What is the effect of MRI with targeted biopsies on the rate of patients discontinuing active surveillance? A reflection of the use of MRI in the PRIAS study.

BACKGROUND: The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification. METHODS: Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation. RESULTS: In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable. CONCLUSIONS: Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted.

[Local consultations by specialists in urology: an answer to patients' expectations and dwindling physician numbers?]. / Les consultations avancées d'urologie peuvent-elles être une réponse satisfaisante aux attentes des patients et au problème de la démographie médicale?

OBJECTIVE: To analyze patients' views with regards to local consultations given by specialists in urology and to an offer of pre- and postoperative visits in the local general hospital with surgical interventions taking place at the university hospital. MATERIALS AND METHODS: An opinion survey by mail questionnaire was carried out in all 473 patients who had had a consultation with a specialist in two local general hospitals between November 2009 and April 2010. RESULTS: Response rate was 74%. Mean patient age was 65.5 ± 12 years [range, 20-90]. The reason for the consultation was cancer-related in 31.2% of patients. The majority (89%) made the journey to hospital under their own steam and would have had to travel a 4 times greater distance if the consultation with the specialist had taken place at the university hospital. Overall, 54.6% of patients were willing to travel 20 km further to see a specialist and 76.5% were willing to travel 20 km further for a surgical intervention. Virtually all of the patients (>99%) saw benefits to local consultations given by specialists. The offer of a consultation at the general hospital and intervention at the university hospital met with the approval of 60.8% patients and 56.3% had already experimented this offer. CONCLUSION: Local consultations by specialists might be an answer to demographic issues in France, that is, to the small number of urologists practicing in general hospitals.

[Bacillus Calmette-Guerin maintenance treatment in non-invasive bladder tumors: 1 year follow-up results of multicenter URO-BCG-4 trial]. / Traitement d'entretien par BCG-thérapie des tumeurs de vessie n'infiltrant pas le muscle (TVNIM): résultats à un an de l'étude multicentrique URO-BCG-4.

INTRODUCTION: Intravesical instillations of BCG remains the gold standard for intermediate and high risk NMIBC management. Maintenance treatment is recommended, however, the frequency of side effects responsible for the discontinuation of maintenance therapy over four out of five patients before the third year suggest a reduction or even spacing instillations. The objective of the study URO-BCG-4 was the evaluation of a new maintenance schedule by intravesical instillations of BCG combined reduced dose (third dose) and a decrease number of instillations per cycle (two or three). MATERIAL AND METHODS: Multicenter study of the French Association Oncologic Committee (12 university hospital centers), randomized, prospective, comparing reference diagram of BCG maintenance therapy one third of usual dose (group I) to a regimen combining third dose and decrease the number of instillations per cycle (two instead of three) (group II). We present the preliminary results at 1year of this Program of Clinical Research (CHU Rouen Promoter 2003-081). RESULTS: The rate of recurrence was respectively 9 and 7% (P=0.678) in groups I and II. The rate of tumor progression are 3 and 2.8% in groups I and II (P=1). Tolerance of intravesical instillations of BCG scored according to the WHO classification (Geneva 1979) was similar in the two groups. CONCLUSION: The decrease in the BCG dose (third dose) and the changes in the number and rate of instillations did not alter free tumor recurrence survival. The toxicity of intravesical instillations of BCG was identical in both groups. The use of the WHO classification has shown its limitations in the study of side effects of BCG as too complex and often not exhaustive. The rate of increase muscle was comparable in the two groups; however, a larger clinical experience is required.

[Androgen deprivation therapy for prostate cancer and osteoporotic risk]. / Suppression androgénique dans le cancer de la prostate et risque ostéoporotique.

