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168 Abstracts

  • Introduction & Objectives

    Prostate cancer treatment is shifting from radical to focal therapy. Instant tumor visualization on a microscopic level is crucial for clinical application of focal therapy. Optical Coherence Tomography (OCT) produces instant tissue visualization on a µm scale. OCT also provides the attenuation as a measure of tissue organization. The objective is to correlate qualitative and quantitative OCT analysis with histopathology.

    Material & Methods

    Twenty prostates were analyzed by needle based OCT after radical prostatectomy. For precise correlation, whole mount histology slides were cut through the OCT trajectory. OCT images were classified in one of eight histological categories (RvK). Two reviewers (AS & BM) independently performed assessments of the OCT images into these categories. Sensitivity and specificity for detection of malignancy on OCT were calculated. Quantitative attenuation coefficient was found to discriminate stroma and malignant tissue. Figure: Correlation of histology and OCT: The arrows in A, B & C indicate the same atrophic cyst. A: Digitized H&E stained whole mount slide with tissue annotation. Both OCT measurement trajectories are visible. B: An OCT scan at the location of the atrophic cyst. C: The longitudinal section of the OCT scan that corresponds with the upper OCT measurement trajectory shown on A.



    Results

    Visual analyses showed that OCT can reliably differentiate between fat, cystic and regular atrophy and benign glands. Differentiation of benign stroma and inflammation and also malignancy Gleason 3 and 4 is more difficult. Sensitivity and specificity for detection of malignancy on OCT were calculated at 77% and 84%. Quantitative analysis by means of the attenuation coefficient for differentiation between stroma and malignancy showed no significant difference (4.39 mm-1 vs. 5.31 mm-1).

    Conclusions

    One to one correlation of histology and OCT helps us to understand what we see and measure on OCT. Visual malignancy detection shows reasonable sensitivity and specificity. Our future studies focus on improving discrimination of malignancy with OCT for example by combining an extra imaging modality.

  • Introduction & Objectives

    Local staging of Prostate Cancer (PCa) has a crucial role in decision-making process about resection or preservation of Neurovascular Bundles (NVB) during radical prostatectomy. The clinical relevance of multiparametric Magnetic Resonance Imaging (mpMRI) in preoperative workup and its influence on planning of radical prostatectomy is still under investigation. The purpose of our study was to evaluate the diagnostic performance of 3-Tesla mpMRI in preoperative staging of PCa in men subjected to endoscopic radical prostatectomy (ERP). We investigated the influence of mpMRI on the extension of resection during ERP.

    Material & Methods

    The study was the retrospective analysis of prospectively collected data of 154 men with PCa in whom mpMRI was performed prior to ERP. Imaging results were compared with pathological reports to investigate diagnostic performance of mpMRI in detecting Extraprostatic Extension (EPE). Initial decision whether to perform NVB sparing surgery was based on EAU guidelines. mpMRI was reevaluated prior ERP to determine feasibility and extent of a NVB preservation.

    Results

    The extent of NVB sparing surgery was changed in 69 (45%) men after reevaluation of mpMRI study. NVB preservation was made in 17 (11%) men, in whom NVB would have been resected, if mpMRI had not been available. The extension of resection was broadened at the expense of narrower NVB preservation in 52 (34%) men, in whom NVB would have been spared, if the decision had been made solely based on guidelines. The change in the extension of resection either to more preserving NVB sparing or more aggressive resection was not correlated with the higher risk of positive surgical margins (PSM). mpMRI had increased diagnostic performance in men with the high-risk cancer (sensitivity 49%, specificity 89%), than in man with low-risk and intermediate-risk cancer (sensitivity 27%, specificity 93%). Despite decreased diagnostic performance of mpMRI in the low-risk and intermediate-risk group, the extension of NVB preservation was narrowed in 17 (63%) and 19 (33%) men, respectively. mpMRI failed to detect or understaged the tumor in nearly half of PSM cases.

    Conclusions

    mpMRI influences decision-making about the extension of resection during ERP irrespective of the prostate cancer risk group. The changes of the extent of resection made basing on the mpMRI result are not related to the increased risk of PSM.

  • Introduction & Objectives

    68Ga PSMA-PET/CT is a novel imaging modality introduced to improve diagnosis and staging of advanced prostate cancer. Due to its naïve nature, robust sensitivity and specificity data outlining 68Ga PSMA-PET positive scans are not available. We aimed to systematically review the current literature and perform a meta-analysis of the reported sensitivity and specificity of 68Ga PSMA-PET.

    Material & Methods

    We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.

    Results

    Five studies reported on the predictive ability of PSMA-PET imaging with respect to histology proven disease, four on a per-patient basis and four on a per-lesion basis. On per-lesion analysis, the summary sensitivity is 80% and specificity is 97%. On per-patient analysis, the summary sensitivity and specificity is 86% though with the low numbers reported in the contributing studies, the confidence intervals are especially wide.

    Conclusions

    To date, pooled data has identified favourable sensitivity and specificity profiles compared to historical values of alternate PET imaging techniques.

  • Introduction & Objectives

    Enzalutamide significantly suppress the growth of prostate cancer, particularly metastatic Castration-Resistant Prostate Cancer (mCRPC), by targeting androgen receptor signaling pathway. However, there are paucity of evidences on the clinical benefits of enzalutamide in Korea. Here, we analyzed the real-world outcomes of enzalutamide treatment in Korean men with mCRPC following chemotherapy.

    Material & Methods

    We retrospectively reviewed the medical records of 110 mCRPC patients who received oral enzalutamide at a dose of 160 mg per day following chemotherapy in three tertiary centers in Korea between 2014 and 2016. Primary endpoint was Overall Survival (OS). Secondary endpoints were time-to first Skeletal-Related Event (SRE), time-to PSA progression and the PSA responsiveness. Kaplan-Meier analysis and log-rank tests were adopted to compare these oncological outcomes according to the various clinicopathological variables. Multivariate Cox regression model was used to identify the predictors for OS.

    Results

    All-cause mortality rate was 18.4% (N=18). The median overall and PSA progression-free were 18.2 months (95% confidence interval [CI], not yet reached) and 9.5 months (95% CI, 6.4 – 12.5), respectively. Notably, patients with poor ECOG scores (≥ 2), visceral metastasis, prior abiraterone treatment, and no concomitant hormonal therapy showed significant worse OS outcomes in Kaplan-Meier analysis (Fig.1). Conversely, there were comparable PSA responses in these subgroups. After adjusting confounding factors among various clinicopathological factors, we finally identified ECOG scores (≥ 2) [hazard ratio (HR), 3.28; 95% CI, 1.11 – 9.68], prior abiraterone treatment (HR, 5.29; 95% CI, 1.68 – 16.67), and concomitant androgen deprivation therapy (HR, 0.19; 95% CI, 0.05 – 0.76) as the independent predictors for OS.

    Conclusions

    In sum, this is the first report for the real-world outcomes of the post-chemotherapeutic enzalutamide in Korean men with mCRPC. Although our study included a small number of patients, it suggests the valuable information for the treatment of mCPRC in a Korean population.

