Jean-Luc Moreau

High-intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology.

We discuss the efficacy and safety of high‐intensity focused ultrasound (HIFU) in patients with prostate cancer, to define the best indications for HIFU in daily clinical practice as primary therapy. We searched Medline and Embase for clinical studies evaluating the efficacy and safety of HIFU in prostate cancer (July 2007), and abstracts presented at the 2005–2007 annual meetings of the European Association of Urology and American Urological Association were screened. In all, 37 articles/abstracts were selected. As the data on HIFU as salvage therapy were limited, we focused on HIFU as primary therapy. Studies consisted of case series only. Included patients were ≈70 years old with T1‐T2 N0M0 disease, Gleason Score ≤7, a prostate‐specific antigen (PSA) level of ≤28 ng/mL and a prostate volume of ≤40 mL. Negative biopsy rates with the AblathermTM device (EDAP TMS S.A., Vaulx‐en‐Velin, France) were 64–93%, and a PSA nadir of ≤0.5 ng/mL was achieved in 55–84% of patients. The 5‐year actuarial disease‐free survival rates were 60–70%. The most common complications were stress urinary incontinence, urinary tract infection, urethral/bladder neck stenosis or strictures, and erectile dysfunction. For the Ablatherm device, the rate of complications has been significantly reduced over the years, due to technical improvements in the device and the use of transurethral resection of the prostate before HIFU. In conclusion, HIFU as primary therapy for prostate cancer is indicated in older patients (≥70 years) with T1‐T2 N0M0 disease, a Gleason score of <7, a PSA level of <15 ng/mL and a prostate volume of <40 mL. In these patients HIFU achieves short‐term cancer control, as shown by a high percentage of negative biopsies and significantly reduced PSA levels. The median‐term survival data also seem promising, but long‐term follow‐up studies are needed to further evaluate cancer‐specific and overall survival rates before the indications for primary therapy can be expanded.

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) .

PSA et suivi après traitement du cancer de la prostate

A first serum total PSA assay is recommended during the first three months after treatment. When PSA is detectable, PSA assay should be repeated three months later to confirm this elevation and to estimate the PSA doubling time (PSADT). In the absence of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 ng/ml (or less than 0.07 ng/ml) for the ultrasensitive assay method and less than 0.2 ng/ml for the other methods. In the presence of residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A consensus has been reached to define recurrence as PSA greater than 0.2 ng/ml confirmed on two successive assays. After external beam radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 ng/ml (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 ng or more above the PSA nadir, whether or not it is associated with endocrine therapy. After endocrine therapy, the PSA nadir is correlated with recurrence-free survival. PSA is decreased for a mean of 18 to 24 months followed by a rise in PSA, corresponding to hormone-independence. The time to recurrence or the time to reach the nadir and the PSA doubling time after local therapy with surgery or radiotherapy have a diagnostic value in terms of the site of recurrence, local or metastatic and a prognostic value for survival and response to complementary radiotherapy or endocrine therapy. A PSADT less than eight to 12 months is correlated with a high risk of metastatic recurrence and 10-year mortality. The histological and biochemical characteristics in favour of local recurrence are Gleason score less or equal to seven (3+4), elevation of PSA after a period greater than 12 months and PSADT greater than 10 months. In other cases, recurrence is predominantly metastatic. The risk of demonstrating metastasis in the case of biochemical recurrence after total prostatectomy and before endocrine therapy depends on the PSA level and the PSADT. No consensus has been reached concerning the indication for complementary investigations by bone scan and abdominopelvic CT in patients with biochemical recurrence after treatment of localized cancer without endocrine therapy. However, when PSADT greater than six months, the risk of metastasis is less than 3% even for PSA greater than 30 ng/ml. When PSADT less than six months and PSA greater than 10 ng/ml, the risk of metastasis is close to 50%.

