Marian Devonec

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.

202 Background: Several studies are in favor of an α/β ratio of less than 3Gy for prostate (P) cancer, encouraging HFR. However, the development of such radiation patterns can only be done if the risk of rectal toxicity is well controlled. The objective of the present study was to evaluate the contribution of an injection of HA between the rectum and the P to reduce the risk of rectal toxicity in a HFR approach. Methods: A phase II study of HFR at 62Gy in 20 fractions (BED = 84Gy; α / β = 1.5Gy) is currently conducted. A transperineal injection of 10cc of HA (NASHA Spacer gel, Q-Med AB, Uppsala, Sweden) is systematically performed, between the rectum and the P, under local anesthesia and under ultrasound guidance. A dosimetric CT scan is performed before (CT1) and after injection (CT2). Patients are treated with a 7 beams IMRT plan, optimized on the CT2. For the first 10 patients included in the study, the same treatment plan was optimized on CT1. The rectum was empty on the 2 CTs and defined from 2cm above the seminal vesicles to 2 cm below the P. The rectal wall was defined by an internal expansion of 5 mm. The volumes of rectum irradiated, with and without HA, were compared on the following dosimetric parameters: maximum dose (D max), dose to 2.5cc (D2.5), 5cc (D5) and 10cc (D10) of rectal wall and volume of rectum receiving 90% (V90), 80% (V80) and 70% (V70) of the prescribed dose of 62Gy. To limit a potential impact of variation of rectal volume between the two CT, all results are given in cc and not in % of volume. Results: The mean P volume was 52.4cc (30cc - 93.8cc) on the CT1 and 52cc (32.5 - 92.7) on the CT2. The injection of HA reduced the mean D max value to the rectal wall of 4.5Gy (57.5Gy vs 62 Gy). The mean values of V90, V80, and V70 are reduced by 69% (1.9cc vs 6.1cc), 46% (4.5cc vs 8.4cc) and 32% (7.4cc vs 10.9cc). Same way, the average values of D2.5, D5 and D10 are reduced by 6.2 Gy (54.6Gy vs 60.8Gy) 9.3Gy (49.0Gy vs 58.3Gy) and 7.8Gy (39.7Gy vs 47.5Gy). Conclusions: In this study, the injection of HA limited the doses to the rectal wall. These results suggest that late toxicities could be significantly reduced. A phase II study is underway to assess the rate of late rectal toxicities when a HFR at 62Gy in 20 fractions is combined with an injection of HA.

Background: Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells.Results: In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells.Conclusions: The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

Sarcoidosis is a multisystemic, non-caseous, benign granulomatous disease of unknown etiology that is sometimes associated with testicular cancer. This association, which does not appear to be accidental, can give rise to diagnostic problems because adenopathies or parenchymatous pulmonary nodules related to sarcoidosis can lead to the presumption of metastatic testicular cancer. The objective of this article was to assess the clinical, histological, and radiological characteristics of the association between sarcoidosis and testicular cancer to help clinicians avoid potentially fatal diagnostic traps and management errors. Literature review. A total of 64 cases of sarcoidosis concomitant with testicular cancer were described in the literature. In more than 50% of the cases (35/64), testicular cancer was diagnosed before sarcoidosis or sarcoid-like reaction. Cancer was diagnosed concomitantly in 31% of cases (20/64). Every anatomopathological type of testicular tumor was described in association with sarcoidosis. Seminoma was the most frequent tumor, occuring in 62% (40/64) of patients. In 80% of the cases (51/64) sarcoidosis regressed spontaneously. Testis cancer may be accompanied by a sarcoid-like reaction or can be associated with real sarcoidosis. The association of testicular cancer with sarcoidosis did not change the therapeutic management of either of these two pathologies. The presence of sarcoidosis does not change the cancer prognosis. Sarcoidosis is a benign disease that resolved favorably and spontaneously in 80% of the cases.

To assess 1) the value of fluorescence immunocytochemistry (uCyt+ test, DiagnoCure Inc., Quebec) in the detection of recurrent bladder tumour after transurethral resection (TUR) and 2) the predictive value of a positive uCyt+ test in patients with negative cystoscopy. This study was based on 132 patients with a mean follow-up of 21.9 weeks after TUR. The initial tumours were pTa G1-2 in 66.7% of cases, and G3 in 28.8% of cases. Cystoscopy, urine cytology (UC) and uCyt+ test data were collected on the day of the first control visit (D0), and the patients were then reviewed at 6 and 12 months. All lesions detected on cystoscopy were biopsed. The mean sensitivity of UC was 47.4% and the mean sensitivity of uCyt+ was 73.7% (84.2% in combination). In patients with negative cystoscopy on D0, a positive uCyt+ test has no predictive value at 6 months. At 12 months, 20.0% of patients with positive UC had relapsed, versus 16.7% of patients with negative UC (p = ns). On the other hand, at 12 months, 50.0% of patients with negative cystoscopy but positive uCyt+ test had relapsed, versus 16.4% of patients with a negative uCyt+ test (p < 0.01). The uCyt+ test allows assessment of the risk of recurrence at I year, while UC alone only has a diagnostic value. These results raise the possibility of combining the tests in order to decrease the frequency of follow-up cystoscopy.

This retrospective study was designed to determine the place of rigid ureteroscopy in the diagnosis of upper urinary tract tumours. 63 patients (45 males and 18 females) with a mean age of 60 years, were investigated by rigid ureteroscopy for suspected upper urinary tract tumour. The Wolf 8-9.8 F ureteroscope was used in the case of suspected upper urinary tract tumour in a context of ureteric obstruction on the IVU in 29 cases, haematuria in 23 cases, a defect on retrograde ureteropyelography in 5 cases, suspicious CT scan in 5 cases and positive cytology with normal cystoscopy in 2 cases. The ureteroscope was able to be advanced as far as the suspicious zone in 89% of cases. The mean operating time was 48 minutes and the mean hospital stay was 3.2 days. Diagnostic rigid ureteroscopy has a Sensitivity of 58% (95% confidence interval CI95: +/- 28), a Specificity of 100%, a Positive Predictive Value of 100%, a Negative Predictive Value of 91% (+/- 7) and a low morbidity (3%). Rigid ureteroscopy does not appear to be the examination of choice for the diagnosis of upper urinary tract tumours, as it cannot investigate the renal pelvis or calices and the ureteroscope cannot always be advanced to the suspicious zone. The flexible ureteroscope now appears to be a more reliable diagnostic tool.