  • Introduction & Objectives

    Urotensin II (UT-II) is a potent vasoconstrictor peptide and its receptor (UTR) was correlated with human cortico-adrenal carcinoma proliferation. In this retrospective study, we have evaluated the correlation between UTR expression and Gleason score of human prostate adenocarcinoma.

    Material & Methods

    We have evaluated the expression of UTR in 143 human prostate tissue samples of patients affected by prostate adenocarcinoma. All patients underwent prostate biopsy prior Radical Prostatectomy between 2009 and 2011. The mean age was 66,2 years (range from 50 to 74 years). Univariate associations between Gleason Score upgrading and clinical and tumour characteristics were assessed using either the chi square test or the Mann-Whitney U test. Multivariable logistic regression models were used to explore the independent role of UTR expression in predicting Gleason upgrading with respect to a set of base prognostic factors including PSA, primary and secondary Gleason score and muscle invasion. The predictive accuracy of the models was evaluated by ROC curve analysis and measured using the Area Under the Curve (AUC). Comparison among the different AUCs was carried out computing the bootstrap sampling distribution of the difference in the two AUCs.

    Results

    55 (38.5%) patients showed a Gleason score upgrading from biopsy on final pathology. The most frequent pattern (n=20, 36.4%) of upgrading was from a biopsy score of 3+4 to a RPP score of 4+3. At univariate analysis, lower primary Gleason, presence of muscle invasion ad higher UTR expression showed a significant association (p<0.001) with Gleason upgrading. Although patients with GS upgrading were characterized by higher PSA values (median [range] PSA: 6.6 [4.8 to 9.5] vs 5.8 [4.4 7.8]), this difference did not reach statistical significance (p=0.215). In a multivariable logistic model including both primary and secondary Gleason score, PSA, muscle invasion and UTR expression levels, patients with an high UTR expression showed a more than ten-fold increase in the odds of upgrading (O.R. 13.77, C.I. 3.1 to 62.5, p<0.001) with respect to patients with low UTR expression. In ROC analysis, this model predicted Gleason Upgrading with an AUC equal to 0.88 (95% C.I. 0.79 to 0.96, p<0.001). With respect to base model not including UTR, the absolute gain in predictive accuracy of the complete model was equal to 9% (p=0.042).

    Conclusions

    These data suggest that the dosage of UTR could be useful to identify a group of patients with a statistically significant high risk of upgrading from biopsy to radical prostatectomy.

  • Introduction & Objectives

    Selective Internal Radiation Therapy (SIRT) is an interventional procedure used for unresectable liver tumours, and has properties that make it potentially useful for primary Renal Cell Carcinoma (RCC) that is unsuitable for nephrectomy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.

    Material & Methods

    Patients (pts) not amenable for or who declined conventional therapy were eligible. A single transfemoral microcatheter administration of Yttrium-90 (Y-90) resin microspheres (SIR-Spheres; Sirtex, Australia) was delivered super-selectively via the renal artery to the tumour at intended radiation doses of 75, 100, 150, 200, 300 Gray and a final cohort with a procedural endpoint of imminent stasis, in a dose-escalation design. Post-SIRT follow-up was 12 months. The primary endpoint was safety and toxicity 30 days post-SIRT. Secondary endpoints included tumour response (RECIST v1.1).

    Results

    The study enrolled 21 pts with RCC (33% left and 67% right kidney), mean age 75.0 years (SD: 9.3; range 48–86) and WHO performance status of 0 (81%) or 1 (19%); gender was 6 (29%) female and 15 (71%) male. Eight pts (38%) had metastatic RCC. Seven pts (33%) had previously undergone total nephrectomy of the contralateral kidney, 1 (5%) received prior chemotherapy and 1 (5%) progressed after cryotherapy to the target organ. Three patients were re-treated within the RESIRT study at a higher Y-90 dose, after at least a 12-month interval from their previous SIRT treatment. Median follow-up was 12.0 months (95% CI 11.9–12.1). Sum of longest diameters for the target lesion was median 45 mm (range 23‒123 mm). The intended Y-90 doses were delivered without any dose-limiting toxicity.  Imminent stasis was reached in 11 (52%) pts. 18 (86%) pts experienced 70 adverse events (AEs) at any time to 12 months, with 8 (38%) pts experiencing 18 SAEs; 4 (19%) pts experienced 5 SAEs within 30 days post-SIRT, all determined as not related to SIRT. Ten (48%) pts had 24 AEs grade ≥3 at any time point to 12 months and all were considered unrelated to SIRT; 9 pts (43%) had 16 AEs that were related to SIRT (all grade 1–2, no SAEs), of which 2 occurred pre SIRT. Treatment-related AEs were fatigue/tiredness/lethargy, pain, hypertension, lack of appetite, nausea, ‘heaviness’, bruised groin andhypomagnesemia. Best overall tumour responses were Partial Response [PR] 1/18 (6%), stable disease [SD] 16/18 (89%) and progressive disease 1/18 (6%), with SD in 2 further patients with on-going follow-up.

    Conclusions

    This pilot study demonstrates good tolerability of SIRT at all dose levels including imminent stasis in treating primary tumours in RCC pts otherwise unsuitable for conventional therapy.

    Session: Oral presentations of the 6 best abstracts

    Location: Saturday, 26 November 2016, 11:15 - 11:55, Auditorium

  • Introduction & Objectives

    This study aims to clarify the clinicopathologic features of long-term survivors after radical cystectomy in muscle invasive bladder cancer patients with lymph nodes metastasis.

    Material & Methods

    We analyzed data on 269 patients at two institutions who underwent radical cystectomy and urinary diversion for bladder cancer between 2006 and 2015 and were observed at least 2 year postoperatively.

    Results

    The incidence of lymph nodes metastasis was 25.2% (68 patients). Urinary diversion was orthotopic bladder substitutions in 16, ileal conduit in 22, ureterocutaneoustomy in 30 patients. Clinicopathologic features associated with above 2-year recurrence free survivors included low grade (p=0.001), no ureteral invasion (p=0.001), adjuvant chemotherapy (p=0.010) (Table 1).

    Conclusions

    This study shows that long-term recurrence-free survival above 2-years after radical cystectomy with pelvic lymphadenectomy can be achieved in patients with favorable tumor characteristics. In addition, ureteral status and adjuvant chemotherapy was reliable predictor of above 2-year recurrence free survivors.

  • Introduction & Objectives

    Circulating Tumor Cells (CTC) are promising biomarkers in advanced prostate cancer. Since they are seeded from metastases they may also serve as liquid biopsies for skeletal metastases that are difficult to sample. The aim of the present study was to evaluate to which extent CTCs reflect the phenotype of skeletal metastases, and thereby their potential to serve as a clinical tool in individualizing treatment of metastatic prostate cancer.