Quality of life of 1276 elderly patients with prostate cancer, starting treatment with a gonadotropin-releasing hormone agonist: results of a French observational study

Abstract This French observational, longitudinal, prospective study described the health-related quality of life (HRQoL) of elderly men (≥75 years old) with prostate cancer after initiating gonadotropin-releasing hormone (GnRH) agonist therapy. At baseline and 3–6 months after baseline, European Organisation for Research and Treatment of Cancer quality of life questionnaire-core 30 (QLQ-C30) and prostate-specific (QLQ-PR25) questionnaires were completed by patients. Data from 1276 patients were analyzed. At baseline, mean (±SD) age was 80 (±4.1) years, 29.1% of patients had Gleason scores ≥8 and 24.9% had metastases. At baseline, increasing age, presence of metastasis and presence of comorbidity had a negative impact on QLQ-C30 and QLQ-PR25 scores. At follow-up, improvement in emotional-functioning (2.8; p < 0.001), social-functioning (1.7; p = 0.011), global HRQoL (1.6; p = 0.029), sleep-disturbance (−2.1; p = 0.011), appetite-loss (−4.0; p < 0.001) and pain (−4.1; p < 0.001) QLQ-C30 scores were observed. In addition, there was a worsening in treatment-related symptom (8.6; p < 0.001), sexual-activity (−5.5; p < 0.001) and sexual-functioning (−22.6; p < 0.001) QLQ-PR25 scores, and an improvement in urinary symptoms (−3.7; p < 0.001) and incontinence aid (−2.9; p = 0.023) QLQ-PR25 scores. This study shows that, apart from the expected impact on sexual functioning domains, HRQoL is not adversely affected by 3–6 months of GnRH agonist therapy in older men with prostate cancer.

Article de revuePSA et suivi après traitement du cancer de la prostatePSA and follow-up after treatment of prostate cancer

A first serum total PSA assay is recommended during the first three months after treatment. When PSA is detectable, PSA assay should be repeated three months later to confirm this elevation and to estimate the PSA doubling time (PSADT). In the absence of residual cancer, PSA becomes undetectable by the first month after total prostatectomy: less than 0.1 ng/ml (or less than 0.07 ng/ml) for the ultrasensitive assay method and less than 0.2 ng/ml for the other methods. In the presence of residual cancer, PSA either does not become undetectable or increases after an initial undetectable period. A consensus has been reached to define recurrence as PSA greater than 0.2 ng/ml confirmed on two successive assays. After external beam radiotherapy, PSA can decrease after a mean interval of one to two years to a value less than 1 ng/ml (predictive of recurrence-free survival). Biochemical recurrence after radiotherapy is defined by an increase of PSA by 2 ng or more above the PSA nadir, whether or not it is associated with endocrine therapy. After endocrine therapy, the PSA nadir is correlated with recurrence-free survival. PSA is decreased for a mean of 18 to 24 months followed by a rise in PSA, corresponding to hormone-independence. The time to recurrence or the time to reach the nadir and the PSA doubling time after local therapy with surgery or radiotherapy have a diagnostic value in terms of the site of recurrence, local or metastatic and a prognostic value for survival and response to complementary radiotherapy or endocrine therapy. A PSADT less than eight to 12 months is correlated with a high risk of metastatic recurrence and 10-year mortality. The histological and biochemical characteristics in favour of local recurrence are Gleason score less or equal to seven (3+4), elevation of PSA after a period greater than 12 months and PSADT greater than 10 months. In other cases, recurrence is predominantly metastatic. The risk of demonstrating metastasis in the case of biochemical recurrence after total prostatectomy and before endocrine therapy depends on the PSA level and the PSADT. No consensus has been reached concerning the indication for complementary investigations by bone scan and abdominopelvic CT in patients with biochemical recurrence after treatment of localized cancer without endocrine therapy. However, when PSADT greater than six months, the risk of metastasis is less than 3% even for PSA greater than 30 ng/ml. When PSADT less than six months and PSA greater than 10 ng/ml, the risk of metastasis is close to 50%.