Androgen deprivation therapy represents an important part of the management of prostate cancer. However, epidemiological data have shown that it is a well-established cause of osteoporosis and increased risk of fracture. So far no consensus guidelines have been published regarding the screening and treatment of osteoporosis in men with prostate cancer. Here we report the design of a new questionnaire, derived from the FRAX(®) ("Fracture Risk Assessment Tool") algorithm, to evaluate the risk of fracture in those patients. In accordance with recent reviews and on the basis of their experience, our French board of experts recommends systematic screening for osteoporosis with dual energy x- ray absorptiometry scans, practice of exercise and calcium and vitamin D supplementation, and selective treatment with bisphosphonates in men at greatest osteoporotic risk.

Andropause (androgen deficiency of the aging male): diagnosis and management.

Androgen deficiency of the aging male is a pathological syndrome and should not be viewed simply as a stage in physiological aging. It is often overlooked despite evidence for a deleterious impact on many physiological processes and on quality of life. Its identification should be part of the routine practice of physicians in charge of this population, in particular general practitioners and specialists treating associated comorbidities (e.g. metabolic syndrome, diabetes, cardiovascular disorders) or sexual dysfunction. The consultant urologist has a key role to play in prostate surveillance before and during treatment. Treatment is often simple with few side-effects. However, long-term benefits and side effects need to be investigated in prospective studies.

[Endothelin-1 and receptor A: predictive value for biochemical relapse on patients with advanced and metastatic prostate cancer]. / Endothéline-1 et récepteur A: valeur pronostique pour la reprise évolutive biologique dans l'adénocarcinome de prostate localement avancé et métastatique ganglionnaire.

INTRODUCTION: Pathological endothelin axis is known to be involved in prostate cancer progression. Our study evaluates immunohistochemical expression of ET-1 and ET-AR on prostate biopsy specimen and the predictive value for biochemical relapse on patients with advanced and metastatic cancer. We also evaluated the impact of ET-1 and ET-AR expression on local progression and metastatic bone progression for these patients. PATIENTS AND METHOD: From 1992 to June 2009, 44 patients with clinical T3 stage and metastatic lymph nodes were included. PSA levels, Gleason score in biopsy cores, number of invaded lymph nodes, the existence of nodular capsule transgression and hormonal treatment given to the patient, were analyzed. Biopsy cores were submitted to immunohistochemical study of the expression of ET-1 and ET-AR. Semi-quantitative ET-1 and ET-AR staining assessment was always realised by the same pathologist. RESULTS: The average age of the cohort was 65.6 (standard deviation 6.3), median PSA level was 52.8 ng /ml (3-227), median time of follow-up was 70 months (6-144). Biochemical relapse was observed in 62.8%. Statistically significant stronger ET-1 expression was observed in biopsies of patients with a biochemical relapse (p=0.014). Eighty percent of patients with a biochemical relapse had a high level of ET-AR expression, but no statistical significance has been shown (p=0.109). The relative risk for progression under hormonal therapy was 1.9 in case of high level of ET-1 expression and biochemical relapse was confirmed 8 months earlier in average. High level of ET-AR expression on biopsy cores may indicate earlier local progression and metastatic bone progression but there were no statistical proof. CONCLUSION: In our study, the strength of ET-1 expression in prostate cancer biopsy cores is a prognostic factor of biochemical relapse for cT3 stage patients with metastatic lymph nodes. We have not been able to prove that ET-1 is an independent prognostic factor. A high level of ET-AR expression on prostate biopsy cores is not, in our study, a prognosis factor for predicting the biochemical relapse.

[Active surveillance for localized prostate cancer]. / Place de la surveillance active dans le cancer de la prostate à faible risque de progression.

Active surveillance as an alternative approach to immediate curative treatment is demonstrated for an increasing number of patients with low risk prostate cancer. Optimization of selection and surveillance criteria to guarantee a low risk issue to patients are discussed in this review. They lead to consider active surveillance as an option rather than a standard of care for patients ideally included in clinical research protocols.

Erectile dysfunction and sexual health after radical prostatectomy: impact of sexual motivation.

