator using the same standardized protocol. Results. There was no significant difference in terms of age, total PSA, or prostate volume between the two groups. However, cancer detection rate was significantly higher using the 3D versus the 2D system, 50% versus 34% (P < 0.05). There was no statistically significant difference while comparing the 2 groups in term of nonsignificant cancer detection. Conclusion. There is reasonable evidence demonstrating the superiority of the 3D-guided biopsies in detecting prostate cancers that would have been missed using the 2D extended protocol.

Critical Analysis of Early Recurrence after Laparoscopic Radical Cystectomy in a Large Cohort by the ESUT.

PURPOSE We analyze patients with early progression after laparoscopic radical cystectomy in a large cohort by the ESUT (European Association of Urology Section of Uro-Technology). More specifically we focus on patients with favorable pathology (pT2 N0 R0 or less) who experienced an unexpected recurrence and analyze possible causes for such early recurrence, discussing the surgical technique including pneumoperitoneum. MATERIALS AND METHODS Since 2000 the ESUT has been constructing a large, multicenter, prospective database of patients undergoing laparoscopic radical cystectomy. All procedures were performed via a standard laparoscopic approach without robotic assistance. We specifically analyzed patients with favorable pathological characteristics, in particular pT2 N0 R0 or less, and evaluated those with progression despite these favorable characteristics. Univariate and multivariate logistic regression was performed to evaluate risk factors for early recurrence. RESULTS A total of 627 patients were available for final analysis with a median followup of 46 months (mean 57). Of these patients 311 had favorable pathological characteristics of pT2 N0 R0 or less. During followup 27 (8.7%) patients experienced disease progression during the first 24 months. Surgical negligence was found in only 1 case. Most of these patients with early recurrence had progression to high tumor volume disseminated metastatic disease. On multivariate logistic regression tumor stage was the only factor significantly associated with early recurrence (p=0.027). CONCLUSIONS We report early unexpected recurrences after laparoscopic radical cystectomy in nearly 5% of our entire cohort, all in patients with favorable pathological characteristics (pT2 N0 R0 or less). Pneumoperitoneum may have had a role in the development of these relapses. Specifically designed studies are necessary to investigate the possible role of pneumoperitoneum in urothelial cancer recurrence.

Lower urinary tract dysfunction after nerve-sparing radical hysterectomy

Introduction and hypothesisThe aim of this review is to provide a comprehensive overview of the current role of nerve-sparing radical hysterectomy (NSRH) in reducing the incidence of postoperative lower urinary tract dysfunction (LUTD) and in improving quality of life.MethodsA detailed online search was performed using the following keywords: nerve sparing, radical hysterectomy, cervical cancer, and all these terms in combination with urinary dysfunction or bladder dysfunction in order to analyze the effect of NSRH on urinary functional outcomes. Articles retrieved were analyzed and assigned a level of evidence (LE) according to the criteria of the Centre for Evidence-Based Medicine in Oxford, UK.ResultsOur review highlights the heterogeneity of conducting and reporting studies in the literature. Autonomic pelvic nerve injuries during the procedure are thought to be the major cause of LUTD. The amount of LUTD depends upon the extent and type of nerve injury. Anatomically based surgical techniques are developed to avoid nerve injury without compromising oncological control. All studies comparing NSRH to standard RH yielded promising results with respect to postoperative LUTD. A recent meta-analysis showed similar cancer control rates between the two techniques. However, controversies remain about the ideal surgical approach for nerve sparing and there is no consensus as to the level and landmarks of dissection to preserve the maximal amount of nerves without compromising oncological outcomes.ConclusionsAvailable evidence suggests that NSRH is safe and associated with lower incidence of LUTD. However, there is no standardized technique for NSRH and controversies remain about its oncological safety. Long-term oncological data from multicenter surgical trials are needed as well as a universally accepted standard to report studies on NSRH.

Checkpoint inhibitors in bladder and renal cancers: Results and perspectives

The field of immunotherapy in urinary malignancy is expanding in several directions and checkpoint inhibitors are leading the way. The aim of this report is to highlight the efficacy and safety profile of the two classes of molecules, anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death receptor-1/programmed death ligand type 1, that are under investigation and represent potential candidates to be used in the near future for the management of bladder and renal cell cancer. The preliminary results as well as the future perspectives of this novel immunotherapy are analyzed. Novel immune checkpoint targets are reviewed as well.