Michaël Peyromaure

Prebiopsy Magnetic Resonance Imaging and Prostate Cancer Detection: Comparison of Random and Targeted Biopsies

PURPOSE We compared the accuracy of visual targeted biopsies vs computerized transrectal ultrasound-magnetic resonance imaging registration using a rigid (Esaote®, nondeformable) or elastic (Koelis®, deformable) approach. MATERIALS AND METHODS A total of 391 consecutive patients with suspected localized prostate cancer were prospectively included in analysis. All patients underwent prostate magnetic resonance imaging, followed by 10 to 12-core random prostate biopsies. When magnetic resonance imaging detected suspicious findings, targeted biopsy was performed, including visual, rigid system and elastic system targeted biopsies in the first 127 patients, the next 131 and the last 133, respectively. Cancer detection rates were assessed by conditional logistic regression. Targeted biopsies alone and random biopsies were further compared for the amount of tissue sampled and microfocal cancer detection, the latter defined as a single core with 5 mm or less of Gleason 6 cancer. RESULTS Patient characteristics and random biopsy detection rates were similar among the groups. Magnetic resonance imaging detected at least 1 suspicious area in 54 (42%), 78 (59%) and 82 patients (62%) in groups 1, 2 and 3, respectively. The cancer detection rates of rigid and elastic system targeted biopsies were significantly higher than the random biopsy rate (p = 0.0065 and 0.0016, respectively). Visual targeted biopsy did not perform better than random biopsy (p = 0.66). Rigid and elastic system targeted biopsies allowed for decreasing the number of cores and the detection of microfocal cancer, while increasing the detection of high grade cancer. CONCLUSIONS When performed with computerized magnetic resonance imaging-transrectal ultrasound image registration, targeted biopsy alone improved cancer detection over random biopsies, decreased the detection rate of microfocal cancer and increased the detection rate of cancer with a Gleason score of greater than 6.

The value of a second transurethral resection in evaluating patients with bladder tumours.

OBJECTIVES To evaluate the usefulness of a second transurethral resection for superficial and muscle-invasive bladder tumours. METHODS A review of the literature relevant to repeat resection for bladder tumours was conducted using Medline Services. RESULTS Transurethral resection of the bladder has two shortcomings: underestimating clinical stage, and overlooking other lesions. A second transurethral resection, when performed 2-6 weeks after the initial resection, corrects clinical staging errors in 9-49% of cases and detects residual tumour in 26-83% of cases. A second resection is particularly warranted for T1 tumours since 2-28% of them prove to be muscle-invasive, thus requiring a change in management. For muscle-invasive tumours, a second resection may be performed only if bladder sparing is being considered, as it helps to exclude the presence of tumour sites contra-indicating conservative treatment. CONCLUSIONS A second transurethral bladder resection may be warranted for T1 tumours, and for invasive tumours when a bladder preservation is planned.

The management of stress urinary incontinence after radical prostatectomy

Up to 30% of patients complain about urine leakage after radical prostatectomy, but persistent stress incontinence (beyond 1 year) affects <5% of them. This complication is mainly caused by sphincter dysfunction. Some preventive measures have been described to decrease the risk of incontinence after radical prostatectomy, but with conflicting results. The effectiveness of preoperative and early postoperative physiotherapy is controversial. Moreover, while meticulous apical dissection of the prostate significantly improves postoperative continence, the benefit of other surgical techniques, e.g. preserving the bladder neck and the neurovascular bundles, is under debate. The treatment of persistent stress urinary incontinence is mainly based on surgery, as this type of incontinence usually does not respond to physiotherapy and anticholinergic medication. While injection therapy is safe and well tolerated, its effect on postoperative continence is limited and decreases with time. The best results are achieved by implanting an artificial urinary sphincter, but with significant complication and revision rates.

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) .

