Targeted microwave ablation for prostate cancer (FOSTINE1b): a prospective 'ablate-and-resect' study.

OBJECTIVE: To assess histopathological outcomes, as well as feasibility and safety of targeted microwave ablation (TMA) via the Trinity® system (KOELIS, La Tronche, France). PATIENTS AND METHODS: Prospective, single-institution, interventional Phase IIa study with an 'ablate-and-resect' design. In all, 11 patients diagnosed with localised prostate cancer (PCa) underwent TMA via the Trinity system under conscious sedation in an outpatient setting using a single transrectal TATO® 18-G antenna with different treatment regimens. Magnetic resonance imaging (MRI) and robot-assisted radical prostatectomy (RARP) were conducted at 7 days and 1 month after TMA, respectively. Nine patients received RARP, and two patients chose to withdraw their consent following TMA. These men chose an active surveillance protocol upon confirmation of a low-risk prostate cancer diagnosis. Functional outcomes and adverse events were evaluated at baseline and follow-up visits using validated questionnaires. Prostate volumetry and confirmation of necrosis were carried out through MRI and whole-mount histopathological examination. RESULTS: The TMA was successfully executed, and all patients were discharged on the same day. No severe adverse events (Common Terminology Criteria for Adverse Events Grade ≥3) were reported at the 7-day and 1-month follow-up visits. Additionally, no declines were observed in urinary, sexual and ejaculation functional outcomes. T1-weighted MRI revealed clear and well-defined ablation zones. The RARP was executed without difficulty, particularly during the dissection of the posterior plane. As a result, no intraoperative complications were encountered. Histopathological assessment on surgical specimens confirmed the absence of viable cells, indicating complete necrosis of the ablative zone if a power intensity >10 W was used during TMA. Ablation zone volumetry revealed no notable distinctions between the three-dimensional segmentation of the virtual ablation zone at TMA (median volume: 2 mL) and MRI (median volume: 1.923 mL). Conversely, a significant reduction was noted in the surgical specimen (median volume: 0.221 mL). CONCLUSIONS: Targeted microwave ablation via the Trinity system for localised PCa treatment proves to be a secure and feasible procedure, with complete necrosis evidence within the ablation zone on surgical specimens.

Salvage high-intensity focused ultrasound versus salvage radical prostatectomy for radiation-recurrent prostate cancer: a comparative study of oncological, functional, and toxicity outcomes.

PURPOSE: To compare oncological, functional, and toxicity outcomes of patients with radiation-recurrent prostate cancer (PCa) after external beam radiation therapy (EBRT) or brachytherapy (BT) treated with salvage high-intensity focused ultrasound (S-HIFU) or salvage radical prostatectomy (S-RP). METHODS: This retrospective study compared 52 patients with radiation-recurrent PCa after EBRT or BT treated with S-HIFU (n = 27) or S-RP (n = 25) between 1998 and 2016. We estimated overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) at 5 years. Incontinence after local salvage therapy (LST) was scored according to the number of pads used per day. Complications were graded according to the Clavien-Dindo classification. RESULTS: Both groups were similar for pre-LST tumor features, however, no S-HIFU patients received BT and S-RP patients were younger and healthier. Median follow-up was 45 months for S-HIFU and 43 months for S-RP. No significant differences were found in estimated 5-year OS (80.9% vs. 61.9%, p = 0.24), 5-year CSS (84.0% vs. 74.0%, p = 0.36), and 5-year MFS (60.3% vs. 55.2%, p = 0.55) for S-HIFU vs. S-RP, respectively. We observed a significant difference in pad-dependent status at 12 months (22.2% vs. 56.0%, p = 0.01) and in the number of Clavien ≥ III complications [9 (7/27 patients) vs. 16 (12/25 patients), p = 0.027] in favor of S-HIFU vs. S-RP, respectively. CONCLUSION: S-HIFU and S-RP could both be considered valuable LST options for patients with radiation-recurrent nonmetastatic PCa with sufficient life expectancy. S-RP is associated with more pad-dependent patients at 12 months.

Cartography-based quality control of prostate cancer care: a necessary ground to targeted focal therapy.

