[Oncological and functional results of focal treatment of localized prostate cancer with HIFU]. / Résultats oncologiques et fonctionnels du traitement focal du cancer de prostate localisé par HIFU.

INTRODUCTION: In recent years, improved diagnosis of prostate cancer has allowed the development of focal therapy, in order to reduce the morbidity of treatments. Our study assesses the medium-term oncological and functional results of FocalOne® HIFU treatment in localized prostate cancer. METHODS: This is a retrospective, multicentre study including patients with low- or intermediate-risk localized prostate cancer treated with Focal one HIFU between November 2014 and December 2019. The primary endpoint was the retreatment rate and subgroup analyses were performed to identify predictive factors of retreatment. RESULTS: One hundred and thirty-seven patients were included with a median follow-up of 25.5 months. Seventy percent of patients had clinical stage T2, 64% had an ISUP score of 2 or 3 on initial biopsies and 38% were treated with hemi-ablation. Follow-up biopsies were performed in 76.6% of patients during follow-up with 21.8% having clinically significant cancers. The retreatment rate at 24 months was 37.2%, with positive biopsies being the primary criterion for retreatment. Patients with a PSA>8ng/mL had a significantly higher retreatment rate. Finally, morbidity remained acceptable with 5.8% of patients requiring reoperation for complications and 21% for de novo erectile dysfunction. CONCLUSION: Our results are in agreement with those of the literature, seeming to indicate a lower morbidity of the focal treatment by HIFU compared to the radical treatments while offering an acceptable oncological control. Prospective randomized trials are ongoing.

[Digital transformation of perioperative nurse-coordinated protocols in renal surgery for enhanced recovery and outpatient surgery using UroConnect® application]. / Digitalisation de la coordination infirmière des parcours périopératoires de chirurgie rénale en réhabilitation améliorée et ambulatoire par l'application UroConnect®.

Robot Assisted Partial Nephrectomy (RAPN) is a standard of care for localized renal tumors. It allows a good carcinological control while limiting complications. Despite numerous benefits, the economic sustainability of robotic assistance remains a challenge in the French health care system. The introduction in our institution of two perioperative nurse-coordinated protocols for patients undergoing RAPN (Enhanced Recovery After Surgery: NP-RAAC in 2015 and Outpatient: Ambu-Rein in 2016) is associated with a shortening of the average length of hospital stay, thus reducing the cost of robotic assisted procedures. With the aim of improving efficiency of nursing support within these protocols, we have introduced digitalized nursing coordination by developing a urological perioperative application: UroConnect®. This device is offered to patients by the coordinating nurses during a preoperative visit. It provides information on the pathology and its surgical management. Self-completed questionnaires sent at key moments collect data from the first month after surgery and detect patients presenting difficulties or complications, allowing the nurses to respond with appropriate care. The application allows a secure discharge, a personalised follow-up and an increase in the patient's autonomy and compliance with care.

[Prostatic Urethral Lift under local anesthesia: Single-centre retrospective observational study]. / La pose d'implant UroLift ® sous anesthésie locale : étude observationnelle rétrospective monocentrique.

INTRODUCTION: Urolift implant placement may be preferred to conventional endoscopic surgery for patients who wish to preserve their sexuality or for those who prefer a rapid post-operative recovery. The absence of general anaesthesia is an important element that reinforces the minimally invasive aspect of the procedure and improves the speed of recovery. The aim of this work was to report our preliminary experience of Urolift treatment under local anaesthesia. MATERIALS AND METHODS: A retrospective analysis was conducted including all patients treated with Urolift between 2017 and 2021 in our centre. Local anaesthesia was based on the instillation of 2 Xylocaine gels at 4°C into the urethra 15minutes before the procedure. The primary endpoint was the successful completion of the procedure without interruption due to pain or the need for any other form of anaesthesia or analgesia. RESULTS: Twenty-seven patients were included with a median age of 65 years and a prostate volume of 46mL. The International Prostate Symptom Score (IPSS) was 23. The first 3 patients were operated on under general anaesthesia. Local anaesthesia was introduced from the fourth patient onwards. There was no recourse to other modalities of analgesia or anaesthesia or interruption of the procedure. The operating time was 10minutes and pain was assessed at 1 on a visual analogue scale. At 3 months, the IPSS score was 9 (P=0.001). CONCLUSION: This preliminary experience confirms the feasibility of placing the Urolift implant under local anaesthesia without any failure of the proposed management. The improvement in IPSS score was consistent with previously published clinical trials. LEVEL OF EVIDENCE: 3.