    Material & Methods

    CTC and tissue from skeletal metastases were sampled from 17 patients (5 castration naïve and 12 castration resistant) during surgery for spinal cord compression symptoms. CTCs were sampled prior to removal of metastatic tissue, and isolated with AdnaTest ProstateCancerSelect/Detect (Qiagen). Resulting cDNA was pre-amplified in a multiplex reaction and analysed for expression of 48 genes related to prostate cancer progression and metastasis with qPCR. RNA was extracted from the metastatic tissue with RNeasy Plus Universal Mini kit (Qiagen), and gene expression was assessed in the same way as for CTCs. EpCAM expression level was used as internal control to enable normalization to epithelial content (CTCs or tumor tissue) of the samples. Correlation of detected signals between matched CTC and tissue was calculated with Pearson correlations.

    Results

    In 10 of the 17 patient samples (59%) there was a statistically significant correlation between the gene expression profile of CTCs and the sampled metastatic tissue. In the castration naïve group, 80% of the patients had correlating gene expression in CTC and the metastatic sample, while only 50 % of CRPC patients displayed such correlation. The genes that contributed most to the correlations were AGR2, AKR1C3, FOLH1 (PSMA), CDH1 (E-cadherin) and TACSTD2 (TROP2).

    Conclusions

    This study shows that gene expression patterns in CTC can reflect those of metastases. The high ratio of correlation between CTC and a single metastatic sample in the castration naïve patients may be due to a limited metastatic heterogeneity. Thus, one interpretation of the decreased correlation ratio in CRPC patients is that CTCs reflect the total heterogenic tumor burden rather than the single sample used the present study. Taken together, the results imply that CTC phenotyping is a promising tool for individualized therapy in metastatic prostate cancer.

  • Introduction & Objectives

    Extreme hypofractionated image guided radiotherapy or hypofractionated Stereotactic Body Radiation Therapy (SBRT) in prostate cancer is a novel precise strategy to reduce total treatment time and increase effective doses to the prostatic tumor taking into account prostate cancer and organs at risk radiosenstivity. 1) To evaluate the feasibility and toxicity of two regimens of hypofractionated Stereotactic Body Radiation Therapy (SBRT). 2) To obtain patients self-reported Quality Of Life (QOL) measures in two cohorts of SBRT and to compare with a LDR (Low Dose Rate)-brachytherapy for intermediate risk prostate cancer and HDR (High Dose Rate)- brachytherapy boost after 60Gy of external radiation EBRT for high risk patients.

    Material & Methods

    Two prospective phase I-II studies were approved by our institutional review and ethics board. Inclusion criteria were: Trial1) T1-2N0M0, Gleason Score 6-7, PSA< 20 ng/mL, and IPSS 0-7. Trial 2) T3aN0M0 Gleason score 8 or less (N+risk<25%) and IPSS <13. Hormonal-therapy was prescribed according to risk classification. Image Guided RT with Cone Beam CT was mandatory. Dose SBRT was delivered at a prescribed Planning Target Volume (PTV) 35 Gy in five fractions in 5 alternative days or 9 Gy after 60 Gy 2 Gy per fraction in 30 days, using with RapidArc IMAT, with 6 MV FFF photons. CTCAE v4.0 morbidity scores were used to assess toxicities. Health-related quality of life questionnaire, such as EPIC, was administered centrally by telephone interview before treatment and during follow-up (at 3, 6 and 12 months). Comparison of QLQ values by confidence intervals was done between Trial 1 patients and a cohort of 280 LDR-brachytherapy patients and external radiation combined plus HDR-brachytherapy 9 Gy boost in 88 patients vs Trial 2 patients. This work was supported by a grant from the Fundación Mutua-Madrileña (AP87652011).

    Results

    Thirty-one patients have been recruited. Mean age was 70.6 years. Nineteen patients were included in trial 1 and 12 in trial 2. According to D'Amico risk classification for trial 1), 3/19 patients were low-risk and 16/19 were intermediate risk, for trial 2) 12 patients were high risk. All patients completed the treatment as programmed with good tolerance. No toxicity greater than grade 2 was observed. Acute GU and rectal toxicities were seen in 20/31 (64.5%) and 17/31 (54.8%) patients respectively. Both GU and rectal late toxicities G 2 were: 2/31 (6.4%) and 1/31 (3.2%). EPIC urinary values were significantly better at 3 and 6 moths for SBRT (5x7) vs LDR-brachytherapy and EPIC hormonal was higher at 3, 6 and 12 months in LDR-brachytherapy group, whereas in 9 Gy boost patients EPIC hormonal was lower at baseline and 3 months in SBRT group. Values on both bowel and sexual did not showed differences.

    Conclusions

    Early findings indicate that both SBRT regimes with IMAT and FFF beams for low-intermediate-risk prostate cancer and high risk are feasible and well tolerated in selected patients. Although EPIC hormonal QLQ measures are worse than brachytherapy cohorts, EPIC values related to radiation treatment are not different. Long-term follow-up is needed for assessment of late toxicity and outcomes.

  • Introduction & Objectives

    Penile cancer (NP) is a rare neoplasm, accounting for <1% of the tumors in man. The reduced incidence of this condition results in a limited number of randomized trials and low evidence for the best therapeutic approach. We describe a 15-year single center experience in the management of patients with PC.

    Material & Methods

    Retrospective analysis of 55 patients with PC, between 2000 and 2014. The association between categorical variables was evaluated by chi-square test or Fisher's exact test. The survival analysis was performed using the Kaplan-Meier method and log-rank test to compare groups.

    Results

    55 patients with a mean age of 61.1 ±12.2 years [34.0 to 84.0]. 80.9% of the patients presented risk factors for PC (previous STDs 44.7%, phimosis 37,8% and balanitis 28.9%). Most patients presented a single (86.7%), vegetating lesion (56.3%) with an average duration of 12.9 ±15,9 months [2-60] and an average diameter of 31.7 ± 20,9mm [10.0 to 100.0]. 37,5% of the lesions were located in the glans (37.5%), followed by the sulcus (25%) and penile shaft (20.8%). Palpable lymph nodes were reported in 43.2% of patients, predominantly bilateral (50.0%) and mobile (62.5%). Squamous cell carcinoma was diagnosed in 98.0% of the cases, mostly well and moderately differentiated (45.2 and 40.5%, respectively), with lymphovascular invasion in 14.6%. The main surgical intervention was partial penectomy (69,1%), followed by wide excision of the lesion (16.4%) and glansectomy (5.5%). 8.6% of patients had previously undergone topical treatment. In terms of pathological staging, 10.7% had noninvasive disease (CIS / pTa), 27.6% pT1, 31.9% pT2, 27,7% pT3 and 2.1% pT4. Negative lymph node staging (cN0 and pN0) in 74.4% of the patients, N2 in 17.0% and N3 in 8.5%. Radical inguinal lymphadenectomy was performed in 30.6% of patients, with a mean number of nodes removed of 15.3 ±5.6 [1-25]. Pelvic lymphadenectomy was performed in 12.2% of the patients. 18.0% of patients had recurrence after surgical treatment, with a time interval between treatment-recurrence of 5.5 ± 3,9meses [1.0 to 12.0]. The correlation of several clinical and pathological variables with the risk of recurrence, lymph node involvement (N +) or metastatic disease (M +), showed a clinically significant association between greater diameter of the lesion and higher risk of recurrence (p = 0.027), and between palpable lymph nodes and greater risk of inguinal N+ (p = 0.004) and M+ (p = 0.026). Differential survival analysis, according to pT stage, lymph node involvement (N) or metastatic (M0/M +) confirmed lower survival rate of the most advanced stages. We register an overall mortality rate of 29.8%, for a mean follow-up of 41.2 months ± 32.8 [1.0 to 123.0].

