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O4: The value of an immediate intravesical instillation of mitomycin C in patients with non-muscle-invasive bladder cancer: A prospective multicentre randomised study in 2243 patientsBosschieter J., Nieuwenhuijzen J.A., Van Ginkel T., Vis A.N., Witte B., Newling D., Beckers G.M.A., Van Moorselaar R.J.A.
Introduction & Objectives
The effect of an immediate single chemotherapy instillation after transurethral resection (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) is still under debate. Especially if the immediate instillation is followed by an adjuvant schedule of instillations, the evidence is limited. The aim of this study is to compare the effect of an instillation with mitomycin C (MMC) within 24 hours after TURBT to that of an instillation 2 weeks after TURBT, with or without an adjuvant course of instillations.
Material & Methods
A total of 2844 patients with NMIBC were randomized to receive either an immediate (≤24 hours after TURBT) or a delayed single instillation (2 weeks after TURBT) of mitomycin C (MMC), between 1998 and 2003. Patients were divided into three risk groups based on clinical factors and histopathology. The low-risk group did not receive adjuvant instillations, the intermediate risk group received a total of 9 instillations and the high risk group received a total of 15 instillations. Time-to-recurrence and risk-of-recurrence were analyzed with the log-rank test and Cox-regression, incidence of adverse events with the χ² test.
On an intention-to-treat basis a total of 2243 patients were eligible for analysis. The recurrence-risk was 43% and 46% in the LOR-group (5-yr follow-up, p=0.11), 20% and 32% in the IMR-group (3-yr follow-up, p=0.037) and 28% and 35% in the HIR-group (3-yr follow-up, p=0.007) for an immediate and delayed instillation, respectively. Recurrence rates were 27% in the immediate and 36% in the delayed-instillation group (p<0.001) with a 27% reduction in the risk-of-recurrence (hazard ratio: 0.73, 95% confidence interval, 0.63-0.85, p<0.001, multivariable). Incidence of adverse events did not differ significantly between treatment groups (immediate instillation 25%, delayed instillation 22%, p=0.08). The risk groups defined in this study do not correspond with the risk groups used in current guidelines, which is a limitation of this study.
An instillation with MMC within 24 hours after TURBT reduces the recurrence-risk in NMIBC patients, even in patients treated with up to 15 instillations.
P164: Testis tumor: Is LDH more than a volume predictor?Abreu M., Lourenço M.P., Parada B., Figueiredo A.
Introduction & Objectives
Tumor biomarkers are of the utmost importance when diagnosing and staging testicular cancer. However, some refer to them as underutilized. Among the three main biomarkers for testicular cancer, Lactate Dehydrogenase (LDH) is considered the less specific, being mainly considered a predictor of tumor volume. This study aims to identify the relevance of LDH as a predictor of survival in Testicular Germ Cell Tumours (TGCT).
Materials & Methods
Seventy-seven clinical registries corresponding to patients orchiectomized in a tertiary center due to suspect of testicular cancer, diagnosed with TGCT, between January 2010 and November 2016 were studied. For every patient, when available, the pre- and post-operative biomarkers were registered. For post-operative marker stratification, the thresholds of TNM classifications for Serum Tumor Markers were utilized. All studied variables were subjected to normality tests and, as non-normal variables, the correlation test utilized was “Spearman Rank-order Correlation”, provided by SPSS v24.0.
Among the seventy-seven patients, seven died (9.1%). In our sample, there was no correlation between LDH value and tumor size. There was, however, a positive statistically significant correlation between LDH pre-operative absolute values and survival (p<0,01, ρ=0,379). Neither α-fetoprotein nor human Chorionic Gonadotropin (hCG) pre-operative values correlated with survival. Regarding post-operative markers, there was a positive statistically significant correlation between LDH staged by TNM and survival (p<0,01, ρ=0,549), which was stronger than the one attained by hCG (p=0,02, ρ=0,284).
While its low specificity may be considered a hurdle for more complex interpretations, LDH is a readily available biomarker with, as suggested by the results of this series, a potential for predictive interpretations. Therefore, larger studies that validate or result in a better insight of the marker trends should be performed.