The life expectancy of patients with localized prostate cancer at treatment initiation has increased, and post-treatment quality of life has become a key issue. The aim of this study is to assess the impact of Radical prostatectomy (RP) on patients' sexual health and satisfaction according to sexual motivation using a self-administered questionnaire completed by two groups of RP patients, with high or lower levels of sexual motivation. A total of 63 consecutive patients were included (mean age, 63.9 years), of whom 74.6% were being treated for erectile dysfunction (ED). After RP, patients reported lower sexual desire (52.4%), reduced intercourse frequency (79.4%), anorgasmia (39.7%), less satisfying orgasm (38.1%), climacturia (25.4%), greater distress (68.3%) and/or lower partner satisfaction (56.5%). Among the most sexually motivated patients, 76.0% reported loss of masculine identity, 52% loss of self-esteem and 36.0% anxiety about performance. These rates were lower among less motivated patients (52.6, 28.9, and 18.4%, respectively). Mean overall satisfaction score was 4.8 ± 2.9. The score was significantly lowered in motivated than less motivated patients (3.4 vs 5.8) (P = 0.001). In conclusion, RP adversely affected erectile and orgasmic functions but also sexual desire, self-esteem and masculinity. The more motivated patients experienced greater distress and were less satisfied.

[Modification of sexual desire and orgasm after radical prostatectomy for prostate cancer]. / Modification de la libido et de l'orgasme après prostatectomie totale.

OBJECTIVES: To assess the impact of RP on patients' sexual desire and orgasm. MATERIAL AND METHODS: Prospective, cross-sectional survey using a 16-item self-administered questionnaire. We assessed relevant domains of male sexual function (erectile function, sexual desire, and orgasm), psychological impact and treatment of ED. RESULTS: A total of 63 consecutive patients after RP were included (mean age: 63.9). Median time between questionnaire and RP was 26.8 months (range 6-67). After RP, 74.6 % of patients used ED treatments. Lower sexual desire and intercourse frequency were reported in respectively 52.4 and 79.4 %. Orgasm was modified in most patients: 39.7 % described loss of orgasm and 38.1 % reported decreased intensity. Involuntary loss of urine at orgasm (climacturia) was reported in 25.4 %. Negative psychological impact was reported in 68.3 % (loss of self-esteem, loss of masculinity, anxiety). CONCLUSIONS: RP adversely affected erectile and orgasmic functions but also sexual desire, self-esteem and masculinity despite treatments. Candidates for RP should be aware of ED but also of other postoperative sexual dysfunctions.

Medium-term follow-up of plaque incision and porcine small intestinal submucosal grafting for Peyronie's disease.

The best surgical option for the management of severe cases of Peyronie's disease is currently a matter of debate. To determine medium-term outcomes and complications after treatment of severe Peyronie's disease by porcine small intestinal submucosa (SIS) grafts, we retrospectively reviewed 33 consecutive plaque incisions followed by 4-ply SIS grafting in 28 patients (2002-2009). Postoperative complications, penile length preservation, de novo ED, penile curvature correction and curvature recurrence rates were recorded. Median patient age was 54 years (38-69 years). Median preoperative curvature was 90° (30-90°) (stable for at least 6 months). Six patients (21%) had preoperative ED. There were few postoperative complications (no cases of infection, haematoma (n=2), penile hypoesthesia (n=1), patch rejection and migration (n=1)). Subjective penile shortening and de novo ED were observed in 7 (25%) and 3 (11%) patients, respectively. The success rate for the procedure (straight penis or curvature ≤20° and ability to have intercourse) was 67% (22/33). Four patients achieved curvature correction after a repeat procedure with a new SIS graft. Eleven patients experienced recurrence within 3 months of surgery. After a median follow-up of 9 months (3-94), 22 patients (79%) had a satisfactory curvature correction.

[Prostate biopsies endothelin-1 expression: pt3a stage prognostic factor?]. / Expression immunohistochimique de l'endothéline-1 sur biopsies prostatiques : marqueur pronostique d'adénocarcinome localement avancé ?