Selection criteria for initiation and renewal of luteinizing hormone-releasing hormone agonist therapy in patients with prostate cancer: a French prospective observational study.

Objectives: To define the profile of patients with prostate cancer (PCa) receiving a 3-month or 6-month formulation of luteinizing hormone-releasing hormone (LHRH) agonist in France and the reasons for choosing between formulations. Methods: This prospective 1-year observational study included patients with PCa starting LHRH agonist therapy in everyday practice. Reasons for prescription and patient preference were recorded at inclusion, 3 or 6 months, and 12 months. The percentage of patients with a renewed initial prescription was recorded during follow up. Results: A total of 1438 patients with PCa were included. Hormonotherapy was initiated more frequently with a 6-month (n = 903; 62.8%) than with a 3-month formulation (n = 535; 37.2%). The initial prescription was renewed in most patients after 3 or 6 months (86.1%) and 12 months (71%); 170 patients switched from a 3-month to a 6-month formulation during follow up. Presence of metastases influenced initial prescription (odds ratio 0.439; 95% confidence interval 1.095–1.892), with a 3-month formulation more often prescribed than a 6-month formulation to men with metastatic PCa at diagnosis (21.3% versus 15.8%, respectively). The most frequent reasons given by physicians for choosing the 6-month formulation were ‘simplification of therapeutic regimen’ (86.9%) or ‘fewer unnecessary visits’ (46.8%). Similar reasons were given for switching from a 3-month to a 6-month formulation during follow up. The most frequent reasons given by physicians to initiate therapy with a 3-month formulation were ‘usual practice/habit’ (55.5%) or ‘closer patient management’ (46.2%). ‘Closer patient management’ and ‘reassuring effect upon patient’ were the main reasons for switching from a 6-month to a 3-month formulation during follow up. Approximately 80% of patients were satisfied with the formulation they were prescribed and patients’ reasons for preferring one formulation over another were similar to the physicians’ reasons for prescribing these formulations. Conclusions: Slow-release formulations of LHRH agonists are useful therapies for physicians treating patients with PCa and there may be a preference for the 6-month formulation.

Impact métabolique de la suppression androgénique dans le cancer de la prostate

Resume En raison de la faible mortalite imputable au cancer de la prostate, les effets secondaires a long terme des traitements representent un facteur important de la prise en charge des patients. C’est le cas des desordres metaboliques lies aux traitements de suppression androgenique (SA) : augmentation du poids et de la masse graisseuse, resistance a l’insuline pouvant evoluer en diabete et dyslipidemie, d’autant que ces troubles sont deja frequents chez les hommes de plus de 60 ans. A ce jour, il n’y a pas de consensus publie concernant le depistage et le traitement des troubles metaboliques chez les hommes atteints de cancer de la prostate. Il est d’autant plus important de detecter et prendre en charge ces troubles metaboliques qu’ils semblent associes a une plus grande agressivite du cancer. Nous rapportons ici le developpement d’un nouveau questionnaire qui contribuera potentiellement a la prise en charge systematique voire au depistage et au traitement ou a la prevention de ces troubles metaboliques chez les patients atteints d’un cancer de la prostate. En accord avec les revues recentes et sur la base de son experience, notre panel d’experts francais recommande egalement le suivi regulier du taux de glucose a jeun, du profil lipidique et de la pression sanguine chez tous les patients sous SA a long terme, ainsi que des changements d’hygiene de vie (pratique d’une activite physique, habitudes nutritionnelles).

