[Standards, Options, and Recommendations for brachytherapy in patients with prostate cancer: efficacy and toxicity]. / Standards, Options et Recommandations pour la curiethérapie des patients atteints de cancer de la prostate: efficacité et toxicité.

CONTEXT: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery. OBJECTIVES: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project. METHODS: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers. RESULTS: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.

Comparison of the Bard Trak test with voided urine cytology in the diagnosis and follow-up of bladder tumors.

OBJECTIVES: To compare the results of the BTA Trak test with voided urine cytology (VUC) in the diagnosis and follow-up of bladder tumors. PATIENTS AND METHODS: Urine samples were obtained from 53 patients with bladder tumor (77 samples) and 53 patients treated for bladder tumor with no evidence of disease on the basis of cystoscopic evaluation (88 samples). Urine samples were collected prior to cystoscopy. The BTA assay was performed by the BTA Trak test according to the manufacturer's recommendations. A value >14 U/ml was considered abnormal. RESULTS: There was a statistically significant increase in median BTA value with increasing stage of tumor: 11.9, 57.9 and 391.0 U/ml respectively for stages pTa, pT1 and pT2/3 (p<0.0001, Kruskal-Wallis test). There was also a correlation between increasing grade and median BTA values measured at 6.9, 13.1 and 235.0 U/ml in grades 1, 2 and 3 tumors respectively (p<0.0001, Kruskall-Wallis test). The overall sensitivity of the BTA Trak test was 58.4% compared to 46.7% for VUC, a difference of 11.7%, which was statistically significant (McNemar test, p<0.005). The sensitivity of both tests combined was 63.6%. The specificity of the VUC (94.3%) was significantly higher than that of the BTA Traktrade mark (75.0%) (p<0.005, McNemar test). The accuracy of the Bard Trak test (67.3%) was similar to that of VUC (66.9%). CONCLUSION: The BTA Trak test is more sensitive than urinary cytology in the detection of bladder tumors but the improvement involved is insufficient to consider decreasing the frequency of endoscopic examinations in the follow-up of superficial bladder tumor.

[Is it possible to define a threshold for free PSA index that is useful in the daily practice of urology?]. / Est-il possible de définir un seuil de l'index de PSA libre utile en pratique urologique quotidienne?

OBJECTIVES: Retrospective evaluation of the use of the free PSA index before prostatic biopsies. MATERIAL AND METHODS: The authors retrospectively studied the values for total PSA, free PSA, and free PSA index (ratio of free PSA over total PSA expressed as a %) in men with a total PSA between 2 and 10 ng/ml, from a population of 391 men prior to prostatic biopsies. They also isolated a subgroup of patients in whom the free PSA index could have been used as a first-line marker to decide whether or not to perform prostatic biopsies. RESULTS: The mean values for total PSA, free PSA, and free PSA index were compared as a function of the diagnosis, age, and ultrasound prostatic volume. The yields of the various cut-off values for the free PSA index for PSA between 2 and 4 ng/ml, 4 and 10 ng/ml, and 2 and 10 ng/ml with a normal digital rectal examination are reported. Between 2 to 10 ng/ml, at a cut-off value of 30%, 94.1% of cancers would have been detected (sensitivity) and 22% of biopsies would have been avoided, 10 of which would have been useless, i.e. a 30.3% economy of useless biopsies not performed (specificity). At the cut-off value of 15%, less than half of cancers would have been detected (47.1%) and 90.9% of useless biopsies would have been avoided. Biases creating difficulties of interpretation were the assay kits, the reference population, age, storage of sera, and prostatic volume. CONCLUSION: The free PSA index would be a useful first-line parameter in only 12.7% of candidates for prostatic biopsies. The cut-off value of 30%, validated for our assay method, would be able to detect the majority of cancers in men aged 50 to 65 years, while avoiding biopsies in the third of men with no detectable cancer.

[Flow cytometry in cancer of the bladder]. / Cytométrie en flux dans les cancers de la vessie.

We reassessed the use of DNA flow cytometry in bladder cancers on the basis of our research and already published findings. We discuss technical aspects underlying the validity of the results. Currently, the validity of DNA flow cytometry is established by parametric analysis of the DNA content of tumor cells found in the course of multiple biopsies of the tumor. In addition, we examine the results obtained with bladder washings and, in some cases, the results of biopsies of the bladder mucosa which may appear normal under cystoscopy. The complementarity of these examinations appears to be essential. Our experience confirms the results already published, suggesting that the frequency of DNA aneuploidy increases significantly according to the grade and the tumor stage. However, clinical interpretation of DNA flow cytometry results calls for some caution. There is a general consensus not to use these results in the screening of bladder cancers. However, DNA flow cytometry is particularly useful in the follow-up of carcinoma in situ since DNA aneuploidy is almost always present. DNA flow cytometry is also useful in the stratification of superficial grade 2 tumors. Finally, during the follow-up of invasive tumors, the persistence or appearance of DNA aneuploidy may be attributed to therapeutic resistance.