    Conclusions

    The described cohort shows aggressive characteristics, with a high percentage of lesions in penile shaft (20.8%), ≥pT2 staging (61.7%), nodal involvement (25.5%) and metastatic disease (12.5%). This factor was reflected in a higher rate of radical surgical approaches and inguinal lymphadenectomy. In the series presented the diameter of the lesion was correlated with higher risk of recurrence and the presence of palpable lymph nodes with increased risk of N+ and M+. Survival curves reflect more aggressive disease at advanced stages.

  • Introduction & Objectives

    Dose to the bladder trigone is associated with increased Genito-Urinary (GU) toxicity in prostate radiotherapy studies. Its role in Muscle Invasive Bladder Cancer (MIBC) is unknown. The relationship between GU toxicity grade (G) and dose to trigone was determined in patients who received high-dose focal tumour boost (≤70Gy) within a prospective phase 1 image-guided adaptive radiotherapy dose escalation study (NCT01124682).

    Material & Methods

    Patients with localised MIBC were treated with a plan of day approach, treating whole bladder to 52Gy and tumour to 70Gy in 32 fractions. Following completion of treatment, bladder trigone surrogate structure was retrospectively contoured on the planning CT as a triangle-shaped region at the posterior wall that encompassed the transition of the urethra into the bladder caudally and the ureteric orifices cranially. Cumulative dose to trigone was determined by summation of selected plans used for treatment delivery. ROC analysis was used to identify significant dose constraints (AUC > 0.6 and p < 0.05) predictive of acute peak and emergent peak ≥G2 toxicity as measured using CTCAE v3.0. AUC cut point values were determined by Younden index. Peak toxicity was the highest score occurring either at baseline, weekly during radiotherapy or at 4, 8 and 12 weeks following radiotherapy. Emergent peak score was the difference between peak score (up to 12 weeks) during follow-up and baseline. The probability of peak and emergent ≥G2 acute events was calculated using logistic regression. Constraints predicting 20%, 30%, 40% and 50% probability of acute GU toxicity was determined.

    Results

    20 patients (14 males; 6 females) recruited to the study protocol between June 2012 and May 2014 were evaluated. All patients had stage T2-T3N0M0 transitional cell carcinoma of the bladder. Median age was 73 years (range 50-90). Baseline G0, G1 and ≥G2 toxicity was 45%, 45%, and 10%; peak G0, G1 and ≥G2 toxicity was 0%, 30% and 70%; emergent G0, G1 and ≥G2 toxicity was 20%, 55% and 25%. No G4 toxicity was seen at any time point. Significant association of emergent ≥G2 toxicity was identified at trigone V60 >5.6cm3 (AUC 0.81, 95% CI 0.60-1.0; p=0.040), V65>5.6cm3 (AUC 0.89, 95% CI 0.69-1.0; p=0.010), V70>3.6cm3  (AUC 0.87, 95% CI 0.65-1.0; p=0.016) and V70>61.0%.  (AUC 0.81, 95% CI 0.57-1.0; p=0.040). No significant AUC was associated with peak ≥G2 toxicity. Table 1. Predicted probability of emergent ≥G2 acute GU toxicity.

    Trigone Threshold constraint for % predicted probability
    Relative volume (%) Absolute volume (cm3)
     20% 30% 40% 50% 20% 30% 40% 50%
    V50 99.3 99.4 99.5 99.5 7.9 7.9 7.9 7.9
    V55 79.5 80.5 81.0 85.0 6.0 6.1 6.3 6.4
    V60 60.0 62.0 65.0 68.5 4.5 4.7 4.9 5.2
    V65 50.0 54.5 58.0 61.5 3.7 4.0 4.3 4.5
    V70 28.5 32.0 36.0 40.0 2.1 2.3 2.6 2.9

    Conclusions

    Bladder trigone dosimetric predictors of acute GU toxicity have been characterised and novel constraints are proposed to reduce GU events in future bladder radiotherapy dose escalation protocols following validation. Further work is also neeeded to determine impact of trigone dose on long-term GU toxcity in bladder radiotherapy.

  • Introduction & Objectives

    Upper urinary tract urothelial carcinoma (UUT-UC) is relatively rare, account for 5 to 10% of all urothelial carcinomas. The biologic behavior and clinical outcomes of patients with UUT-UC are dependent on the pathological (pT) stage, grade and lymphovascular invasion (LVI) in some studies. However, urothelial carcinomas in the upper urinary tract as well as bladder can exhibit a wide variation in biological behaviours and clinical outcomes. Surviving is a member of the inhibitor of apoptosis protein family that is over-expressed in many malignancies including urothelial carcinomas but rarely detected in normal differentiated adult tissues. To our knowledge, only several studies have dealt with surviving expression in UUT-UC. We retrospectively studied the expression of surviving in UUT-UC using immunohistochemical methods and determined whether its expression is associated with prognosis.

    Material & Methods

    Forty-six UUT-UC specimens obtained at nephroureterectomy were examined for expression of surviving with a mouse monoclonal antibody (Clone 12C4, Dako, Glostrup, Denmark) against surviving protein. The immunohistochemical results were analyzed by evaluating the percentage of tumour cells with positive staining on the total neoplastic cell count from 10 representative fields at 400-magnification. The cutoff was estimated as 20% of antibody-stained cells, at which point the sample was considered immune-positive. Cancer-specific survival (CSS) was performed according to the Kaplan-Meier method, and the Cox proportional hazard model was used to compare the relative influence of different prognostic factors. The median-flow-up was 41 months (range: 3-157 months).

    Results

    Of 46 patients 21 (46%) had surviving positive urothelial carcinomas. The survivingimmunoreactivity was significantly related to high pT stage (p=0.0454) and high grade (p=0.0085). The 10-year CSS outcomes for the surviving immune-positive group and negative group were 28% and 78%, respectively (p=0.0131). In a univariate analysis, high pT stage (p=0.0071, pT3 or more n=24 vs pT2 or less n=22), high grade (p=0.0109, high n=25 vs low n=21), positive LVI (p=0.0118, positive n=22 vs negative n=24) and surviving expression (p=0.0210, positive n=21 vs negative n=25) were associated with unfavourable CSS. However, multivariate analysis including these significant variables by univariate analysis showed that the parameters were not significantly related to the CSS.

    Conclusions

    Although in multivariate analysis no independent influence of survivin on patient prognosis was found, surviving expression may be a potential predictive marker of prognosis in UUT-UC. However, prospective study including a large number of cases is needed to confirm the prognostic utility of surviving.