Recommandations pour la prise en charge du cancer de la prostate chez l’homme âgé : un travail du comité de cancérologie de l’association française d’urologie

The increase in life expectancy combined with the increase in the global incidence of cancers will probably results in an increase in the number of cancers observed in the elderly. The increase in the incidence of prostate cancers in geriatric patients (45% of prostate cancers are diagnosed after 75 years old) is in sharp contrast with the lack of strong scientific data on the topic. By the meantime, oncogeriatrics has been developing for some years now under the guidance of the International Society of Oncogeriatrics. Such an approach aims at palliating the low quality of care of cancers in geriatric patients. The reasons for the low quality of care come from the characteristics of these patients and from the training of the care providers. The authors recall the principles of oncogeriatric evaluation and the classification of patients as it is actually proposed. They describe the main treatments and their results in the geriatric population and they describe the decision process concerning the choice of the treatment. They also suggest some guidelines on the diagnosis of prostate cancer, evaluation of the patients and the treatments of the disease in the elderly. Prostate cancer is almost the perfect model for oncogeriatrics. Urologists should remain the corner stone of its management, whatever the age of their patient.

La prostate : Identification des attentes du médecin généraliste. Une enquête qualitative. Association Française d’Urologie (AFU) - IPSOS

Resume Introduction L’information sur les pathologies de la prostate, incluant le cancer de la prostate, est soutenue par l’Association Francaise d’Urologie (AFU) depuis plusieurs annees mais se developpe lentement en France. En 2005, une premiere communication etait consacree au public masculin et avait identifie les raisons de son fatalisme, et paradoxalement, pourquoi la prostate incarne la vulnerabilite de son capital sexuel. Dans une seconde phase, cet article presente les resultats d’une etude complementaire conduite aupres de medecins generalistes ayant pour but d’identifier leurs attentes et les leviers les plus adaptes pour favoriser le depistage. Materiel et Methode La societe Ipsos a developpe un protocole qualitatif Krisis™ realisee en octobre 2005 (apres la premiere journee nationale de la prostate du 15 septembre 2005). Trois groupes de medecins generalistes ont ete constitues : des medecins tres actifs en matiere de depistage, des medecins mal a l’aise avec ce probleme ou des medecins s’en remettant systematiquement aux Urologues. Resultats Les pathologies prostatiques abordees en consultation dependaient de l’aisance du medecin ce qui est liee a sa formation et ses liens avec les urologues. Pour entamer la question du depistage, les generalistes impliques posaient des questions simples a propos de pratiques quotidiennes sans crainte d’etre ludiques ou de s’appuyer sur la mediatisation de la pathologie. Le toucher rectal apparaissait comme un des elements cliniques importants mais pas toujours facile a realiser. Le PSA apparaissait comme un examen pas toujours approprie et caracterise par un deficit d’informations sur les conditions de sa prescription, son utilite et sa pertinence par rapport au depistage. L’echographie pouvait etre une astuce pour alerter le patient sans dramatiser et faire faire le toucher rectal par un Urologue. Les medecins genera listes femmes prefeaient le PSA et l’echographie. Les medecins interroges attenaient une mediatisation des pathologies de la prostate, une grande interactivite avec les urologues et des documents, des brochures a mettre en salle d’attente pour relayer les messages. Conclusion Les Medecins generalistes avaient besoin que leurs instances, les specialistes et les institutions de sante publique developpent et mediatisent l’andrologie au meme titre que la gynecologie. Les Urologues ont un role majeur d’accompagnement par le biais de conferences, enseignements postuniversitaires ou par des invitations initiees par l’AFU.

Diagnostic et prise en charge des événements indésirables sévères survenant au décours des instillations endovésicales de BCG pour le traitement des tumeurs de vessie n’infiltrant pas le muscle (TVNIM)

BCG therapy, which is the standard treatment for non-muscle invasive bladder tumours with high risk of recurrence and progression, has potential life-threatening adverse effects (AEs). Rapid deterioration of general condition in a patient with history of bladder tumour should question about an ongoing treatment with BCG and specify the date of the last instillation. Trauma during catheterization and untreated concomitant urinary infection upon instillations are risk factors of severe AEs. In emergency, the diagnosis of severe AEs of BCG therapy is only based on the medical questioning with the notion of current BCG treatment and risk-bearing event upon instillation. Management of AEs is related to their pathophysiological mechanisms and relies on a combination of antibiotics against BCG, the symptomatic treatment, and corticosteroid therapy which has shown to improve patient outcomes.