P071: Targeting Twist1-Hoxa9 to sensitize prostate cancer to PARP inhibitionMalek R.1, Gajula R.2, Williams R.2, Nghiem B.3, Simons B.4, Wang H.2, Taparra K.2, Barbhuiya M.2, Deweese T.2, Pienta K.4, Hurley P.4, Morrissey C.3, Tran P.2
Introduction & Objectives
Personalized molecular strategies to identify prostate cancer (CaP) patients that are more likely to respond to specific treatment would result in better outcomes and less overtreatment. A recent example is the sensitivity of metastatic prostate cancers to PARP inhibition in only those patients that have defects in DNA damage response (DDR). Recently, acute myelogenous leukemias positive for Mixed Lineage Leukemia (MLL) fusion proteins have been shown to overexpress HOXA9 which in turn leads to increased expression of DDR genes thereby facilitating resistance to PARP inhibitor therapy. Inhibiting HOXA9 resulted in restoring sensitivity of MLL positive AML cells to PARP inhibitors. TWIST1 is a master transcriptional regulator of the EMT that plays key roles during development and can promote cancer metastasis. We have demonstrated that TWIST1 activates transcription of HOXA9 which contributes to the induction of a TWIST1-dependent metastatic phenotype in prostate cancer. Further, we have found that TWIST1 forms a complex with the MLL/COMPASS methyltransferase complex and this complex activates HOXA9 expression by H3K4me3 chromatin modification of the HOXA9 promoter region. The goal of this project is 1) to investigate whether HOXA9 expression occurs along with TWIST1 in vivo and 2) determine whether HOXA9 can lead to expression of DDR genes in prostate cancer and thus, PARP inhibitor resistance and 3) determine whether inhibiting HOXA9 will dampen TWIST1-mediated pro-metastatic responses and sensitize these cells to PARP inhibition.
We found that TWIST1 is expressed along with HOXA9 in the developing prostate with peak expression occurring at ~ E17.5. TWIST1 and HOXA9 are re-expressed in at least one model of mouse prostate cancer. Importantly, we found co-expression of TWIST1 and HOXA9 in a subset of primary CaP tumors in patient samples and their expression was significantly enriched in metastatic samples. Furthermore, alterations in TWIST1 and HOXA9 were associated with decreased survival in patient data from cBIO. In support of our previous data, we show that inhibition of HOXA9 using a peptide inhibitor decreased the pro-metastatic behavior of TWIST1 over-expressing Myc-CaP and PC3 cells in vitro and in vivo.
TWIST1 plays key roles during development and is a master transcriptional regulator of epithelial plasticity programs that can promote cancer metastasis. We demonstrate that HOXA9 may be a target of TWIST1 during development and this phenomenon is reactivated in CaP progression. We show that HOXA9 inhibition can dampen TWIST1-dependent pro-metastatic behavior suggesting that HOXA9 is a potential target for combination therapy in metastatic CaP.
P113: Long term overall survival (OS) in patients with primary metastatic kidney cancer: An analysis of 1468 patients from the Austrian National Cancer Registry (ANCR)Marszalek M.1, Karim-Kos H.2, Madersbacher S.3, Rauchenwald M.1, Hackl M4
Introduction & Objectives
The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of metastatic kidney cancer fundamentally. To elaborate the potential impact of TKI therapies, we studied trends in OS for patients with primary metastatic kidney cancer between 1998 and 2014 in Austria.
Materials & Methods
All patients with primary metastatic kidney cancer aged ≥18 years, diagnosed from 1998-2009 were derived from the ANCR (n=2134). Patients diagnosed from 2004-2006 (n=316) were excluded (transition period of systemic therapies). To evaluate survival differences between patients treated in preTKI-era and TKI-era, two periods were defined: 1998-2003 (before the introduction of Sunitinib in Austria, P1; N=926) and 2006-2009 (P2; N=542). Follow-up was complete until December 31st, 2014. OS rates were estimated by using the Kaplan-Meier method. The Cox proportional hazard model was used to calculate hazard ratios (HR).
A total 1468 patients was included in the analysis. The median age of the study population was 70 yrs (sd ±12) and did not differ between the two eras. The incidence of T1 tumors increased from 6.6% in P1 to 10% in P2 while T4 tumors decreased from 15% to 6.5% (p<.001). Surgery rate remained stable at 48% (p=.14). Five-year OS for patients undergoing surgery slightly increased from 16% in P1 to 20% in P2, although not significant (p=.11). For patients without surgery 5-year OS improved from 4.3% in P1 to 7.9% in P2 (p=.02). Apart from surgery, survival gain was observed for younger patients (<75 yrs) of 4% (p=.04) and for T3/T4 tumors of 7% (p=.008). The risk of death (HR) for patients treated in the TKI-era was reduced compared to the preTKI-era (HR 0.83, 95% CI 0.74-0.93) adjusted for sex, age, T-stage and surgery. Survival advantage for patients undergoing surgery remained significant (HR: 0.50, 95% CI 0.45-0.57) after adjustment for TKI-era, sex, age, T-stage.
Patients with primary metastatic kidney cancer treated in the TKI era show improved OS compared to the cytokine era. Most benefit was observed in non-surgical patients, younger patients and for T3/T4 disease. Surgery remains as an important therapy for additional survival benefit.