[Urinary drainage of spinal cord injured patients in the acute phase of trauma: A descriptive, retrospective study]. / Drainage urinaire des blessés médullaires à la phase aiguë du traumatisme : étude descriptive, rétrospective.

INTRODUCTION: Urinary retention in the acute phase of a spinal cord injury (SCI) requires bladder drainage (BD). International scientific societies recommend early implementation of intermittent catheterisation (IC) to prevent lower urological complications, preserve fertility, the urological future of the patient and improve its quality of life. The aim of our study was to analyze the mode of BD in the acute phase of a trauma in patients with SCI. MATERIALS AND METHODS: We retrospectively analyzed the mode of BD of patients with SCI in the acute phase of trauma at the Bordeaux University Hospital from 2013 to 2018. RESULTS: The care pathways of 81 patients were analyzed; patients were hospitalized in intensive care unit (ICU) (42%, n=34), in orthopaedic ward (19.8%, n=16) or in ICU and orthopaedic ward (38.2%, n=31). All of them had an indwelling catheter (IUD) inserted before IC was introduced in 56 of them (69%). On hospital discharge, IC was the BD for only 37% of patients, with differences according to the care pathway: 65% of patients leaving ICU were on IC, compared with 11% leaving orthopaedic ward. 80% of patients who had IC in ICU had an IUD installed in orthopaedic ward. CONCLUSION: In this study, during the acute phase of a trauma in the majority of SCI patient, IC was introduced only in a minority of patients and the promotion was different within the hospital care pathways. Those results enhanced the need for IC awareness in different hospital units to standardize the best patient care. LEVEL OF EVIDENCE: 3.

[Predictive factors of active surveillance interruption for prostate cancer after 5years of follow-up]. / Surveillance active du cancer de prostate : facteurs prédictifs d'échecs après 5 ans de suivi.

INTRODUCTION AND PURPOSE: The objective of this work was to identify the risk factors (RFs) of active surveillance (AS) interruption in a prostate cancer (PCa) single-center retrospective cohort of patients. MATERIAL AND METHOD: All patients in AS between January 2011 and October 2019 were retrospectively included in a computerized database. The group of patients who had an AS interruption was compared to the one still under AS, in order to identify potential risk factors for the interruption of the surveillance protocol. RESULTS: Two hundred and two patients have been included in the AS cohort with a median follow-up of 32months. At the time of analysis, 72 patients (36%) were not under the AS protocol anymore, 118 (58%) were still under AS and 12 (6%) were lost of follow-up. Sixty-six patients (92%) had left SA due to PCa progression, 4 (5%) by personal choice and 2 (3%) switched to watchful waiting. A PSA doubling Time<3years (PSADT<3years) has been identified as the only statistically significant RF for AS interruption, both in the unvaried (P<0.001) and multivariate (OR=5.403, P<0.01) analysis. It was also the only RF of AS interruption in the early analysis in the first three years of AS, in the unvaried analysis (P=0.021) and the multivariate analysis (OR=3.612, P=0.018). CONCLUSION: PSADT was the only RF of AS early and late interruption in our study. It represents a major inclusion criterion in AS protocol during the initial assessment. LEVEL OF EVIDENCE: 3.

Active surveillance in prostate cancer is possible for Afro-Caribbean population: Comparison of oncological outcomes with a Caucasian cohort.