Three-month sustained-release form of triptorelin in patients with advanced prostatic adenocarcinoma: results of an open pharmacodynamic and pharmacokinetic multicenter study.

The pharmacodynamics and the pharmacokinetic characteristics of a new longer-acting formulation containing 11.25 mg of triptorelin (Decapeptyl) to be administered every 3 months were evaluated in 14 patients with advanced prostate carcinoma. After one single injection, the mean time to reach the surgical castration testosterone range is 22 days, and this effective testosterone suppression is maintained for the 3-month therapy. After a first plasma surge (35.70 ng/ml) occurring 2.5 h after injection and a rise between day 17 and day 31 (maximum on day 24: 0.32 ng/ml), the mean triptorelin plasma level is stable (0.06 +/- 0.05 ng/ml) and maintained until day 91. This new formulation was well tolerated both locally and systemically.

Flutamide versus orchidectomy in the treatment of metastatic prostate carcinoma.

PURPOSE: To compare in a randomized clinical trial the therapeutic efficacy of the nonsteroidal antiandrogen flutamide 250 mg tid to testicular androgen suppression by orchidectomy in patients with metastatic prostate cancer. PATIENTS AND METHODS: Between 1989 and 1991, 104 patients aged 74 +/- 8 years with newly diagnosed metastatic prostate cancer, an ECOG performance status 0-2 and no prior hormone manipulation or chemotherapy, were randomized to receive flutamide 250 mg tid (54 patients) or orchidectomy (50 patients). Patients were evaluated at entry and at months 3, 6, 12, 18 and 24. The primary endpoint was duration of progression-free survival, progression being defined as an increase in PSA> 50% over the nadir value at 2 consecutive months or a single PSA rise > 50% over the nadir value with another objective parameter. At progression, the treatment was left to the discretion of the attending urologist. RESULTS: 16 patients (10 flutamide, 6 orchidectomy) are not evaluable. 86 had a minimum follow-up of 36 months, 36/42 and 41/44 have progressed in the orchidectomy and flutamide group with a time of failure of 419 and 496 days (p = 0.32); median time to progression was almost identical in both groups (370 vs. 396 days p = 0.9); overall survival at 69 months irrespective of treatment at relapse was identical in both groups. Side effects were dominated by gynecomastia, hot flushes in both groups, breast tenderness and diarrhea in the flutamide group. Overall, 4 (10%) of the patients in the flutamide group withdrew from therapy because of side effects. The impact of flutamide on sexual potency was not assessed because of the advanced age of the patients. Serum testosterone rose by 50% over baseline level at month 3 to plateau at 25% over baseline level at month 12. CONCLUSION: Although affected by the lack of a clear statistical power due to the small number of patients in each arm, this study shows that in spite of a constant elevation of serum testosterone (25% over baseline) flutamide 250 mg tid may be a reasonable alternative to castration in highly selected patients with well to moderately differentiated low volume metastatic prostate cancer and wishing to avoid the side effects of androgen deprivation, provided they are closely monitored and ready to switch to standard androgen deprivation in the presence of untolerable side effects or suboptimal treatment efficacy as assessed by the inability to achieve a low PSA nadir.

[Clinical assessment of free serum prostate specific antigen (PSA)]. / Evaluation clinique de la mesure de l'antigène spécifique de la prostate (PSA) sous sa forme libre sérique.

The prostate specific antigen (PSA) level represents all of the immunoreactive serum PSA, either free or bound to alpha-1-anti-chymotrypsin. Isolated assay of free PSA has demonstrated a higher free PSA/total PSA ratio in cases of benign prostatic hyperplasia (BPH) than in cases of cancer, suggesting the possible use of this ratio in the detection of prostatic cancer when the PSA level is between 4 and 10 ng/mL. We retrospectively assayed free PSA in 64 cases of localized prostate cancer, 90 cases of BPH before transurethral resection and 59 healthy controls. By comparing the mean values of the 3 populations and the ROC curves, we confirmed the superiority of the free PSA/total PSA ratio over total PSA in the detection of prostatic cancer, but these results, established in a retrospectively constituted population, need to be confirmed by prospective epidemiological studies. Nevertheless, in routine urological practice, we propose that free PSA assay be performed in all men with a PSA level between 4 and 10 ng/mL and a normal prostate on digital rectal examination.

ras, p53 and HPV status in benign and malignant prostate tumors.

