Prognostic value of uPA, PAI-1, and DNA content in adult renal cell carcinoma.

OBJECTIVES: To examine whether urokinase-type plasminogen activator (uPA) and type 1 plasminogen inhibitor (PAI-1), DNA ploidy, and S-phase fraction (SPF) add supplementary prognostic information relative to stage and Fuhrman's grade in renal cell carcinoma. METHODS: A total of 100 patients with primary renal adenocarcinoma treated by nephrectomy were followed up for a median of 42 months. Of the 100 patients, 78 with Stage M0N0-Nx tumors were studied by multivariate analysis. The study population was dichotomized on the basis of the median cytosolic uPA and PAI-1 concentrations (30 pg/mg protein and 12.7 ng/mg protein, respectively). DNA content was measured by flow cytometry (FCM) on multiple tumor samples from each patient. DNA aneuploidy was observed in 67% of cases. The SPF was calculated for aneuploid samples. RESULTS: An FCM classification based on a combination of DNA content and SPF was obtained. High-risk patients were those with aneuploid tumors and high SPF values (greater than 1.7%) and included 23% of patients with M0N0-Nx tumors. Cytosolic uPA and PAI-1 levels were not predictive of metastasis. The stage, grade, SPF, and FCM classification were statistically significant prognostic factors in the univariate analysis, in both the overall population and the M0N0-Nx subgroup. In multivariate analysis, tumor grade and the FCM classification were the only independent predictors of disease-free survival (P = 0.018 and P = 0.046, respectively). CONCLUSIONS: We defined a group of M0N0-Nx patients with aneuploid tumors and high SPF values who are at a high risk of metastasis and who may benefit from closer long-term follow-up.

Improved detection of urothelial carcinomas with fluorescence immunocytochemistry (uCyt+ assay) and urinary cytology: results of a French Prospective Multicenter Study.

The aim of the study was to assess the sensitivity and specificity of fluorescence immunocytochemistry (uCyt+ assay) as combined with urinary cytology for detection of primary and recurrent urothelial carcinomas. We analyzed 694 urinary samples from 236 new symptomatic patients and 458 patients followed after transurethral resection (TUR) for bladder tumor. Lesions suspicious for cancer at cystoscopy were sampled by biopsies or TUR. Sensitivity and specificity of tests were calculated using cystoscopy and histopathology, whether or not combined as gold standards. In new symptomatic patients, sensitivity of uCyt+ was 40%, 88.2%, and 76.7%, whereas that of urinary cytology was 30%, 70.6%, and 83.3%, respectively, in G1, G2, and G3 tumors. In follow-up cases, sensitivity of uCyt+ was 61.9%, 66.7%, and 76.9%, whereas that of urinary cytology was 38.1%, 58.3%, and 64.1%, respectively, in G1, G2, and G3 tumors. The combination of uCyt+ and urinary cytology significantly increased mean sensitivity in newly diagnosed cases (86.4% versus 71.2% with urinary cytology only, p < 0.05), as well as in patients followed after TUR (79.3% versus 55.2%, p < 0.001). Specificity of uCyt+ and urinary cytology was identical in new patients (83.3%) and was 81.9% and 86.2%, respectively, in patients followed after TUR. In patients with negative cystoscopy, positive uCyt+ tests had a strong predictive value for tumor recurrence at 1 year (47.0% versus 11.9% in patients with negative assay, p < 0.01). We conclude that combining uCyt+ with urinary cytology improves the detection of urothelial carcinomas as well in patients with symptoms suggesting bladder cancer as in those followed after treatment.

[Biochemical monitoring of prostate cancer treated exclusively by radiotherapy: prognostic value of pretreatment PSA, PSA nadir and PSA half-life]. / Suivi biologique du cancer de la prostate traité par radiothérapie exclusive: valeur pronostique du PSA pré-thérapeutique, du PSA Nadir et de la demi-vie du PSA.

OBJECTIVES: Retrospective evaluation of the prognostic value of pretreatment PSA, PSA nadir and PSA half-life compared to grade and stage after treatment of prostate cancer by radiotherapy. PATIENTS AND METHODS: 122 patients (19 T1 (15.6%), 31 T2a (25.4%), 26 T2b (21.3%), 20 T3a (16.4%), 19 T3b (15.6%), 7 Tx (5.7%)) treated by exclusive radiotherapy were studied with a median follow-up of 75.4 months. Treatment consisted of high energy irradiation to the prostate for 31 patients (25.4%) and to the pelvis and prostate for 91 patients (74.6%). PSA was assayed retrospectively. The influence of various parameters on the absence of laboratory failure, defined according to the ASTRO criteria, and on overall survival was studied by univariate and multivariate analysis with a Cox model. RESULTS: 29.5% of patients did not develop any biochemical recurrence after a mean follow-up of 82 months, while biochemical recurrence occurred in 70.5% of patients after a mean interval of 5 months. Among these patients, 28 (33%) developed clinical recurrence after a mean interval of 26 months (4 to 80 months) leading to death in 17 cases. The modalities of irradiation and pretreatment PSA had no influence on the prognosis. The median PSA nadir of patients without recurrence was 0.24 ng/ml. The recurrence rate was lower for a PSA nadir less than 0.5 ng/ml for biochemical recurrence (45.5% vs 86.8%) (p < 0.0001) and clinical recurrence (9.1% vs 31.6%) (p < 0.05). On multivariate analysis, the PSA nadir (p = 0.009), PSA half-life (p < 0.001) and Gleason score (p = 0.004) were prognostic factors influencing survival, while PSA nadir was the only prognostic factor for biochemical recurrence (p = 0.001). Classification of patients into two groups with a significantly different prognosis according to the presence or absence of at least two favourable prognostic factors (PSA nadir less than 0.5 ng/ml, Gleason score less than 7, PSA half-life greater than 6 months) showed that the 9-year mortality rate was twofold higher in the poor prognosis group than in the good prognosis group (85.5% versus 38.6%). CONCLUSION: A nadir PSA level less than 0.5 ng/ml, a PSA half-life greater than 6 months and a Gleason score less than 7 were predictive of a low risk of biochemical recurrence and prolonged survival after treatment by exclusive radiotherapy, in our patients.