PURPOSE OF REVIEW: We summarize the evidence on accurate target definition, precise imaging, and guiding systems that are a necessary ground to targeted focal therapy. RECENT FINDINGS: Accurate target detection is based on the ability of imaging to locate and characterize precisely the tumor burden and differentiation inside the prostate. There is a clear correlation with the multiparametric MRI (mpMRI) images and the morphologic attributes of the tumor. Limitations stem from the heterogeneity and the multifocality of prostate cancer. Some prostate cancers are MRI-negative tumors. Safety margins should also be elaborated based on the tumor grade and burden. PET prostate specific membrane antigen is another promising technology yielding same results as multiparametric MRI for primary detection of prostate cancer, but PET/MRI imaging is promising. Perfect guiding requires sophisticated software with good quality control to track the needle inside the prostate and to record the position allowing recall when second look biopsy, active surveillance, or targeted focal therapy are required. SUMMARY: The multimodal fusion cartography model proves effective and necessary to fulfill preoperative and postoperative requirements for targeted focal therapy.

Salvage Hemiablation High Intensity Focused Ultrasound for unilateral radio-recurrent prostate cancer.

OBJECTIVE: To report the oncological and functional outcomes of salvage hemiablation high-intensity focused ultrasound (HIFU) in patients with unilateral radio-recurrent prostate cancer. PATIENTS AND METHODS: Patients with biochemical recurrence (BCR) after primary radiation therapy and evidence of unilateral organ confined recurrence based on a complete match between mpMRI and MRI targeted biopsies were included. Patients with distant metastasis were excluded. Patients were followed with serial serum PSA determinations. BCR were defined using the Phoenix criteria. Complications were graded according to the Clavien score. IIEF-5 questionnaire was used to assess erectile dysfunction. Urinary incontinence was reported using physician reported rates. RESULTS: A total of 10 consecutive patients (median age: 71 years, IQR: 69-76) were prospectively enrolled. The median pre-treatment PSA and post-treatment PSA nadir were 3.1ng/mL (IQR: 1.54-8.59) and 1.52ng/mL (IQR: 0.76-2.2), respectively. At a median follow-up of 41.5 (IQR: 18-58) months, 50% of patients experience BCR. BCR free-survival rates at 24 and 36 months were 75% (CI95%: 31-93) and 60% (CI95%: 20-85), respectively. Urinary in continence grade II occurred in two patients and the remaining patients were pad-free. One patient developed de novo erectile dysfunction requiring PDE5I. The erectile function scores decreased from a mean of 10.1 to 8.7. CONCLUSION: Hemiablation HIFU is an alternative to whole gland therapy in patients with unilateral radio- recurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves functional outcomes. LEVEL OF EVIDENCE: 3.

Patterns and predictors of recurrence after open radical cystectomy for bladder cancer: a comprehensive review of the literature.

PURPOSE: To review the currently available literature reporting the patterns of recurrence and their predictive factors after open radical cystectomy (RC) for bladder cancer. METHODS: A review of the literature was performed using the MEDLINE, Scopus and Web of Sciences databases from January 1997 to May 2017. The PRISMA guidelines were followed for the conduct of the study. RESULTS: Local recurrence rate ranges between 30 and 54%. Distant recurrence is not often standardized and is reported in up to 50% of cases. The overall 5-year recurrence-free survival rates from 58 to 81%. The mean follow-up of studies included in the analysis ranged from 18 to 350 months. Details on the most important demographic and epidemiological, clinical, histologic and pathologic predictors of recurrence after radical cystectomy are provided through an evidence-based approach. The impact of the extension of lymph node dissection on recurrence after RC is investigated. CONCLUSIONS: A correct prognostic assessment is essential for patients undergoing radical cystectomy for bladder cancer, thereby potentially improving their oncologic outcomes.

Accuracy of elastic fusion biopsy in daily practice: Results of a multicenter study of 2115 patients.

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate.

Clinical impact of 68 Ga-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.