To study the role of ras, p53 genes and HPV virus (16 and 18) in the development of prostate cancer, we analyzed tissue sections from 27 patients affected with carcinomas (stages A to D) and from 24 patients with adenomas. Mutations of H, K and N-ras and p53 (exons 2-9) were studied by SSCP and DNA sequencing. Accumulation of p53 protein was studied by immunohistochemistry on tissue sections. Tumors were also analyzed for the presence of HPV16 and -18 sequences by PCR and DNA hybridization with sequence-specific oligonucleotides. No mutation was found in the three ras genes studied, either in carcinomas or adenomas. By SSCP analysis we identified p53 mutations in only 2 of 19 carcinomas studied, both in exon 7. Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+. Among these I presented a p53 mutation. No HPV18 E6 sequence could be detected. Our data show that in prostate tumors from France, mutations of p53 and ras are rare events but that these tumors display detectable HPV16 DNA at a high frequency. The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV16 infection could participate in p53 inactivation by E6.

[Small cell carcinoma of the prostate. Complete remission after chemoradiotherapy: apropos of a case]. / Carcinome de prostate à petites cellules. Rémission complète après chimio-radiothérapie: a propos d'un cas.

The authors report a case of pure small cell carcinoma of the prostate expressing neuroendocrine markers on immunohistochemistry. Treatment consisted of chemotherapy with cisplatin and etoposide combined with regional external beam radiotherapy. The result is encouraging with complete remission 15 months after the diagnosis.

[Is the urodynamic assessment of enuresis in young adults justified?]. / Le bilan urodynamique de l'énurésie de l'adulte jeune est-il justifié?

Primary or secondary nocturnal enuresis in adults (over the age of 15 years) is rare, but is associated with considerable psychosocial repercussions. The aim of this retrospective study was to determine whether urodynamic studies have any predictive value for the efficacy of the treatments proposed in these patients. This study was based on 20 patients (8 females and 12 males) between the ages of 15 and 33 years (mean: 23.75 years), studied between 1982 and 1990 with a mean follow-up of 13.35 months. Enuresis was primary in 12 patients and secondary in 8 patients. 11 patients had already received one or more treatments without success. Patients with clinically obvious neurological disease were excluded from the study. The urodynamic assessment included water cystomanometry, water urethromanometry with a perfused catheter and uroflowmetry. In addition to the investigation of other associated disturbances of micturition, the following complementary investigations were performed: urine culture in every case, IVU and/or cystography (n = 18), cystoscopy (n = 3), renal and vesical ultrasonography (n = 1). The urodynamic assessment was abnormal in 16 out of 20 cases: marked detrusor hyperactivity (n = 15), impaired compliance (n = 6), significant urethral instability (n = 7), isolated premature urge (n = 1). 15 patients presented with diurnal disorders dominated by frequency (n = 13), urgency (n = 9) and urge incontinence (n = 4); detrusor hyperactivity was detected in every case. The abnormalities observed on the urodynamic assessment guided treatment, allowing correction of enuresis in 3/4 of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[The tumorous form of bladder malacoplakia. Apropos of 2 cases]. / Malakoplakie vésicale à forme tumorale. A propos de deux cas.

The authors report two rare cases of neoplastic vesical malakoplakia, one with an enterovesical fistula and the other with extravesical pelvic extension. The symptoms are non-specific and the diagnosis remains histological. Medical treatment, based on the suspected infectious physiopathogenesis of the disease, consists of variable combinations of antibiotics, cholinergics and vitamin C. It must be sufficiently prolonged and conservative in view of its usual efficacy, even in neoplastic forms.

[Pelvic lipomatosis. A case with ureteral and venous obstruction]. / Lipomatose pelvienne. A propos d'un cas avec obstruction urétérale et veineuse.

The authors report a case of pelvic lipomatosis in a 62 year old man associated with venous obstruction (third case reported in the literature), diagnosed after bilateral ureteric obstruction, and review of the literature on this subject. The diagnosis was suggested by the radiological triad of hyperlucency of the pelvis on plain abdominal X-ray, "hot air balloon" appearance of the bladder on IVU and a rigid and ascended rectosigmoid on barium enema, and was confirmed by CT and MRI. Treatment combining corticosteroids and urinary tract disinfection was partially effective. A double J ureteric stent resolved the problem of persistent right ureteric obstruction.

[Substitute bladders]. / Les vessies de remplacement.

Following prostato-cystectomy in men or total cystectomy in women the bladder can be replaced by constructing an intestinal pouch to be connected to the urethra. This bladder replacement reservoir should possess the specific qualities of the natural bladder: it should collect and retain the urine at low pressure, protect the upper urinary tract against reflux and distension, control voluntary micturition at a socially acceptable rhythm and avoid the metabolic disorders due to the reabsorption of urine by the intestinal mucosa. Low pressure reservoirs are the ones most commonly used. They are obtained by opening the ileal or ileocaecal graft along its antimesenteric border and rearranging the intestinal tissue to form a pouch connected to the urethra. Detubulated reservoirs have a capacity and a compliance that are close to those of the urinary bladder. Daytime continence is acquired in the immediate postoperative period, and night-time continence is possible in 60 to 70 per cent of the patients. These are the main advantages of bladder replacement by tubular small intestine. The reservoirs thus constructed have few contractions, but they have not yet proved to be capable of full evacuation in the long term. Intermittent bladder catheterization might well be the price to be paid in the future for an immediate improvement in night-time continence.