  • Introduction & Objectives

    One of the surgical techniques utilized to treat prostate cancer is Radical Perineal Prostatectomy (RPP). This technique offers good anatomic visualization and allows for precise dissection of the prostate away from the Neurovascular Bundles (NVBs). Our objective was to evaluate urinary continence following RPP.

    Material & Methods

    66 RPPs were conducted between 2013 and 2015. The mean age of the patients was 62 (53-71) years. The mean preoperative PSA level was 6.9 (4.2-9.8) ng/ml. The mean prostate volume was 42 (21-72) cm3. All patients had the Gleason score of ≤ 7. 47 patients (71%) had clinical stage T1, and 19 patients (29%) had T2. The surgeries were performed using Young’s suprasphincteric approach modified by Belt. All patients were divided into 2 groups. In group 1, the patients (n=45, 68%) underwent nerve-sparing RPP. In group 2, the patients (n=21, 32%) underwent non-nerve-sparing RPP. This study evaluated urinary continence in patients with and without the preservation of the NVBs.

    Results

    In group 1, catheters were removed on postoperative day 6 or 7. In group 2, they were removed on postoperative day 6, 7, or 8. Following catheter removal, 33 patients in group 1 (73%) regained full urinary continence, and 12 patients (27%) had Grade 1 incontinence, while in group 2, full urinary continence was observed in 10 patients (48%), and Grade 1 incontinence in 11 patients (52%). No cases of Grade 2 incontinence or total urinary retention were noted. At 6 months of follow-up, in groups 1 and 2 full urinary continence was observed in 39 patients (87%) and 15 patients (72%), respectively. At 12 months of follow-up, in groups 1 and 2 full urinary continence was observed in 44 patients (98%) and 18 patients (86%), respectively.

    Conclusions

    Perineal access provides better visualization of the operative field, which allows for precise separation of the NVB and precise vesicourethral anastomosis. The advantages of nerve-sparing RPP are shorter catheterization time and faster return of full urinary continence. However, at 1 year of follow-up, no significant differences in urinary continence between the two groups were observed.

  • Introduction & Objectives

    With its excellent resolution of adipose tissue, CT presents precise quantitative assessment of visceral fat accumulation. We assessed the impact of visceral fat accumulation on progression free and overall survival in patients treated with 
    systemic therapy for metastatic renal cell carcinoma.

    Material & Methods

    This retrospective cohort study included 114 patients treated with systemic therapy for metastatic renal cell 
    carcinoma between 2007 and 2015 at Keio university hospital in Japan. The visceral fat area was measured at 
    the level of umbilicus using CT. The tomographic attenuation of the adipose tissue was defined to be between 
    −50 and −150 HU. A visceral fat area ≥100cm2 was used as the definition of visceral fat accumulation. 
    Progression free and overall survival was compared according to visceral fat accumulation.

    Results

    The mean visceral fat area was 107.4 ± 62.8 cm2. In the whole cohort, the median progression free survival in first 
    line treatment was 12.0 month. The median overall survival was 42.5 month. According to Memorial Sloan-Kettering Cancer Center classification, 31 patients were favorable risk, 61 were intermediate risk, and 22 were 
    poor risk; median overall survival for these groups were 76.9, 40.8, and 23.7 months, respectively (P<0.0001). 
    Visceral fat accumulation correlated with improved progression free (P=0.0070) and overall survival (P=0.0001). 
    On multivariate analysis, visceral fat accumulation (P=0.0290) and Memorial Sloan-Kettering Cancer Center classification (P=0.0085) were independent indices to predict progression free survival 
    in first line treatment. In addition, visceral fat accumulation (P=0.0153) and Memorial Sloan-Kettering Cancer Center classification (P=0.0004) independently predicted overall survival.

    Conclusions

    The precision of CT imaging for measuring visceral fat area provides useful clinical venue to predict prognosis 
    for metastatic renal cell carcinoma. Visceral fat accumulation may be a useful and independent indicator for a 
    better prognosis in patients treated with systemic therapy for metastatic renal cell carcinoma.

  • Introduction & Objectives

    Amyloidosis is a rare disorder that results from the extracellular deposition of misfolded proteins in fibrils responsible for tissue compression, damage and functional impair. There are 4 main types of amyloid proteins: AL – light chain - plasma cell proliferation and the systemic amyloid, AA type – increased in chronic inflammatory states, Aß amyloid- brain lesions of Alzheimer patients, ATTR - familial amyloid polyneuropathies. Amyloidosis may be localized or systemic. Localized amyloid of the lower urinary tract is uncommon and amyloid of urethra is exceedingly rare. Since 1909 50 cases of urethral amyloid were reported.

    Material & Methods

    A clinical case report.

    Results

    We present the case of a 29 year old male with 3-4 months duration of lower urinary tract symptoms including dysuria, macroscopic hematuria, hematospermia and urethral discharge. He presented with repeatedly negative urine cultures, urine cytology PAPI, and a complete STD screen negative. On clinical examination an endured elastic mass with approximately 4cm was palpable at the bulbar urethra. Physical examination was otherwise unremarkable. No post-micturition residual urine was detected on ultrasound. MRI showed hypertrophy of bulbar urethral wall with low signal intensity on T1-weighted, T2-weighted and an enhancement after application of Gadolinium contrast. A transurethral biopsy was obtained from a group of white solid with superficial papillary character masses 8cm proximal to the external urethral orifice and sent to pathological examination and an optical urethrotomy performed. The examined tissue stained positive with Congo red and birefringence detected under polarized light – amyloid. Immunohistochemistry excluded the presence of kappa and lambda chains, excluding AL type. The patient was seen 1 month after the surgery, there was a regression of the LUT symptoms by 40% and the patient referred to Internal Medicine for further investigations.

    Conclusions

    Amyloid in the urethra is a rare diagnosis, it mimics primary urethral tumor, non-specific urethritis or stricture and its management is mostly conservative. A multidisciplinary approach is recommended.

  • Introduction & Objectives

    EPI-506 is a first-in-class, highly specific small molecule inhibitor of the Androgen Receptor (AR) N-Terminal Domain (NTD). Preclinical studies have shown significant activity against both full length AR as well as resistance-related AR species such as AR splice variants, including AR-V7 (associated with resistance to abiraterone and enzalutamide). EPI-506 is expected to be effective in mCRPC driven by canonical and aberrant AR signaling by inhibiting the transcriptional activity of the NTD. Initial clinical development of EPI-506 will target mCRPC with progression after prior enzalutamide and abiraterone. A phase 1/2 trial of EPI-506 is ongoing and represents the first investigation of an AR NTD inhibitor.