PAIN AND MORBIDITY OF AN EXTENSIVE PROSTATE 10-BIOPSY PROTOCOL: A PROSPECTIVE STUDY IN 289 PATIENTS

PURPOSE Some studies imply that increasing the number of prostate biopsy cores may improve the cancer detection rate. We performed a prospective study to evaluate pain and morbidity after an extensive transrectal ultrasound guided 10-core biopsy protocol. MATERIALS AND METHODS A total of 289 consecutive men with abnormal digital rectal examination findings and/or increased prostate specific antigen underwent extensive prostate biopsy involving 6 sextant and 4 peripheral biopsies. Each received an information leaflet a few days before the procedure. A single dose of fluoroquinolone and a rectal enema were administered before biopsy. In no case was the procedure performed using anesthesia. Immediately after biopsy patients were asked to complete a self-administered nonvalidated questionnaire evaluating the degree of pain and/or discomfort using a visual analog scale. In another questionnaire they listed the side effects noticed during month 1 after biopsy. RESULTS Although 48% of the 275 men who completed the initial questionnaire reported anxiety before the procedure, 78.8% of them were completely reassured by the information brochure. Of the 275 patients 47.6% described the procedure as painful, including only slightly painful (analog visual scale 3 or less) in 67.9%, while 33.8% described it as uncomfortable but not painful and 18.6% thought that it was neither painful nor uncomfortable. Of the 115 patients who engaged in sexual intercourse during month 1 after the procedure 78.3% noticed hematospermia an average of 10.9 days in duration. Of the 164 men who completed questionnaire 2, 74.4% noticed hematuria an average of 2.7 days in duration, 3.7% noticed pyrexia and 1.2% noticed acute prostatitis. In the 59 patients (36%) who reported delayed perineal pain it was slight in 64.4%, moderate in 30.5% and severe in 5.1%. No patient required hospitalization. CONCLUSIONS Although minor complications are common, the extensive 10-core prostate biopsy protocol is associated with few major complications. The occurrence and intensity of pain and discomfort are in the range reported after the standard 6-core biopsy protocol.

[CCAFU Recommendations 2013: Prostate cancer].

INTRODUCTION The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. METHODS Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. RESULTS Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. CONCLUSION From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined.

Prognostic value of p53 overexpression in T1G3 bladder tumors treated with bacillus Calmette-Guérin therapy.

OBJECTIVES To evaluate the correlation between the overexpression of mutant protein p53 and disease recurrence and progression in patients treated with bacillus Calmette-Guérin (BCG) intravesical therapy for T1G3 bladder cancer. METHODS We analyzed the outcome of 29 consecutive patients treated for T1G3 bladder tumor with transurethral resection. Patients previously treated for a bladder tumor, those who underwent incomplete resection, and those in whom no assessment of the muscle cell layer was possible were excluded from the study. p53 overexpression was determined using monoclonal p53-DO7 antibody, with a 20% cutoff for definition of positivity. After the initial transurethral resection, all patients were treated with Pasteur BCG (75 mg in 50 mL saline), weekly for 6 weeks. The correlation between p53 overexpression and disease recurrence and progression was assessed by the Fisher exact test. RESULTS The median follow-up was 36.7 months (range 1 to 108). Of the 29 patients, 18 (62.1%) were p53 positive and 11 (37.9%) were p53 negative. Both groups were similar according to age, tumoral substage (T1a/T1b), association with carcinoma in situ, multifocality, and length of follow-up. The recurrence rate was 54.4% in the p53-negative group versus 38.9% in the p53-positive group (P = 0.47). The progression rate was 18.2% in the p53-negative group versus 33.3% in the p53-positive group (P = 0.67). CONCLUSIONS These findings suggest that overexpression of p53, as determined immunohistochemically, has no predictive value for recurrence and progression in T1G3 bladder cancers treated with intravesical BCG.

Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation?