BACKGROUND: Prostate cancer is supposedly more aggressive among Afro-Caribbean men. There is a lack of data in this population for active surveillance. Published series are retrospective or have small samples and results are discordant. The objective was to determinate whether actual active surveillance modalities can be applied for Afro-Caribbean men by comparing their oncological outcomes with Caucasian men. METHODS: A total of 449 consecutive patients who underwent active surveillance for favorable-risk prostate cancer in two French University-Medical-Centers between 2005 and 2018: 261 in Guadeloupe, French West Indies, and 188 in Bordeaux, metropolitan France. Median follow-up was 56 months, (95% CI [32-81]) and 52 months (95% CI [30-75]), respectively (P=0.07). Curative treatment was given in case of histological, biological, or imaging progression, or upon patient demand. Primary endpoints were treatment-free, overall and specific survival. Secondary outcomes were reasons of discontinuating active surveillance, histological poor prognosis factors after prostatectomy, CAPRA-S score, biochemical-recurrence-free after treatment and metastasis-free survival. Kaplan-Meier method was used. RESULTS: Median treatment free survival was 58.4 months (CI 95% [48.6-83.1]) for ACM and not reached at 120 months for CM (P=0.002). Overall survival (P=0.53), and specific survival (P=0.21) were similar in the two groups. CM were likely to have poor prognosis factor on prostatecomy piece (57 vs 30%, P=0.01). No difference for repartition of the CAPRA-S score (P=0.86), biochemical-recurrence-free (P=0.92) and metastasis-free (P=0.44) survival. CONCLUSIONS: Oncological outcomes for active surveillance of Afro-Caribbean and Caucasian men were similar in terms of mortality, recurrence and metastasis in our bicentric study, showing usability of current criteria for Afro-Caribbean. The higher rate of disease progression in the Afro-Caribbean population requires close monitoring. LEVEL OF EVIDENCE: 3.

[Prostate cancer microenvironment: Its structure, functions and therapeutic applications]. / Microenvironnement du cancer de la prostate : structure, fonctions et applications thérapeutiques.

INTRODUCTION: In the field of prostate cancer there is a growing tendency for more and more studies to emphasise the predominant role of the zone situated between the tumour and the host: the tumour microenvironment. The aim of this article is to describe the structure and the functions of the prostate cancer microenvironment as well as the principal treatments that are being applied to it. MATERIAL AND METHODS: PubMed and ScienceDirect databases have been interrogated using the association of keywords "tumour microenvironment" and "neoplasm therapy" along with "microenvironnement tumoral" and "traitements". Of the 593 articles initially found, 50 were finally included. RESULTS: The tumour microenvironment principally includes host elements that are diverted from their primary functions and encourage the development of the tumour. In it we find immunity cells, support tissue as well as vascular and lymphatic neovascularization. Highlighting the major role played by this microenvironment has led to the development of specific treatments, notably antiangiogenic therapy and immunotherapy. CONCLUSION: The tumour microenvironment, the tumour and the host influence themselves mutually and create a variable situation over time. Improvement of the knowledge of the prostate cancer microenvironment gradually enables us to pass from an approach centred on the tumour to a broader approach to the whole tumoral ecosystem. This enabled the emergence of new treatments whose place in the therapeutic arsenal still need to be found.

[Head to head comparison of two currently used nomograms predicting the risk of side specific extra capsular extension to indicate nerve sparing during radical prostatectomy for treatment of prostate cancer]. / Validation externe des nomogrammes de prédiction de l'extension extra-prostatique spécifiquement au côté pour des patients atteints de cancer de prostate traités par prostatectomie totale.

OBJECTIVE: To perform a head to head comparison of these two nomograms by an external validation combined with an identification of probability cut-offs when to indicate NS. METHODS: The full models of the nomograms of Ohori et al. and Steuber et al. were used to calculate the risk of ECE based on PSA and side specific information on clinical stage, biopsy Gleason score, % positive cores, and % cancer in cores. A dataset of 968 prostate half lobes was used retrospectively for analysis. All patients underwent laparoscopic robot-assisted or open radical prostatectomy for localized prostate cancer. RESULTS: The predictive accuracy of the Ohori nomogram was at 0.80 and for the Steuber Nomogram at 0.78 (comparison P > 0.05). In the calibration plot, the Ohori nomogram showed less departures from ideal predictions than the Steuber nomogram. The best probability cut-off to allow NS for the Ohori nomogram seemed to be ≤ 10%, permitting NS in 59.7% of all cases and being associated with a false negative rate of 10%. The best cut-off for the Steuber nomogram seemed to be ≤ 8%, permitting NS in 44% and associated with a false negative rate 12.5%. CONCLUSIONS: The Ohori et al. and the Steuber et al. nomograms allow highly accurate and comparable predictions of the risk of side specific ECE. LEVEL OF EVIDENCE: 4.

Switching from the transrectal to the transperineal route: A single center experience.