P032: Variability within the national registry of active surveillance in prostate cancer in SpainRubio Briones J.1, Borque Fernando A.2, Esteban L.M.3, Martínez-Breijo S.4, Medina R.5, Montesinos M.6, Ramirez M.7, Hernadez V.8, Castells M.9, López P.10, Soto A.11, Gil J.2, Gómez E.12, Medrano P.13, Huguet J.14, Quicios C.15, Fumadó Ll.16, Herrera B.17, Moreno J.18, Torres M.19, Soto J.20, Congregado B.21, Duarte J.22, Rodríguez N.23, Celma A.24, García-Rodríguez J.25, Aguilar A.26, Fernández T.27, Queipo J.A.28, Giménez-Bachs J.M.29, Plata A.30, Ortiz M.31, Rodrigo M.32, Hernández Y.33
Introduction & Objectives
A National Registry in AS (AEU/PIEM/2014/0001, ClinicalTrials.gov Identifier: NCT02865330) supported by the Spanish Urological Association started in April 2014 to recruit patients in AS, allowing different local inclusion criteria and FU strategies. Our present objective is to describe variability in enrollment criteria, resources, and FU strategies with the aim to settle future protocols comparisons
Materials & Methods
A questionnaire (QNR) of local practice on AS reviewed by the Advisory Board, was sent to every Associated Investigator (AI). It was divided in 7 domains: management and experience on AS (1st), inclusion criteria (2nd), initial characterization of PCa (3rd), strategies within the confirmation period (4th), FU protocol (5th), criteria to biopsy (Bx) by event (6th) and criteria to abandon AS (7th).
A total of 33/40 Centers answered (82.5%), representing 1151 patients before April 20th 2016 (95.4%). By domain: 1st) Urology Departments manage AS in 87.9%. Specific QNR such as EPIC, IIEF or IPSS are unusual. 2nd). The upper limits to recommend AS are: 75 years old (85.7%), PSA≤10 ng/mL (75%), cT2a (40.9%), 2 positive cores (59.1%), 5 mm or 50% of core involvement (93.5%), Gleason 6 (72.7%), PSAD is not relevant in 63.6%. 3rd) mpMRI is not used at the initial characterization in 54,5%. PCA3 and 4Ks are used in 2 Centers. In real world, just one dedicated radiologist analyzes mpMRI in 55.2% of Centers, with specific training in just 48.2%. Before the confirmation Bx, 45.2% practice mpMRI 4th) Just 2 Centers practice transperineal approach in confirmation Bx with 20-30cores. In initial Bx, 39.4% perform 10-12 cores and 13-20 in 36.4%. Just one Center uses US-MRI fusion software. 5th) median FU time is 6 months (53.1%). Before FU-Bx, mpMRI is performed in 39.4%. 6th) One center does not contemplate Bx by event, but new suspicious DRE is an indication in 76.7% of the responders. 7th) PSA>10 ng/mL is criteria to abandon AS in 60.6%, but specially in relation to PSA kinetics or anxiety, as is also PIRADS 4-5 in three Centers. Gleason 3+4 progression drives abandon in some cases (50%), but 4+3 in 90.3%. Bilaterality is not a reason to abandon in 68.7%. The presence of ≥ 3 positive cores is considered progression by 96.6% of the responders and percentage of PCa at one core > 50% or > 5 mm in 76.6 and 50% respectively. All the responders consider abandon because patient anxiety. The age limit to switch to watchful waiting strategies is 80 years in 48.5%.
Implementation of AS is heterogeneous in Spain. Mostly strict inclusion criteria are considered. There are more differences in FU strategies and abandon criteria. Real world shows low implementation of mpMRI, new biomarkers, transperineal or fusion Bx due to limited resources. Future research of these different protocols could be extremely relevant to guide us to the best costeffectivenes protocol on AS.
Session: Improved management for urothelial cancer
Location: Thursday 16 November 2017, 15:20 - 16:20, H1
What is an acceptable false negative rate in the detection of prostate cancer?M.J. Roobol, Rotterdam (NL)
Session: Improving effectiveness in diagnosis of prostate cancer - Part 1
Location: Thursday 16 November 2017, 08:35 - 10:00, H1
Are we at the same level? Long term outcome of focal therapy of small renal masses vs. partial nephrectomyS. Joniau, Leuven (BE)
Session: Increasing the performance in the treatment of renal cell cancer
Location: Thursday 16 November 2017, 10:30 - 12:00, H1
P052: Assessment of association between clinical characteristics and prostate specific antigen (PSA) progression in men with prostate cancer receiving a leuprorelin acetate implant: results from the non-interventional German cohort LEAN studySchmitz-Dräger B.2, Mühlich S.3, Ottillinger B.1, Studen M.4