PURPOSE We determined whether endorectal multiparametric magnetic resonance imaging at 1.5 Tesla could predict tumor target volume in the perspective of focal therapy of prostate cancer. MATERIALS AND METHODS A total of 84 consecutive patients underwent multiparametric magnetic resonance imaging before radical prostatectomy. The volume of each suspicious area detected on magnetic resonance imaging and of all surgical histological foci was determined by planimetry. We first used each magnetic resonance imaging sequence (T2-weighted, diffusion weighted and dynamic contrast enhanced) and then the sequence showing the largest tumor area (multiparametric volume). Finally, the largest area of any sequence was used to calculate a target volume according to the volume of a cylinder. Agreement between magnetic resonance imaging and pathological findings was assessed by linear regression and residual analysis. RESULTS Histology revealed 99 significant tumors with a volume of greater than 0.2 cc and/or a Gleason score of greater than 6. Of the tumors 16 (16.2%) were undetected by multiparametric magnetic resonance imaging. Linear regression analysis showed that tumor volume estimated by T2-weighted or diffusion weighted imaging correlated significantly with pathological volume (r(2) = 0.82 and 0.83, respectively). Residuals from diffusion weighted imaging volume estimations did not significantly differ from 0. Nevertheless, diffusion weighted imaging underestimated pathological volume in 43 of 87 cases (49%) by a mean of 0.56 cc (range 0.005 to 2.84). Multiparametric and target volumes significantly overestimated pathological volume by a mean of 16% and 44% with underestimation in 28 (32%) and 15 cases (17%), respectively. Volume underestimation was significantly higher for tumor foci less than 0.5 cc. The percent of Gleason grade 4 did not influence tumor volume estimation. CONCLUSIONS Magnetic resonance imaging can detect most significant tumors. However, delineating a target volume may require further adjustment before planning magnetic resonance imaging targeted focal treatment.

AGE DIFFERENCE BETWEEN PATIENT AND PARTNER IS A PREDICTIVE FACTOR OF POTENCY RATE FOLLOWING RADICAL PROSTATECTOMY

Purpose: We evaluated the influence of partner age on postoperative erectile function in patients who underwent bilateral nerve sparing radical prostatectomy for localized prostate cancer.Materials and Methods: The study group was a cohort of 240 consecutive patients treated with radical prostatectomy with a minimum 1-year followup. None had received adjuvant therapy. Evaluation was done by questionnaires mailed to a third party. Potency was defined by erection sufficient for sexual intercourse with vaginal penetration. A total of 200 patients were evaluable.Results: The postoperative potency rate in 189 preoperatively sexually active patients was 59%. On univariate analysis patient age and the age difference between patient and partner were significantly associated with the potency rate following surgery, that is 60.8 and 6.8 years in the preserved potency group and 63.3 and 4.2 years in the impotent group (p <0.001 and p = 0.02, respectively). On multivariate analysis age difference was a predictive fac...

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: a study of 62 patients

OBJECTIVES To determine the predictive factors of prostate-specific antigen (PSA) recurrence after salvage radiotherapy (RT) for biochemical recurrence following radical prostatectomy (RP) to identify patients who may benefit from this treatment. METHODS From June 1992 to January 2002, 62 patients experiencing PSA recurrence after RP were treated with RT at a dose of 65 Gy. No patient received hormonal therapy. PSA recurrence after RT was defined as three consecutive increased PSA measurements. The risk of experiencing PSA recurrence after RT was analyzed according to 10 factors: patient age, pre-RP PSA level, pathologic stage, Gleason score, surgical margin status, PSA nadir after RP, time to PSA recurrence after RP, pre-RT PSA level, PSA nadir after RT, and length of follow-up after RT. RESULTS With a mean follow-up of 44 months (range 3 to 110), 23 patients (37.1%) experienced PSA recurrence after RT. Using univariate analysis, six factors were found to be predictive of PSA recurrence after RT: the length of follow-up after RT (P <0.0001), PSA nadir after RP (P = 0.0004), time to PSA recurrence after RP (P = 0.003), pre-RP PSA level (P = 0.008), Gleason score (P = 0.011), and pre-RT PSA level (P = 0.028). Using multivariate analysis, only the Gleason score (P = 0.015) and length of follow-up after RT (P = 0.02) were found to be predictive of PSA recurrence after RT. A Gleason score greater than 7 was a significant predictor of PSA recurrence after salvage RT (P = 0.04). CONCLUSIONS In our experience, the Gleason score and length of follow-up were the sole independent predictors of PSA recurrence after salvage RT. Our findings suggest that patients with a Gleason score of 7 or less are more likely to benefit from salvage RT after RP and that the durability of the PSA response may be only transient.