INTRODUCTION: This study aimed to evaluate the feasibility of switching from transrectal to transperineal prostate biopsy (TPPBx) by urologists with no previous experience with TPPBx. Material A monocentric clinical study with exhaustive and consecutive inclusions was conducted between January and November 2021, including 105 consecutive patients who underwent TPPBx performed by two senior urologists with no previous experience of TPPBx (GR, FB). Biopsies were performed under local anesthesia (LA) without antibioprophylaxis. The main objective was to assess the safety of this procedure. Adverse events were classified according to the Clavien-Dindo score. The secondary objectives were to assess the level of pain experienced during the different steps of the procedure using a numerating rating scale (NRS), the rate of clinically significant prostate cancer (csPCa) detected, and the level of anxiety using the Hospital Anxiety and Depression Scale (HAD). RESULTS: No major complications (Clavien-Dindo score≥3) were reported. One patient presented with acute urinary retention (1%) and a urinary tract infection (1%). Other adverse events were hematuria (43%), hemospermia (23%), rectal bleeding (1%), perineal hematoma (3%), persistent perineal pain (5%), and de novo erectile dysfunction (2%). The median level of pain on NRS for the procedure was 2.00 (IQ: 1.00-4.00); it was 3.00 (IQ: 2.00-5.00) during LA and 3.00 (IQ: 2.00-5.00) during punctions. In anxious patients (HAD score>10), the level of pain during the procedure was 2.5 (IQ: 2.00-3.00). Overall, csPCa was detected in 63%. CONCLUSION: TPPBx under LA without antibioprophylaxis provides few complications, an acceptable pain threshold, and a satisfactorily rate of csPCa detection, even if performed by urologists with no previous experience of TPPBx.

Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

BACKGROUND: Sunitinib is a standard of care for metastatic renal cell carcinoma (mRCC). Hypothyroidism is frequently observed under sunitinib therapy. This study was conducted to prospectively determine the correlation between thyroid function and progression-free survival (PFS) in this population. PATIENTS AND METHODS: One hundred and eleven mRCC patients treated with sunitinib were evaluated for serum thyroid-stimulating hormone (TSH) and T4 levels before treatment and every 6 weeks during treatment. Survival was analysed according to a landmark method with a cut-off of 6 months, excluding early progressive or early-censored patients. RESULTS: Out of the 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction, including 95% hypothyroidisms out of which 90.9% received L-thyroxine replacement. Median time to TSH alteration was 5.4 months. Median PFS was 11.7 months for the entire population. Median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months, respectively, log-rank P = 0.94, hazard ratio = 1.02, 95% confidence interval = 0.54-1.93). There was no difference even after adjustment for Memorial Sloan-Kettering Cancer Centre classification and therapy line. CONCLUSIONS: Abnormal thyroid function with hormonal substitution did not increase survival in our population, independent of initial prognosis and previous treatments. Larger comparative studies are deserved to validate these conclusions.

[Strategies in castration-resistant prostate cancer]. / Stratégies thérapeutiques du cancer de la prostate résistant à la castration.

The treatment of a castration-resistant prostate cancer can be immediate or delayed according to the circumstances and the time of its occurrence. New therapeutic targets have been determined with basic tumor biology studies. Treatments available or on development are various and range from estrogens to new anti-androgens. Endothelin inhibitors, abiraterone, MDV3100 or RD162 are the most promising examples but they require to enroll patients in therapeutic trials.

[Real time elastography in the diagnosis of prostate cancer: comparison of preoperative imaging and histology after radical prostatectomy]. / Élastographie en temps réel pour l'identification du cancer de prostate : comparaison d'imagerie préopératoire avec l'anatomopathologie après prostatectomie totale.