[Long-term results of urethrectomy following termino-terminal urethrorrhapy for urethral stenosis. A study of 18 cases]. / Résultats à long terme des urétrectomies suivies d'urétrorraphie termino-terminale pour sténose de l'urètre. Etude de dix-huit cas.

Urethrectomy followed by terminoterminal urethrorraphy is one of the oldest surgical techniques for treating short urethral stenoses, regardless of their location. Eighteen patients managed by this technique were followed-up for at least ten years. Results were satisfactory in four out of every five cases and success was nearly immediate. No delayed deteriorations were seen. These limitations are mainly related to the length of the lesion.

Total androgen blockade with Zoladex plus flutamide vs. Zoladex alone in advanced prostatic carcinoma: interim report of a multicenter, double-blind, placebo-controlled study.

A double-blind, placebo-controlled, randomized, multicenter study was undertaken to investigate the effects of Zoladex plus flutamide vs. Zoladex plus placebo in patients with advanced prostatic cancer. Interim analysis has revealed no differences between the 2 groups in objective or subjective responses at 6 months' follow-up or in overall survival and time to disease progression at 15 months' follow-up.

The usefulness of prostate-specific antigen and prostatic acid phosphatase in clinical practice.

A comparative study was performed on the usefulness of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) in control subjects (69), benign prostatic hypertrophy (BPH) patients (150), and patients with prostatic carcinoma (113) in a urology department. We establish, as others, the greater clinical sensitivity of PSA and its effectiveness as a prognostic tool in the evaluation of prostatic cancer therapy and in the early detection of residual tumor following radical prostatectomy. However, patients are admitted to our department with more severe and complicated benign prostatic pathology and urinary dysfunctions, which decreases the specificity of the PSA test to 30% (N = 2.7 ng/ml). A cutoff threshold of 50 ng/ml becomes necessary to maintain a 90% positive predictive value. The combination of PSA sensitivity (96%) and PAP specificity (95%) enabled a better definition of the high-risk subpopulation among noncancer patients and, in addition, was a help for differential diagnosis, confirmation of advanced stages of prostatic cancer, and selection of low-stage prostatic cancer candidates undergoing radical prostatectomy. Routine serum PSA measurements in the population of patients consulting a urology department will no doubt bring about a new approach to the management of prostate cancer.

[The value of preoperative perineal rehabilitation in radical prostatectomy and replacement entero-cystoplasty. Preliminary results]. / Intérêt de la rééducation périnéale pré-opératoire dans les prostatectomies radicales et les entérocystoplasties de remplacement. Résultats préliminaires.

Radical surgery of the prostate and replacement entero-cystoplasty are associated with varying degrees of risk of diurnal or nocturnal incontinence, which is always poorly tolerated by the patient. In order to reduce this discomfort, perineal reeducation, commenced before the operation, appears to be a valuable aid. A survey of sphincter function easily detects patients at risk and postoperative sphincter disorders can be prevented to a large degree. The authors analyse their preliminary results in 14 patients undergoing radical prostatectomy and in another 10 patients undergoing replacement entero-cystoplasty.

[Prognostic value of cytofluorometry in bladder tumors]. / Intérêt pronostique de la cytofluorométrie dans les tumeurs vésicales.

Bladder lavage fluid was examined using flow-cytometry (FCM) in 112 patients with transitional cell carcinoma seen over 30 months. FCM investigates the entire mucosa, furnishes indications as to the possible existence of dysplasia or carcinoma in situ, and thus provides for a more accurate evaluation of the evolutive potential of the "bladder disease". FCM consists in the automated assay of the DNA content of epithelial cells. The test is positive when "tumorous" diploid or aneuploid cells are demonstrated. The diagnostic sensitivity of FCM is comparable to that of cytologic diagnosis on bladder lavage specimens, but FCM has the additional advantage of detecting those patients at high risk for disease progression by measurement of the DNA index. Grade 1 and 2 tumors are diploid in 70% of patients, against only 14% for grade 3 tumors and carcinomas in situ. Follow up of 25 grade 2 patients and determination of the recurrence index clearly establishes the prognostic significance of the degree of tumorous ploidy. Furthermore, the effectiveness of endovesical chemotherapy can be monitored using FCM measurement of the aneuploidy index.