AIM: The study evaluated the immunohistochemistry expression of endothelin-1 (ET-1) by prostate cancer (PCa) in prostate biopsies as an extracapsular stage (pT3a) prognostic factor. MATERIAL AND METHOD: Sixty-eight radical prostatectomies (RP) were performed for clinically localised PCa (35 pT2 and 33 pT3a according to the 2002 pTNM classification). Age, digital rectal examination, initial PSA, biopsy Gleason score, positive biopsies ratio, specimen Gleason score, biopsy and RP specimen perineural neoplasic invasion, PCa DNA ploidy, PCa Ki-67 DNA image cytometry and biopsy and RP specimen ET-1 immunohistochemistry expression for both group were compared. Semi-quantitative ET-1 staining assessment was realised by the same pathologist. RESULTS: pT3a group initial PSA was higher (p=0.032). No statistically difference was noticed between pT2 and pT3a groups for positive biopsies ratio, biopsy perineural neoplastic invasion and biopsy DNA ploidy determination. Biopsy Gleason score > or =7 was predictive of a pT3a stage (p=0.03). Statistically higher intensity of ET-1 PCa expression was observed in biopsies and specimens in pT3a group than in pT2 group (p<0.001 and p=0.01). In multivariate analysis, biopsy ET-1 PCa expression was an independent risk factor of pT3a stage with specificity 79 %, sensibility 69 %, predictive positive value 77 % and negative positive value 72 %. Combined with initial PSA > or =7, values were respectively 100 %, 76.9 %, 100 % and 57.1 %. CONCLUSION: Endothelin-1 (ET-1) prostate cancer biopsy expression in our study was an independent prognostic factor of extracapsular stage (pT3a). Further studies will assess the relevance of ET-1 expression study in clinically localised PCa for active surveillance, curative treatment or targeted adjuvant therapy management.

[Androgen deprivation therapy in locally advanced prostate cancer]. / Cancer de la prostate localement avancé et hormonothérapie.

In case of biochemical recurrence after radical prostatectomy, hormonal treatments are equally efficient. Early hormonal treatment after biochemical recurrence reduces specific mortality, local and metastatic progression. In locally advanced prostate cancer, adjuvant radiation therapy after biochemical recurrence reduces local and metastatic recurrence. Withdrawal of the steroid hormone should be the first maneuver after primary hormonal therapy failure. Second generation anti-androgens (abiraterone and MDV 3100) should be released soon. These new hormonal agents are in clinical trials and show promising activity in patients with CRPC.

Transrectal high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer: review of technical incidents and morbidity after 5 years of use.

The objective of this study was to report on technical incidents and early and late complications occurring in high-intensity focused ultrasound (HIFU) treatment of patients with localized prostate cancer. We performed a retrospective review of patients who were treated by Ablatherm at our centre. We recorded all technical incidents, treatment discontinuations and early (<1 month) and late complications. A total of 74 HIFU procedures were performed in 65 patients (55 first-line HIFU treatments and 10 cases of salvage therapy after radiotherapy) over a 5-year period. Median follow-up was 41 months (10-64 months). All the procedures were well tolerated and no intra- or peri-operative deaths occurred. Six technical incidents in the overall population (8.1%) led to discontinuation of the procedure. The early complication rate in patients undergoing first-line HIFU was 36.4%: urinary retention (20%), dysuria (5.4%), urinary infection (3.6%), haematuria (3.6%) and urethral stenosis (3.6%). The late complication rate was 12.7%: urethral stenosis (9%) and dysuria (3.6%). There were no cases of rectourethral fistula. The long-term urinary incontinence rate was 20% and the de novo erectile dysfunction rate was 77.1%. Nine complications (16.4%) required surgical management. The overall complication rate was 49%. Ablatherm is a reliable technique with a relatively high complication rate. However, most complications were minor and required surgical management in a few cases only. Our results confirm that all patients who are offered HIFU treatment should be properly informed of the risks, in particular with regard to continence and sexual function.

[Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives]. / Gènes de fusion et cancer de la prostate. De la découverte à la valeur pronostique et aux perspectives thérapeutiques.