INTRODUCTION: Conventional grey scale ultrasound has only limited sensitivity and specificity in the detection of prostate cancer. Real time elastography is a promising modality to overcome this problem. The goal of the current study was an evaluation of real time elastography for the correct detection of prostate cancer lesions in prostatectomy specimens. PATIENTS AND METHODS: Between 11/2008 and 05/2009, 28 patients diagnosed with prostate cancer and scheduled for radical prostatectomy underwent real time elastography before radical prostatectomy. Elastography was performed using a Hitachi(®) EUB 7500 ultrasound machine with a V53W rectal probe at 7,5MHz by one operator. During the exam, each prostate was partitioned into 12 sectors (anterior, posterior, left, right, base, middle gland, apex). Suspect zones were identified and filed depending on their localization. The prostatectomy specimens were processed according to the Stanford protocol in 3-5mm step sections. The preoperative and postoperative results regarding tumor localization were compared. RESULTS: In total, 88 cancer lesions could be identified in the prostatectomy specimen, where 125 sectors were positive for a total of 336 sectors evaluated. Based on elastography 134 suspicious sectors were identified. For real time elastography, the sensitivity and specificity for correct cancer identification were 73.4 and 79.0 %, respectively. The negative and positive predictive value was 83.4 and 67.4 %, respectively. Accuracy for correct identification of the tumor lesion was 76.5 %. CONCLUSION: In this study, real time elastography showed high accuracy in the identification of prostate cancer lesions in the prostate. Routine use of elastography could improve the diagnosis of prostate cancer, as well as the therapeutic management.

[Initial results of a novel technique for sperm retrieval in male infertility due to refractory retrograde ejaculation]. / Résultats préliminaires d'une nouvelle technique de recueil du sperme vésical en présence d'éjaculation rétrograde réfractaire au traitement médical.

AIMS: To describe and evaluate a novel technique of spermatozoa retrieval from patients suffering from infertility secondary to refractory retrograde ejaculation. METHOD: Prospective study to compare mobility and vitality of spermatozoa obtained from urine (U) after oral modification of chemical parameter (PH, Osmolarity) versus from endovesical instillation of sterile spermatozoa culture medium before ejaculation (F). Patients were their own controls. Twelve month prospective follow-up was achieved to document the results of assisted procreation. RESULTS: Eight patients were included and mobility and vitality were improved in all patients after F technique was compared to U technique. With U technique, eight patients on eight had negative defrost test; after F technique, seven patients on eight had a positive defrost test and could therefore have access to assisted reproduction techniques. Four couples had five ICSI and obtained three pregnancies leading to five births. CONCLUSION: Endovesical instillation of sterile spermatozoa culture medium before ejaculation was a safe and effective technique to improve spermatozoa quality in male infertility related to refractory retrograde ejaculation.

Resection of residual masses after chemotherapy for advanced non-seminomatous germ cell tumours, a monocentric analysis of pre-operative prognosticators.

Removal of residual masses after chemotherapy in non-seminomatous germ cell tumours (NSGCTs) remains the standard of care. We evaluated in a retrospective and monocentric study potential prognostic factors. Fifty-one patients underwent surgery after chemotherapy for NSGCT. We estimated event-free survival with Kaplan-Meier method and used Cox proportional hazards regression analysis to assess the prognostic significance of risk factors. Histology of residual masses revealed fibrosis in 25 (49%), mature teratoma in 18 (35%) and viable germ cells in 8 (16%). Alpha-fetoprotein mean level at diagnosis was higher in patients with residual masses showing mature teratoma and/or viable malignant cells (P = 0.036). In multivariate analysis, poor prognosis group according to International Germ Cell Cancer Collaborative Group was associated with worse outcome compared with good and intermediate prognosis groups (hazard ratio for events = 26.4; 95% confidence interval 2.46-283.9; P = 0.006) and primary testicular NSGCT was associated with better event-free survival than extragonadal NSGCTs (hazard ratio for events = 0.04; 95% confidence interval 0.004-0.48; P = 0.01). Resection of residual masses after chemotherapy in NSGCT results in favourable long-term survival in most patients. Our results compared favourably with those reported from higher volume centres.

[Urinary incontinence following open prostatectomy or laparoscopy for local prostate cancer. A review of relevant literature]. / Incontinence urinaire après prostatectomie ouverte ou laparoscopique pour cancer prostatique localisé. Une revue de la littérature.

AIM: Evaluate urinary continence after radical prostatectomy. MATERIALS AND METHOD: Recent series about urinary continence were studied. RESULTS: In seven articles analyzed, continence fluctuated between 63.6 and 91.9%. Evaluation benchmarks were depending on study. Unlike self-questionnaires, objective criteria (pad test) should be more reliable. Carcinologic prognostic factors were not implicated directly. The most frequently preoperative risk factors of incontinence were: age, BMI. Peroperative parameters, attesting of surgical difficulties could have a functional impact. Bladder neck preservation could affect the recovery velocity but not functional results. Length of catheterization and lack of urinary rehabilitation could be influent. The mean of continence evaluation after radical prostatectomy was different for each study. CONCLUSION: Comparability was difficult because operative technique, group's features and mean of functional evaluation were different from study to study. Several risk factors were found but without consensus. It would be necessary to separate carcinologic and functional risk factors.