    Material & Methods

    This is an ongoing open-label, single-arm, phase 1/2 study evaluating the benefit of EPI-506 at once-daily dosing. The phase 1 portion will establish the safety, Pharmacokinetics (PK) and Maximum Tolerated Dose (MTD) of EPI-506. PSA response at week 12, defined as a ≥ 50% PSA decrease from baseline, and time to PSA progression will also be evaluated. The phase 2 portion of the study will evaluate activity in 3 patient populations: post-enzalutamide mCRPC, post-abiraterone mCRPC, and post -abiraterone and -enzalutamide mCRPC. Inclusion criteria include mCRPC with progression after one or more lines of hormonal therapy, and progression on enzalutamide or abiraterone. Exclusion criteria include hematologic, hepatic or renal insufficiency. Plasma concentrations were measured over 48 hours to assess PK in fasted and fed states. Exploratory endpoints include evaluation of AR splice variants and AR mutations from CTC-based and cfDNA-based methodologies.

    Results

    Data to address the phase 1 primary endpoint of safety and tolerability, as well as secondary endpoints, including PK and PSA response, are currently being collected in this ongoing trial (trial in progress).

    Conclusions

    This clinical study will be the first to evaluate the novel AR NTD inhibitor EPI-506 in men with enzalutamide- and/or abiraterone-resistant mCRPC, and is the first agent with the potential to inhibit both canonical and variant-mediated AR signaling. Clinical trial information: NCT02606123

  • Introduction & Objectives

    The optimal management of pelvic or retroperitoneal nodal Prostate Cancer (PCa) recurrences after primary treatment remains largely undefined. These patients are usually treated in the same way as those with distant metastases by means of Androgen Deprivation Therapy (ADT). We want to report the outcome of Stereotactic Body Radiotherapy (SBRT) for oligorecurrent nodal PCa.

    Material & Methods

    This was a retrospective multicentre analysis of patients diagnosed with 3 metachronous nodal recurrences treated with SBRT. SBRT was defined as a radiotherapy dose of at least 5 Gy per fraction to a Biological Effective Dose (BED) of at least 80 Gy to all metastatic sites. The study was approved by the central ethics committee (EC2014/ 0199). Inclusion criteria were as follows: histologically proven diagnosis of PCa, biochemical relapse of PCa after radical local prostate treatment and the detection of up to three N1 or M1a lesions. Patients were excluded in the case of M1b or M1c lesions, serum testosterone levels 12 months with SBRT, previous pelvic radiotherapy, biochemical relapse while on active treatment with a systmemic agent for PCa.  
    The primary endpoint was Distant Progression-Free Survival (DPFS), defined as the time interval between the first day of SBRT and appearance of new metastatic lesions, outside the high-dose region. Secondary endpoints were local control, time to start of palliative ADT and toxicity scored using the Common Terminology Criteria for Adverse Events v4.0.

    Results

    Overall, 171 metastases were detected (84% with choline PET-CT) and treated with SBRT in 134 patients. The median follow-up from SBRT was 29 mo (IQR: 13-47). Adjuvant ADT was given in 33% of patients for a median duration of 6 mo (IQR: 1-8 mo). The median DPFS was 21 mo (95% CI: 18-24 mo) with 80% of patients having ≤3 metastases at time of progression. The 3-year local progression rate was 41% for patients treated with a BED 100Gy (p<0.001). The median time from first SBRT to the start of palliative ADT was 25 mo (95% CI: 18 – 32). Late grade I and II toxicity was observed in 10% (N=13) and 4% of patients (N=6). No grade 3 toxicity was observed.

    Conclusions

    SBRT for oligometastatic PCa nodal recurrence is safe. The majority of subsequent relapses remain nodal and oligometastatic.

  • Introduction & Objectives

    Radical Prostatectomy (RP) is one major treatment option in prostate cancer. Depending on risk factors, 50-80% of the patients experienced biochemical recurrence (data from the ARO 96-02 trial). After recurrence, Salvage Radiotherapy (SRT) offers a second chance of cure: Around 60% of the patients can re-achieve an undetectable PSA after SRT and approximately 80% of these men are free from recurrence, 5 years later on. European guidelines (EAU) recommend SRT at a PSA <0.5 ng/ml. We analyse the efficacy of SRT given according to this recommendation and investigate the predictive power of the post-SRT PSA nadir.

    Material & Methods

    Between 1998 and 2013, 301 patients of two university hospitals received SRT for post-RP (N0) recurrent prostate cancer at a PSA <0.5 ng/ml. All had 3D-conformal RT (median 66.6 Gy) including 40 cases with IMRT. The median follow-up in this retrospective analysis was 5.9 years (max 13.3). Progression as defined by Stephenson et al. (JCO 2007) and overall survival were the endpoints.

    Results

    After RP, 260 patients achieved a PSA in the undetectable range (<0.1 ng/ml), 41 had a persistent or rising PSA. First recurrence was stated in median 0.9 years after RP (IQR 0.3-1.9). The median time from RP to SRT was 1.6 years (IQR 0.7-2.3). After SRT, 252 patients re-achieved an undetectable PSA, 49 retained higher values. There were 92 second recurrences and 17 patients died. In univariate analysis, the following parameters correlated unfavorably with post-SRT progression: pre-RP PSA ≥10 ng/ml, pT3-4, Gleason score (GLS) 7-10 or 8-10, negative surgical margins (R0), post-RP PSA ≥0.1 ng/ml, pre-SRT PSA ≥0.2 ng/ml and post-SRT PSA nadir ≥0.1 ng/ml. There was no subgroup that did not benefit from SRT at PSA <0.2 ng/ml. In backward excluding Cox regression analysis, pT3-4 (Hazard ration HR=2.29), GLS 7-10 (HR=2.52), negative margins (HR=1.68) and a pre-SRT PSA ≥0.2 ng/ml (HR=1.71) were significant risk factors. If the post-SRT PSA was added to that model, it dominated the outcome (HR=9.00). Of the patients with a pre-SRT PSA <0.2 ng/ml, only 9% failed re-achieving an undetectable PSA; with a higher pre-SRT PSA, 24% did so. This difference also had an impact on overall survival which was 98% vs. 91% after 5.9 years (Logrank p=0.004) favoring men with a post-SRT PSA <0.1 ng/ml.

    Conclusions

    SRT at a PSA <0.2 ng/ml correlates significantly with achieving a post-SRT undetectable PSA (<0.1 ng/ml) and subsequently with improved freedom from progression. In patients who had SRT at a PSA <0.5 ng/ml, an undetectable post-SRT PSA-nadir was the strongest predictor of freedom from progression and overall survival. The nadir may help to identify patients, who can benefit from additional systemic treatment. The recommended PSA cut-off for SRT should be reconsidered.

  • Introduction & Objectives

    71-85% Castrate Resistant Prostate Cancer (CRPC) patients revealed Neuroendocrine Differentiation (NED) of tumor tissue. The most valuable serum NED marker is Chromogranin A (CgA), the sensitivity of which reaches 60-70%. According to our data 34% of CRPC patients revealed increase in CgA serum level (more than 3 nmol/l), which is probably caused by NED development on the background of a long-term hormonal treatment. Based on these data, the evaluation study of CgA serum prognostic role in pathogenetically based somatostatin analogues (octreotide depo) CRPC patients treatment looks promising.