OBJECTIVE: To assess the impact of a novel molecular imaging technique, 68 Ga-(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. PATIENTS AND METHODS: In all, 131 consecutive patients were referred to our centre for a 68 Ga-PSMA PET/CT in the setting of recurring prostate cancer. Of these patients, 11/131(8%) presented with persistent PSA after radical prostatectomy, while 120/131 (92%) were referred for biochemical recurrence after surgery, radiotherapy or both. The images where taken 1 h after injection of 2 MBq/kg of the 68 Ga-(HBED-CC)-PSMA ligand. All examinations were interpreted by two experienced nuclear medicine specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before PSMA imaging. RESULTS: All patients completed the examination with no adverse reactions. The median (interquartile range) PSA level at the time of the examination was 2.2 (0.72-6.7) ng/mL. Overall, 68 Ga-PSMA PET/CT detected at least one lesion suspicious for prostate cancer in 98/131 (75%) patients. There was an impact on subsequent management in 99/131 patients (76%). The main modifications included continuing surveillance (withholding hormonal therapy), hormonal manipulations, stereotaxic radiotherapy, salvage radiotherapy, salvage node dissection or salvage local treatment (prostatectomy, high-intensity focussed ultrasound). CONCLUSION: Our preliminary experience suggests that performing 68 Ga-PSMA PET/CT in patients with prostate cancer with rising PSA after treatment with curative intent can be clinically useful as it changes the treatment strategy in a significant proportion of patients. However, larger prospective trials are needed to validate our present findings.

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.

The morbidity of laparoscopic radical cystectomy: analysis of postoperative complications in a multicenter cohort by the European Association of Urology (EAU)-Section of Uro-Technology.

PURPOSE: To analyze postoperative complications after laparoscopic radical cystectomy (LRC) and evaluate its risk factors in a large prospective cohort built by the ESUT across European centers involved in minimally invasive urology in the last decade. METHODS: Patients were prospectively enrolled, and data were retrospectively analyzed. Only oncologic cases were included. There were no formal contraindications for LRC: Also patients with locally advanced tumors (pT4a), serious comorbidities, and previous major abdominal surgery were enrolled. All procedures were performed via a standard laparoscopic approach, with no robotic assistance. Early and late postoperative complications were graded according to the modified Clavien-Dindo classification. Multivariate logistic regression was performed to explore possible risk factors for developing complications. RESULTS: A total of 548 patients were available for final analysis, of which 258 (47%) experienced early complications during the first 90 days after LRC. Infectious, gastrointestinal, and genitourinary were, respectively, the most frequent systems involved. Postoperative ileus occurred in 51/548 (9.3%) patients. A total of 65/548 (12%) patients underwent surgical re-operation, and 10/548 (2%) patients died in the early postoperative period. Increased BMI (p = 0.024), blood loss (p = 0.021), and neoadjuvant treatment (p = 0.016) were significantly associated with a greater overall risk of experiencing complications on multivariate logistic regression. Long-term complications were documented in 64/548 (12%), and involved mainly stenosis of the uretero-ileal anastomosis or incisional hernias. CONCLUSIONS: In this multicenter, prospective, large database, LRC appears to be a safe but morbid procedure. Standardized complication reporting should be encouraged to evaluate objectively a surgical procedure and permit comparison across studies.

Adapting the robotic platform to small operating theaters: our experience with the side-docking technique for robotic-assisted laparoscopic prostatectomy.

INTRODUCTION: Conventionally, in robotic-assisted laparoscopic prostatectomy (RALP), the robot is entered between the abducted legs of the patient. This approach may present drawbacks, including the limited access to the perineum, the inevitable abduction of the patient's legs, and the limited space available in small operating theaters. To overcome these problems, in our center, we use, from over 5 years, a side-docking technique. We herein describe our technique and a series of patients who underwent RALP using such side-docking procedure. METHODS: In our department, we have applied the side-docking technique for over 5 years, mainly in RALP procedures. The series reported includes 268 men undergoing RALP ± extended lymph node dissection (ePLND) between mid-2010 and 2014. After trocart positioning, the robot is entered at a 45° angle compared to the patient's main axis, coming in from the right side. Patient's legs are minimally abducted to <10°. RESULTS: Mean docking time, from skin incision to full docking was 13 min. 41 % (109/268) of patients underwent simultaneous ePLND, dissecting nodes up till at least the iliac bifurcation. No conversion to open surgery was required. External collisions are infrequent with this configuration: No re-docking was necessary in this cohort. CONCLUSIONS: Side-docking of the da Vinci robot is a safe alternative for RALP. In our department, this technique has faced the proof of time and is routinely used.

Long-term analysis of oncological outcomes after laparoscopic radical cystectomy in Europe: results from a multicentre study by the European Association of Urology (EAU) section of Uro-technology.