[Robot-assisted radical prostatectomy: Perioperative complications, pathological results and functional results during the learning curve]. / La prostatectomie totale robot-assistée : complications périopératoires, résultats anatomopathologiques et fonctionnels pendant la période d'initiation.

OBJECTIVE: We report our experiences regarding the peri- and postoperative complications as well as pathological and functional results of robot-assisted radical prostatectomy during the implementation phase and the learning curve of the technique. MATERIAL: All clinical, paraclinical, as well as peri- and postoperative events of the first 102 patients were filed. Postoperative complications were classified according to the Clavien classification. Regarding functional results, continence was defined as the use of 0 pads or one pad for security reasons. Erectile function was classified into absence of spontaneous erections, erections insufficient for sexual intercourse and erections sufficient for sexual intercourse. RESULTS: Median procedure time was 240min, blood-loss 400mL and transfusion rate 2%. Overall, 7.8% of all patients had perioperative complications, 13.7% had minor and 4.9% had mayor post operative complications. The overall positive surgical margin rate was 16.0%. At 12month, 87% of all patients were continent and 21.1% had spontaneous erections and 47.4% had sexual intercourse. CONCLUSION: Patients treated during the implementation phase of robot-assisted radical prostatectomy show rates of peri- and postoperative complications, as well as pathological and functional results comparable to the results of centers of excellence published in the literature.

[Robotic-assisted radical prostatectomy]. / Prostatectomie totale robot-assistée.

The beginning of the 21st century has ushered the new era of robotic surgery that now challenges conventional open surgery. Robotic surgery has been embraced by urologists who have applied it to complex surgical procedures such as radical prostatectomy. The revolutionary improvements provided by the Da Vinci Surgical System combines superior 3D visualization along with enhanced dexterity such as the endowrist allowing distal supranatural rotation of instruments, precision and control in an intuitive, ergonomic interface with breakthrough surgical dissection and suturing capabilities in confined spaces. Da Vinci Surgical System allows to perform nerve sparing radical prostatectomy techniques in various surgical plans (inter, intra and extrafascial) with a shorter learning curve and probably outcomes more rapidly reproducible by a less experienced laparoscopic surgeon.

[Two-years follow-up of radiofrequency thermotherapy for urination disorders due to benign prostatic hyperplasia]. / Résultat à deux ans de la thermothérapie prostatique par radiofréquence pour troubles mictionnels liés à l'HBP.

AIM: To describe medium-term functional results of Transurethral Needle Ablation (TUNA) to treat symptomatic benign prostatic hyperplasia (BPH) refractory to medical treatment. MATERIALS AND METHOD: Patients who completed at least 2 years follow-up after TUNA were systematically offered a reevaluation including: Flowmetry, PSA, symptom score (IPSS), satisfaction index visual analogic scale (VAS) and a treatment impact evaluation with a Likert scale (ranging from much worse to much improved). RESULTS: From December 2002 to January 2007, 45 patients were treated with TUNA under local regional anaesthesia (prostatic block). Twenty-seven of them were followed-up longer than 24 months (median follow-up 44 months [26-52]). Changes in the selected outcomes were: increase in Qmax from 9.5 mL/s preoperatively to 9 mL/s at 6 month and 11.5 mL/s after 2 years; increase in IPSS from 19.3 before TUNA to 16.3 at 6 month and 16.5 after 2 years. About subjective evaluation, 58% of patient gave a satisfaction VAS>or=6, and the improvement index was greater or equal to +1 in 67% of case. CONCLUSION: In this initial monocentric experiment, despite a modest improvement of objective parameters and a 20% of retreatment rate, TUNA give contentment and improvement sensation for 60% of patients who were treated for non-efficiency of medical treatment for benign prostatic hyperplasia.

Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer.

BACKGROUND: Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer. PATIENTS AND METHODS: This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other. RESULTS: Median age was 69 years (range 51-77 years), and median PSA 102 ng/ml (range 3-1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the >or=20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients. CONCLUSION: Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.