    Material & Methods

    The study includes 49 men with CRPC (T3-4N0-1M1), who were divided in 2 groups. Group I included 21 patients with elevated level of CgA › 3 nmol/l, Group II – 28 patients with normal CgA level. Combination therapy included octreotide depo 20-30 mg once every 28 days with dexamethasone in a dose of 4 mg per day for one month. Further on dexamethasone was administered in a dose of 2 mg per day for 2 weeks, after which the dose was reduced to 1 mg per day (maintenance dose). All patients were also prescribed with GnRH analogues, except those after surgical castration. In course of treatment all patients were CgA and PSA tested.

    Results

    Significant difference was revealed between the groups with number of patients in PSA decrease > 25% and > 50%. In Group I PSA progression was detected in 6 (29%) patients, and median time to PSA progression made 6 months. In Group II PSA progression was detected in 18 patients (64%), median time to PSA progression was 3.5 months (figure below). The difference between groups is statistically significant (p<0.05).

    Groups Number of patients Initial CgA level(nmol/l) in groups PSA Median time to PSA progression (TTPP) in groups (months)
    ↓PSA ≥25% ↓PSA≥50% PSA↑
    I (CgA↑) 21 5,9 15(71%) 11(52%) 6(29%) 6,0 (p<0,05)
    II
    (CgA N)
    28 1,6 10(36%) 4(14%) 18(64%) 3,5

    Conclusions

    CgA level is a valuable factor for effectiveness prognosis of somatostatin analogues  treatment in CRPC patients. The elevating initial CgA level showed decrease PSA >25% in 71% of octreotide depo treatments. This work was initiated and carried out by its authors without any sponsorship.

  • Introduction & Objectives

    Non-Muscle Invasive Bladder Cancer (NMIBC) accounts for 75% of all bladder cancer cases and it’s treated by Transurethral Resection of Bladder Tumor (TUR-BT) and intravesical treatments. However, the exact surveillance protocol and treatment regime vary among countries. Major guidelines support the role of repeat resection within 4–6 weeks after initial resection in cases of incomplete resection and in cases of high grade pTa and pT1 bladder tumor where detrusor muscle was not present. The tumor is often understaged by primary resection. The likelihood that muscle invasive disease is found by second resection of initially T1 tumour varies between 4% and 25%, and it rises to 45% if there is no muscle included in the initial resection. It has been seen that a repeat TUR-BT(Re-TUR) can increase recurrence-free survival, improve outcomes after BCG treatment, and provide prognostic information. Purpose: In this retrospective study, it is aimed to indicate the necessity of repeat transuretral resection of bladder in non-muscle invasive bladder cancer.

    Material & Methods

    51 patients with non-muscle invasive bladder tumor (Ta-T1) undergoing TUR-BT and second TUR-BT 4-6 weeks after the initial resection were included in the study. Re-TUR was performed to the scar of the first resection and other suspicious lesions in the bladder.

    Results

    From January 2012 to June 2016, 51 patients were included in the study. Operations were performed by 5 urologists who work in the same clinic. Mean age was 65. At the first TUR-BT, 15 (29%) patients had multiple lesions and 36 (71%) had a solitary tumor. 28 (54%) of initial TUR-B’s were radiologically bigger than 3 cm whereas 23 (46%) of them were smaller than 3 cm. Re-TUR revealed histological residual tumors in 22 (43%) patients. Residual tumor ratio was 46% in patients with a tumor bigger than 3 cm in initial TUR-BT while the ratio was 39% in patients with a smaller tumor. While T1 bladder cancer was found in 34 of patients who underwent initial TUR-BT, residual tumor was detected in 17 (50%) of them in Re-TUR. This ratio was 29% in patients who had Ta bladder cancer in initial TUR and underwent Re-TUR. T2 bladder cancer was found in Re-TUR operations of 4 (11%) of 24 patients who were diagnosed with T1 bladder ca in initial TUR-BT and this indicates the importance of Re-TUR.

    Conclusions

    Residual tumor may remain after initial TUR-BT performed to Ta High grade and T1 bladder cancer patients and this indicates the need for  Re-TUR. As it is demonstrated in our study of 51 patients  the need of Re-TUR for patients with T1 grade in initial TUR-BT is more significant. Muscle invasive bladder cancer after Re-TUR is seen in 11% of patients who have T1 bladder cancer in initial TUR-BT. Downstaging is seen in initial TUR-BT and this shows the significance of Re-TUR.

  • Introduction & Objectives

    Although several studies have reported prognostic factors in men treated with Abiraterone Acetate (AA) for Castration-Resistant Prostate Cancer (CRPC), there have not been established a prognostic model for Japanese patients. In this study, we analyzed prognostic factors in Japanese men treated with AA for CPRC.

    Material & Methods

    A total of 122 patients treated with AA for CRPC in 14 institutions were analyzed retrospectively. We examined the correlation between Overall Survival (OS) after AA and clinicopathological characteristics including initial PSA levels, Gleason scores, patients’ age, PSA levels at AA induction, previous treatment with docetaxel, and the time to CRPC from initial treatment.

    Results

    Median initial PSA level was 172.2 ng/mL and 82 patients (67.2 %) had Gleason score ≥8. Median age and PSA level at AA induction was 76.8 years and 26.8 ng/mL. Previous treatment with docetaxel was performed in 56 patients (45.9 %). Median time to CRPC was 12.5 months. At the median follow-up of 6.0 months, PSA reduction ≥50 % were observed in 34 patients (30.4 %), and median OS was 28.1 months. In multivariate analysis, two significant risk factors for OS were identified; PSA levels at AA induction (>26.8 ng/mL vs ≤26.8; HR 4.874, 95 % CI 1.649-14.404, p=0.004) and previous treatment with docetaxel (yes vs no; HR 3.586, 95 % CI 1.335-9.633, p=0.011).

    Conclusions

    PSA levels at AA induction and previous treatment with docetaxel could be the significant prognostic factors in Japanese men treated with AA for CRPC. These findings might support the clinical management of men with CRPC.

  • Introduction & Objectives

    Neutrophil to lymphocyte ratio (NLR) is a preoperative marker of systemic inflammation that has been related to worse oncological outcome and survival in a variety of malignancies. The aim of our study was to evaluate the association between preoperative NLR and various clinical and pathological characteristic of patients undergoing radical cystectomy (RC) due to bladder cancer and its utility as a prognostic preoperative biomarker.

    Material & Methods

    We performed a retrospective review of 164 CR performed at our center between September 2009 and January 2016. Then, we obtained the absolute values ​​of neutrophils and lymphocytes from the preoperative blood sample that helped us calculate the NLR for each patient. Patients were then divided into two groups according to the results of pathology analysis after the surgery (AP) cataloging them in good prognosis AP and poor prognosis AP (T3-4 or N>1). We checked if there were differences based in NLR regarding this division (U- Mann Whitney) and determined a cut off point for the NLR (ROC curve). Bivariate analysis was performed to study the association between NLR and other clinical- pathological features (BCG prior preoperative hemoglobin, hydronephrosis, etc.) with worse oncological results and cancer specific survival (Chi square and T- student). Finally, we carried out a comparative analysis of survival based in NLR groups (Kaplan Meier).