OBJECTIVE: To report long-term outcomes of laparoscopic radical cystectomy (LRC) in a multicentre European cohort, and explore feasibility and safety of LRC. PATIENTS AND METHODS: This study was coordinated by European Association of Urology (EAU)-section of Uro-technology (ESUT) with nine centres enrolling 503 patients undergoing LRC for bladder cancer prospectively between 2000 and 2013. Data were retrospectively analysed. Descriptive statistics were used to explore peri- and postoperative characteristics of th ecohort. Kaplan-Meier curves were constructed to evaluate recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Outcomes were also stratified according to tumour stage, lymph node (LN) involvement and surgical margin status. RESULTS: Minor complications (Clavien I-II) occurred in 39% and major (IIIa-IVb) in 17%. In all, 10 (2%) postoperative deaths were recorded. The median (interquartile, IQR) LN retrieval was 14 (9-17) and positive surgical margins were detected in 29 (5.8%) patients. The median (mean, IQR) follow-up was 50 (60, 19-90), during which 134 (27%) recurrences were detected. Actuarial RFS, CSS and OS rates were 66%, 75% and 62% at 5 years and 62%, 55%, 38% at 10 years. Significant differences in RFS, CSS and OS were found according to tumour stage, LN involvement and margin status (log-rank P < 0.001). On multivariate Cox analysis, T stage and LN involvement (both P < 0.001) were significant predictors of RFS, CSS and OS. Positive margins were significant predictors of RFS (P = 0.016) and CSS (P = 0.043). CONCLUSIONS: In this European LRC multicentre study, the largest to date, long-term RFS, CSS and OS rates after LRC appear comparable to those reported in current open RC series. Further randomised controlled trials are necessary to assess the global impact of LRC.

Lower urinary tract dysfunction after nerve-sparing radical hysterectomy.

INTRODUCTION AND HYPOTHESIS: The 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. METHODS: A 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. RESULTS: Our 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. CONCLUSIONS: Available 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.

Penile rehabilitation after pelvic cancer surgery.

Erectile dysfunction is the most common complication after pelvic radical surgery. Rehabilitation programs are increasingly being used in clinical practice but there is no high level of evidence supporting its efficacy. The principle of early penile rehabilitation stems from animal studies showing early histological and molecular changes associated with penile corporal hypoxia after cavernous nerve injury. The concept of early penile rehabilitation was developed in late nineties with a subsequent number of clinical studies supporting early pharmacologic penile rehabilitation. These studies included all available phosphodiesterase type 5 inhibitors, intracavernosal injection and intraurethral use of prostaglandin E1 and to lesser extent vacuum erectile devices. However, these studies are of small number, difficult to interpret, and often with no control group. Furthermore, no studies have proven an in vivo derangement of endothelial or smooth muscle cell metabolism secondary to a prolonged flaccid state. The purpose of the present report is a synthetic overview of the literature in order to analyze the concept and the rationale of rehabilitation program of erectile dysfunction following radical pelvic surgery and the evidence of such programs in clinical practice. Emphasis will be placed on penile rehabilitation programs after radical cystoprostatectomy, radical prostatectomy, and rectal cancer treatment. Future perspectives are also analyzed.

Live surgical education: a perspective from the surgeons who perform it.

OBJECTIVE: To evaluate the experience and views regarding live surgical broadcasts (LSB) among European urologists attending the European Association of Urology Robotic Urology Society (ERUS) congress in September 2012. MATERIALS AND METHODS: An anonymous survey was distributed via email inviting the participants of the ERUS congress with experience of LSB to share their opinions about LSB. The outcomes measured included; personal experience of LSB, levels of anxiety faced and the perceived surgical quality. The impact of factors, such as communication/team-working, travel fatigue and lack of specific equipment were also evaluated. RESULTS: In all, 106 surgeons responded with 98 (92.5%) reporting personal experience of LSB; 6.5% respondents noted 'significant anxiety' increasing to 19.4% when performing surgery away from home (P < 0.001). Surgical quality was perceived as 'slightly worse' and 'significantly worse' by 16.1% and 2.2%, which deteriorated further to 23.9% and 3.3% respectively in a 'foreign' environment (P = 0.005). In all, 10.9% of surgeons 'always' brought their own surgical team compared with 37% relying on their host institution; 2.4% raised significant concerns with their team and 18.8% encountered significantly more technical difficulties. Lack of specific equipment (10.3%), language difficulties (6.2%) and jet lag (7.3%) were other significant factors reported. In all, 75% of surgeons perceived the audience wanted a slick demonstration; however, 52.2% and 42.4% respectively also reported the audience wished the surgeon to struggle or manage a complication during a LSB. CONCLUSIONS: A small proportion of surgeons had significantly heightened anxiety levels and lower perceived performance during LSB, which in a 'foreign' environment seemed to affect a greater proportion of surgeons. Various factors appear to impact surgical performance raising concerns about the appropriateness of unregulated LSB as a teaching method. To mitigate these concerns, surgeons' performing live surgery feel that the operation needs to be well planned using appropriate equipment; with many considering bringing their own team or operating from home on a video link.