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the prostate cancer tumorigenesis. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancer makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype, which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

Preventing graft thrombosis after renal transplantation: a multicenter survey of clinical practice.

BACKGROUND: Renal allograft vascular thrombosis is a complication that often results in graft loss. Since there are no guidelines on immediate postoperative thromboprophylaxis, we performed a telephone survey of clinical practice in all renal transplantation centers in France. METHODS: Each center considered 4 cases relating to renal transplant candidates on dialysis with an increasing risk of thrombosis: Case 1: patient with no identified risk factors; Case 2: patient with an earlier incidence of deep vein thrombosis; Case 3: patient with ischemic heart disease on antiplatelet therapy; Case 4: patient with atrial fibrillation taking a vitamin K antagonist (VKA) with lupus nephritis syndrome. RESULTS: The treatments proposed by the centers (%) were: Case 1: No anticoagulation therapy (57.1%), calcium heparin at prophylactic doses (P-dose) (40%), or unfractionated heparin (UFH); (P-dose; 2.9%). Case 2: No anticoagulation therapy (34.3%), calcium heparin (P-dose; 51.4%), or UFH (P-dose; 5.7%). Case 3: (A) Interruption of aspirin (65.7%), and either no anticoagulation therapy (21.7%) or substitution of aspirin by calcium heparin (P-dose; 56.6%) or by UFH (P-dose; 8.7%). (B) No interruption of aspirin (34.3%), and either no additional prophylaxis (58.3%) or calcium heparin (P-dose; 33.3%). Case 4: Interruption of VKA (100%), and UFH at a curative dose (68.6%), UFH (P-dose; 14.3%), or calcium heparin (P-dose; 11.4%). CONCLUSIONS: Practices varied widely in the absence of studies of sufficiently high power. There is a need for a preoperative classification of thrombotic and hemorrhagic risk among renal transplant candidates and for consensus guidelines.

[Anticoagulation after renal transplantation: a multicenter survey on clinical practice]. / Quelle thromboprophylaxie après transplantation rénale ? Enquête sur la prévention des thromboses du greffon en France.

OBJECTIVES: Graft thrombosis is a major complication of transplantation. However, there are no recommendation on immediate postoperative thromboprophylaxis after kidney transplantation. We recorded clinical practices in France. MATERIAL AND METHODS: In 29 transplantation centres, four case studies were submitted to the medical kidney transplantation referent (compatible graft from cadaveric donor, without perioperative complication). N(o) 1: Man, 27-years-old, IgA glomerulonephritis, without history of hypercoagulability or cardiovascular risk factor. Hemodialysis since 12months. N(o) 2: Man, 53-years-old, with history of deep venous thrombosis after cholecystectomy 15years before. Membranous nephropathy. Hemodialysis since 10months. N(o) 3: Man, 58-years-old, with history of myocardial infarction. On aspirin therapy. Nephroangiosclerosis and diabetic nephropathy. Peritoneal dialysis since 6months. N(o) 4: Woman, 63-years-old. Atrial fibrillation on vitamin K antagonists therapy. Lupus nephritis without antiphospholipid syndrome. Hemodialysis since 12months. RESULTS: N(o) 1: No anticoagulation therapy (62%), calcium heparin at prophylactic doses (34.5%). N(o) 2: No anticoagulation therapy (38%), calcium heparin at prophylactic doses (44.8%). N(o) 3: 62% interrupted aspirin of whom 22% without any immediate anticoagulation and 55% replaced aspirin with calcium heparin at prophylactic doses. Thirty-eight percent carried on with aspirin of whom 63.6% without other prophylaxis and 27.3% in association with calcium heparin at prophylactic doses. N(o) 4: Unfractionned heparin at curative dose (62%), unfractionned heparin at prophylactic doses (17.2%), calcium heparin at prophylactic doses (13.8%). CONCLUSION: Postoperative anticoagulation after renal transplantation is established as a local dogma rather than evidence-based medicine. Guideline recommendations and standardized protocols for the use of anticoagulation after kidney transplantation should be developed.