    Results

    We analyzed 164 patients (144 men and 20 women) with a mean age of 68'72 years (33- 85) and a postoperative follow up of 25'53 months (0- 84). The stablished cutoff value of NLR of 2’7 showed an area under the ROC curve of 61% (p=0'001). A NLR > 2.7 was associated with poor prognosis AP (p=0'001) and a trend towards increased cancer specific mortality (p=0'19- 0'98). Besides, the survival distributions according NLR showed statistically significant differences (p=0'024).

    Conclusions

    The value of preoperative NLR can be an economic and readily available prognostic marker, that along with other clinical variables, may help us stratify patients into risk groups and thus facilitate preoperative decisions such as the need of administrating neoadjuvant chemotherapy. However, prospective studies that include a greater number of patients are needed to increase the statistical power of our results.

  • Introduction & Objectives

    Nonagenarian population in the UK has doubled in the last 20 years. Old age is the greatest risk factor for developing bladder cancer. These patients usually face barriers with accessing and receiving healthcare; they are also known to get less aggressive treatment because of co-morbidities. We conducted a study of bladder cancer, recurrences and mortality rates in patients 90+ years.

    Material & Methods

    Patients with bladder cancers 90+ years between 2003 and 2015 in our hospital in North Wales were looked at retrospectively.

    Results

    Out of 652 patients with bladder cancer, 22 were nonagenarians at diagnosis, 21 Transitional Cell Carcinomas (TCC), and 1 neuroendocrine tumour (Females 59%; Mean Age 92.2 years, range 90-99). Tumour grades were G1 (N = 6, 27%), G2 (N = 5, 23%), and G3 (N = 11, 50%). Five out of seven patients with tumour recurrences died. Out of 15 patients without recurrences, 10 died (67%). There was no significant effect of recurrence on mortality (p = 0.82). The tumour staging of patients at presentation: pTA (N = 10, 46%), pT1 (N = 6, 27%) and pT2 (N = 6, 27%). Mortality across stages was pTA (N = 6, 60%), pT1 (N = 4, 67%) and pT2 (N = 5, 83%), this difference not being statistically significant (p = 0.62).
                

    Conclusions

    In our study, bladder tumours in nonagenarians are predominantly high grade (G3). Management should be dictated by associated co-morbidities and performance status not by age alone.

  • Introduction & Objectives

    In patients with prior negative prostate biopsies and a persisting suspicion on Prostate Cancer (PCa) clinical guidelines advise to perform MRI diagnostics, followed by Targeted Biopsy (TB) if tumour suspicious lesions are visible. Additionally Systematic Biopsies (SB) can be performed. In this interim analysis of the FUTURE trial the detection rates of (significant) PCa using TB are compared with the detection rates using SB.

    Material & Methods

    The FUTURE trial has been including patients with prior negative prostate biopsies and a suspicion on prostate cancer (PSA≥4 and/or abnormal DRE) since 2014. Patients are initially subjected to MRI diagnostics. Images are centrally evaluated by an expert radiologist (J.O.B.) using PIRADS v2. If imaging demonstrates tumour suspicious lesion (PIRADS≥3) patients are randomised 1:1:1 for one of three techniques of TB (MRI-TRUS fusion, cognitive TRUS, and in-bore MRI). In both the MRI-TRUS fusion and the cognitive TRUS groups, SB was performed in addition to TB. TB was performed initially, followed by SB using a standardised template irrespective of the location of MRI lesions. Overall PCa and significant PCa (Gleason≥7) detection rates were compared using McNemar test.

    Results

    Of the 362 patients subjected to MR imaging, 130 (35.9%) had PIRADS≥3 lesion on imaging. Of these patients 84 have undergone both TB and SB. See table 1 for baseline characteristics. Using TB PCa was detected in 52.4% (n=44) and significant PCa in 34.5% (n=29). Using SB PCa was detected in 33.3% (n=28) and significant PCa in 17.9% (n=15). See table 2 for a cross tabulation of biopsy outcomes. TB detected significantly more PCa (p=0.003) as well as significantly more significant PCa (p=0.001) than SB. In patients in whom SB did not detect PCa, TB detected PCa in 25% (n=21), and significant PCa in 14% (n=12). Alternatively in patients in whom TB did not detect PCa, SB detected PCa in 6% (n=5) and significant PCa in 1% (n=1)  
    Table 1

      All (n=84)
    Age (mean) 66.0
    PSA (mean) 10.8
    Volume TRUS (mean) 46.0 mL
    Clinical stage DRE
    ·                    cT0
    ·                    cT2a/b
    ·                    cT2c
    ·                    cT3a
     
    81.0%
    16.7%
    2.4%
    -
    Number of prior negative biopsies 1.6
    PIRADS v2
    ·                    1
    ·                    2
    ·                    3
    ·                    4
    ·                    5
     
    -
    -
    31.0%
    34.5%
    34.5%
    Number of TB cores (mean) 3.9
    Number of SB cores (mean) 10.0

     
    Table 2

    N=84   Systematic biopsy Total
        No cancer Gleason=6 Gleason≥7  
    Targeted biopsy No cancer 42% 5% 1% 40
    Gleason=6 11% 7% 0% 15
    Gleason≥7 14% 4% 17% 29
    Total   56 13 15 84

    Conclusions

    TB has significantly increased detection rates of all PCa, and significant PCa compared to SB in subjects with prior negative prostate biopsies and a persisting suspicion on PCa.

    Session: Oral presentations of the 6 best abstracts

    Location: Saturday, 26 November 2016, 11:15 - 11:55, Auditorium

  • Introduction & Objectives

    Circulating tumour cells serve as useful biomarkers with which to identify disease status associated with survival, metastasis and drug sensitivity. Here, we established a novel application for detecting PSA/PSMA-positive prostate cancer cells circulating in peripheral blood employing an adenovirus called Ad5/35E1aPSESE4.

    Material & Methods

    Ad5/35E1aPSESE4 utilized PSES, a chimeric enhancer derived from PSA/PSMA promoters that is highly active with and without androgen.

    Results

    A fluorescence signal mediated by GFP expression upon Ad5/35E1aPSESE4 infection was selectively amplified in PSA/PSMA-positive prostate cancer cells in vitro and ex vivo. Furthermore, for the in vivo model, blood drawn from TRAMP was tested for CTCs with Ad5/35E1aPSESE4 infection and was positive for CTCs at week 16. Validation was performed on patient blood at various clinical stages and found out 1-100 CTCs expressing GFP upon Ad5/35E1aPSESE4 infection. Interestingly, CTC from one patient was confirmed to be sensitive to docetaxel chemotherapeutic reagent and to abundantly express metastasis-related genes like MMP9, Cofilin1, and FCER1G through RNA-seq.

    Conclusions

    Our study established that the usage of Ad5/35E1aPSESE4 is effective in marking PSA/PSMA-positive prostate cancer cells in patient blood to improve the efficacy of utilizing CTCs as a biomarker.

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