Long-term evaluation of oncologic and functional outcomes after laparoscopic open-assisted radical cystectomy: a matched-pair analysis.

PURPOSE: To evaluate peri- and postoperative morbidity, and long-term oncologic and functional results of our laparoscopic radical cystectomy (LRC) technique, comparing it with our standard open approach. METHODS: Between 2000 and 2010, 54 patients underwent LRC for urothelial cell carcinoma of the bladder in two academic hospitals. The procedures were performed by two surgeons. Patients were matched 1:1 with patients who underwent open RC in the same years by the same surgical team. Differences in peri- and postoperative complications across the two groups were assessed using Wilcoxon's rank-sum or χ (2) test. Kaplan-Meier curves, log-rank tests and Cox regression models were constructed to assess differences in recurrence-free survival on long-term follow-up between the two groups. RESULTS: Laparoscopic radical cystectomy was significantly associated with lower blood loss (p < 0.0001) and less frequent postoperative ileus (p = 0.03). Regarding more serious postoperative complications, no difference was found across the two cohorts. Median oncologic follow-up was 42 months (IQR 12-72 months) in the LRC cohort and 18 months (IQR 8-27 months) in patients undergoing open radical cystectomy (ORC). No statistically significant difference in recurrence-free survival was observed between the two groups (log rank p = 0.677). On univariate Cox regression, the surgical approach used was not significantly associated with risk of recurrence. CONCLUSIONS: We found that LRC is safe and associated with lower blood loss and decreased postoperative ileus compared with ORC. Moreover, on long-term oncologic follow-up, LRC appeared non-inferior to ORC with no significant difference in recurrence-free survival. Nonetheless, these results must be confirmed by larger series and stronger long-term follow-up data are needed.

Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911).

BACKGROUND: We report the long-term results of a trial of immediate postoperative irradiation versus a wait-and-see policy in patients with prostate cancer extending beyond the prostate, to confirm whether previously reported progression-free survival was sustained. METHODS: This randomised, phase 3, controlled trial recruited patients aged 75 years or younger with untreated cT0-3 prostate cancer (WHO performance status 0 or 1) from 37 institutions across Europe. Eligible patients were randomly assigned centrally (1:1) to postoperative irradiation (60 Gy of conventional irradiation to the surgical bed for 6 weeks) or to a wait-and-see policy until biochemical progression (increase in prostate-specific antigen >0·2 µg/L confirmed twice at least 2 weeks apart). We analysed the primary endpoint, biochemical progression-free survival, by intention to treat (two-sided test for difference at α=0.05, adjusted for one interim analysis) and did exploratory analyses of heterogeneity of effect. This trial is registered with ClinicalTrials.gov, number NCT00002511. FINDINGS: 1005 patients were randomly assigned to a wait-and-see policy (n=503) or postoperative irradiation (n=502) and were followed up for a median of 10·6 years (range 2 months to 16·6 years). Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait-and-see policy (198 [39·4%] of 502 patients in postoperative irradiation group vs 311 [61·8%] of 503 patients in wait-and-see group had biochemical or clinical progression or died; HR 0·49 [95% CI 0·41-0·59]; p<0·0001). Late adverse effects (any type of any grade) were more frequent in the postoperative irradiation group than in the wait-and-see group (10 year cumulative incidence 70·8% [66·6-75·0] vs 59·7% [55·3-64·1]; p=0.001). INTERPRETATION: Results at median follow-up of 10·6 years show that conventional postoperative irradiation significantly improves biochemical progression-free survival and local control compared with a wait-and-see policy, supporting results at 5 year follow-up; however, improvements in clinical progression-free survival were not maintained. Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins, but could have a detrimental effect in patients aged 70 years or older. FUNDING: Ligue Nationale contre le Cancer (Comité de l'Isère, Grenoble, France) and the European Organisation for Research and Treatment of Cancer (EORTC) Charitable Trust.

