Frédéric Staerman

Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study

BACKGROUND Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. OBJECTIVE To update our experience in the largest worldwide prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤ 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤ 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. RESULTS AND LIMITATIONS In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. CONCLUSIONS Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. TRIAL REGISTRATION The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).

Short-term outcomes of the prospective multicentre ‘Prostate Cancer Research International: Active Surveillance’ study

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

Radical Prostatectomy for Low-Risk Prostate Cancer Following Initial Active Surveillance: Results From a Prospective Observational Study

BACKGROUND Little is known about the outcome of radical prostatectomy (RP) in men initially followed on active surveillance (AS) for low-risk prostate cancer (PCa). OBJECTIVE Evaluate pathology findings after RP in our prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS All men participated in the Prostate Cancer Research International: Active Surveillance (PRIAS) study. Eligible men were initially diagnosed with low-risk PCa (clinical stage ≤ T2, prostate-specific antigen [PSA] ≤ 10 ng/ml, PSA density <0.2 ng/ml per ml, one or two positive biopsy cores, and Gleason score ≤ 6) and underwent RP between December 2006 and July 2011. The study protocol recommends RP in case of risk reclassification on repeat biopsy (Gleason score >6 and/or more than two positive cores) or a PSA doubling time ≤ 3 yr. MEASUREMENTS Descriptive statistics were used to report on pathology findings for staging and grading. RESULTS AND LIMITATIONS Pathology results were available in 167 out of 189 RP cases (88.4%). Median time to RP was 1.3 yr (range: 1.1-1.9). Protocol-based recommendations led to deferred RP in 143 men (75.7%); 24 men (12.7%) switched because of anxiety, and 22 (11.6%) had other reasons. Pathology results showed 134 (80.8%) organ-confined cases and 32 (19.2%) cases with extracapsular extension. Gleason scores ≤ 6, 3+4, 4+3, and 8 were found in 79 (47.3%), 64 (38.3%), 21 (12.6%), and 3 (1.8%) cases, respectively. Unfavourable RP results (pT3-4 and/or Gleason score ≥ 4+3) were found in 49 patients (29%), of whom 33 (67%) had a biopsy-related reason for deferred RP. CONCLUSIONS RP results in men initially followed on AS show organ-confined disease and favourable Gleason grading in a majority of cases. Most men in our cohort had a protocol-based reason to switch to deferred RP. A main focus for AS protocols should be to improve the selection of patients at the time of inclusion to minimise reclassification of risk and preserve the chance for curative treatment, if indicated.

Cancer de la prostate

Mutations “ciblables” dans les cancers de la prostate métastatiques Fruit de la collaboration entre de grandes institutions américaines et européennes, un groupe de chercheurs international (1) a analysé, par séquençage systémique de l’exome entier et du transcriptome, les échantillons de 150 patients atteints d’un cancer de la prostate résistant à la castration métastatique (CPRCm). Près de 90 % des hommes testés présentaient au moins 1 mutation permettant de prédire une réponse ou une résistance à des thérapies connues. Des mutations au niveau du récepteur des androgènes (RA) ont été notées chez près du tiers des patients (63 %). Les autres anomalies génomiques retrouvées le plus fréquemment concernaient les gènes de fusion ETS, TP53 et PTEN (40 à 60 % des cas) avec, par rapport aux cancers de la prostate primaires, un enrichissement des altérations du RA et de TP53. De nouvelles altérations ont été identifiées : PI3K3CA/B, R-spondin , BRAF/RAF1, APC, β-caténine, ZBTB16/PLZF. Mais la découverte sans doute la plus importante est le fait, encore une fois par rapport aux tumeurs primaires, que de nombreux patients (23 %) présentaient des mutations des gènes de la réparation de l’ADN, comme BRCA2, BRCA1 et ATM, ouvrant des perspectives thérapeutiques particulières. Ces patients pourraient répondre à des inhibiteurs de PARP, comme l’olaparib (2) .

Renal Cell Carcinoma (RCC) in Patients With End-Stage Renal Disease Exhibits Many Favourable Clinical, Pathologic, and Outcome Features Compared With RCC in the General Population

BACKGROUND Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

ZSI 375 artificial urinary sphincter for male urinary incontinence: a preliminary study.

Study Type – Therapy (case series)

Erectile Function and Sexual Satisfaction Before and After Penile Prosthesis Implantation in Radical Prostatectomy Patients: A Comparison with Patients with Vasculogenic Erectile Dysfunction

INTRODUCTION Patients with erectile dysfunction (ED) after radical prostatectomy (RP) may benefit from penile prosthesis (PP) implantation after failure of less invasive treatments. Aim.  To assess surgical outcomes and satisfaction after PP implantation in RP patients and compare the results with those in patients with vasculogenic ED (controls). METHODS A database of 415 consecutive PPs (January 1996-December 2008) was used to collate data on preimplantation ED treatments, surgical complications, satisfaction, and International Index of Erectile Function (IIEF) scores before and 3 months after implantation. The results for 90 post-RP implants (79 primary, 11 secondary) and 131 implants for vasculogenic ED were compared. MAIN OUTCOME MEASURES The main outcome measures of this study are intra- and postoperative complications and IIEF domain scores. RESULTS Mean follow-up of RP patients was 37.6 ± 26.8 months. Mean interval between RP and PP implantation was 31.5 ± 28.7 months. Nearly all primary implants (96.2%) were inflatable (3-piece, 70.1%; 2-piece, 24.1%). There was no significant difference between groups in terms of rates of infection (1.1%), mechanical failure (3.3%), and other surgical complications requiring revision surgery (migration, auto-inflation) (4.4%). For primary implants, the mean preimplantation IIEF score (all items) was significantly lower in RP patients than in controls (14.7 ± 5.9 vs. 22.6 ± 10.8, P = 0.003), chiefly because of significantly lower scores for erectile function, intercourse satisfaction, and orgasmic function. After PP implantation in RP patients, the scores for all domains improved, but the total score remained significantly lower than in controls (63.1 ± 7.0 vs. 68.5 ± 6.9, P = 0.005). The orgasmic function score was significantly lower (P < 0.001). Overall satisfaction rate was 86.1% in RP patients and 90.7% in controls (P = 0.3). CONCLUSIONS PP implantation after RP is associated with low morbidity and high satisfaction. It improves the scores for all IIEF domains and, in particular, erectile function. Fibrosis of the retropubic space may require a second incision for reservoir placement or implantation of a 2-piece PP.

Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy

BACKGROUND Calcinosis cutis (CC) encompasses debilitating complications of connective tissue disorders and chronic venous insufficiency. Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment for urolithiasis, pancreatolithiasis, and calcified tendinitis. This study prospectively evaluated ESWL efficacy and tolerance for patients with CC. METHODS This monocentric prospective study included all consecutive patients with CC progressing for at least 3 months, while their underlying causal disease was not. They underwent 3 ESWL sessions at 3-week intervals. The CC area and associated pain (visual analog scale score and analgesic consumption) were recorded before and 6 months after ESWL. RESULTS Eight patients were included: 4 with chronic venous insufficiency, 3 with systemic scleroderma, and one with dermatomyositis. ESWL was used to treat 10 CC lesions. Seven patients completed 3 ESWL sessions. Six months after ESWL, the median CC area had decreased from 3.1 to 1.9 cm(2). visual analog scale-assessed pain scores declined dramatically, from 7 to 2 of 10, as did analgesia consumption, without any difference according to the causal disease. LIMITATIONS Only 8 consecutive patients have been included and treated by ESWL during our study. CONCLUSION This evaluation of ESWL efficacy and tolerance for the treatment of CC found no difference between the different underlying CC causal diseases in terms of efficacy. Based on our observations, ESWL efficacy was better against small, ulcerated, and radiopaque CC, and it had an analgesic effect that might make subsequent surgical excision of CC fragments easier. Ergonomic adaptations are required to facilitate and expand ESWL use in dermatology.

Laparoscopic adenectomy: a novel technique for managing benign prostatic hyperplasia.

The prostatic capsule is opened 3–4 cm transversally according to prostate size. Haemostatic sutures are placed at the 5 and 7 o’clock positions. Coagulation is obtained by bipolar diathermy. For the first three patients the right index finger was introduced through a 2-cm suprapubic incision into the capsule, permitting enucleation of the adenoma as with the open technique (Fig. 3). After closing the incision, CO 2 was again insufflated to control the section of the adenoma at the apex, which is always visible with the laparoscope. For the last two patients, enucleation was entirely under laparoscopic control without using the finger. The specimen was then placed in the lateral prostatic fossa to await removal. A 22 F irrigation catheter is then introduced (Fig. 4) and a running suture of 2–0 polyglactin used to close the prostatic capsule (Fig. 5). A suction drain is placed in the Retzius space by a lateral trocar. The bladder is irrigated as before with a saline solution. At the end of the procedure, the specimen is placed in a laparoscopic bag and extracted through the enlarged umbilical incision.

Protheses péniennes: évaluation multicentrique des pratiques : résultats d’une série de 282 implantations

Resume Objectifs Evaluation multicentrique des pratiques dans le domaine des protheses peniennes a partir de la banque de donnees du Club des Implanteurs de Protheses Peniennes (CIPP). Methode Deux cent quatre vingt deux protheses peniennes, dont 276 gonflables (97,8%), ont ete implantees chez 254 patients entre 1996 et 2005 dans trois centres (1 public et 2 prives). Les donnees pre-operatoires (âge des patients, etiologie et duree de la dysfonction erectile, traitements prealables) et per-operatoires (type d’implant utilise, voie d’abord chirurgicale) ont ete rapportees. Les complications post-operatoires ont ete etudiees et la fonction erectile post-operatoire evaluee par auto-questionnaires (IIEF). Le suivi moyen est de 27,7 mois. Resultats Les protheses peniennes etaient posees en moyenne apres 39,2 mois de dysfonction erectile chez des patients d’âge moyen 58,6 ans. Les etiologies principales etaitent arterielles (35,3%), le diabete (22,8%) et la pro-statectomie radicale (16,5%). Le taux de sepsis post-operatoire etait de 2,2% et celui des dysfonctions mecaniques de 7,5% lors des premieres poses. Les autres complications necessitant une revision chirurgicale (erosion, migration, auto-inflation) etaient de 1,8% lors des premieres poses. Le risque septique etait augmente (7,6%) en cas de diabete (p=0,01). La satisfaction globale post-operatoire etait de 86,7% et le score IIEF evolue de 20,5 ± 11,8 en pre-operatoire a 68,9 ± 5,4 en post-operatoire. Conclusion La prothese penienne, avec un taux de complications faible, avait de hauts scores de satisfaction post-operatoire. Elles n’etaient neanmoins indiquees qu’en cas d’echec des traitements moins invasifs et devaient etre implantees par des operateurs en ayant l’experience. Ces resultats etaient comparables aux grandes series monocentriques internationales.