Localising prostate cancer: comparison of endorectal magnetic resonance (MR) imaging and 3D-MR spectroscopic imaging with transrectal ultrasound-guided biopsy.

BACKGROUND: Magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) have been gaining acceptance as tools in the evaluation of prostate cancer. We compared the accuracy of transrectal ultrasound (TRUS)-guided biopsy and dynamic contrast-enhanced MRI combined with three-dimensional (3D) MRSI in locating prostate tumours and determined the influence of prostate weight on MRI accuracy. PATIENTS AND METHODS: Between March 1999 and October 2006, 507 patients with localised prostate cancer underwent radical prostatectomy (RP) at the Jules Bordet Institute. Of these, 220 had undergone endorectal MRI (1.5 T Siemens Quantum Symphony) and 3D-MRSI prior to RP. We retrospectively reviewed data on tumour location and compared the results obtained by MRI and by TRUS-guided biopsy with those obtained on histopathology of the RP specimen. RESULTS: Patient data were as follows: median age 62.4 years (45-74); median PSA 6.36 ng/ml (0.5-22.6); 73.6% of patients had non-palpable disease (T1c); median biopsy Gleason score 6 (3-9); median RP specimen weight 50 g (12-172); median pathological Gleason score 7 (4-10); 68.64% of patients had organ-confined (pT2) disease. Tumour localisation was correlated with RP data in a significantly higher percentage of patients when using MRI rather than TRUS-guided biopsy (47.4 vs. 36.6%, p < 0.0001). MRI was marginally superior to TRUS-guided biopsy in detecting malignancy at the prostate apex (48.3 vs. 41.9%, p = 0.0687) and somewhat better at the prostate base (46 vs. 39.1%, p = 0.0413). It was highly significantly better at mid-gland (52 vs. 41.1%, p = 0.0015) and in the transition zone (40.1 vs. 24.3%, p < 0.0001). MRI had higher sensitivity in larger (≥50 g) than smaller (<50 g) prostates (50.3 vs. 42.2%, p = 0.0017). CONCLUSIONS: MRI was superior to TRUS-guided biopsy in locating prostate tumours except at the gland apex. MRI was more accurate in larger (≥50 g) than smaller prostates.

Oncological outcomes of salvage radical prostatectomy for recurrent prostate cancer in the contemporary era: A multicenter retrospective study.

BACKGROUND: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.

The learning curve for laparoscopic radical prostatectomy: an international multicenter study.

PURPOSE: It is not yet possible to estimate the number of cases required for a beginner to become expert in laparoscopic radical prostatectomy. We estimated the learning curve of laparoscopic radical prostatectomy for positive surgical margins compared to a published learning curve for open radical prostatectomy. MATERIALS AND METHODS: We reviewed records from 8,544 consecutive patients with prostate cancer treated laparoscopically by 51 surgeons at 14 academic institutions in Europe and the United States. The probability of a positive surgical margin was calculated as a function of surgeon experience with adjustment for pathological stage, Gleason score and prostate specific antigen. A second model incorporated prior experience with open radical prostatectomy and surgeon generation. RESULTS: Positive surgical margins occurred in 1,862 patients (22%). There was an apparent improvement in surgical margin rates up to a plateau at 200 to 250 surgeries. Changes in margin rates once this plateau was reached were relatively minimal relative to the CIs. The absolute risk difference for 10 vs 250 prior surgeries was 4.8% (95% CI 1.5, 8.5). Neither surgeon generation nor prior open radical prostatectomy experience was statistically significant when added to the model. The rate of decrease in positive surgical margins was more rapid in the open vs laparoscopic learning curve. CONCLUSIONS: The learning curve for surgical margins after laparoscopic radical prostatectomy plateaus at approximately 200 to 250 cases. Prior open experience and surgeon generation do not improve the margin rate, suggesting that the rate is primarily a function of specifically laparoscopic training and experience.