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178 Abstracts

  • Introduction & Objectives

    1. Compare the recurrence and progression-free survival  among patients treated and untreated with post-TUR chemotherapy.
    2. Determine the target population with NMIBC potentially beneficiary of MMC post-TUR.

    Material & Methods

    Non experimental longitudinal prospective study of 349 consecutive patients with NMIBC subsidiary of MMC post-TUR in the Jerez Hospital between 2010-2013. Potential predictors of efficacy of MMC post-TUR in our series were analysed: Age, gender, smoking quit at the time of diagnosis, early recurrence.

    Results

    The average rate of patients included in the program is 53.9%, an increase of 79.3% (p <0.001)
    at 3 years.  Mean follow-up 26.3 ± 0.7 months. Mean time to first recurrence significantly higher in the
    MMC post-TUR group receiving [43.5 months (95% CI, 40.7 to 46.3) vs 38.5 months (95% CI, 35.5 to 41.6); p <0.05].  The absolute risk reduction of recurrence with MMC post-TUR is 14.5% (95% CI, 5.9 to 23.5%, p <0.001), and the number of patients needed to be treated (NNT) of 6.9 (95% CI, 4.3 to 17.9 P <0.001).  The statistical analysis of the exposed cohort to MMC post-TUR (n = 164) and unexposed (n = 185) results that the MMC post-TUR is effective in reducing the risk of recurrence in tumours PTa-1, low-high grade, single-multiple, ≤ 3cm maximum diameter, with no history of bladder tumours in the 12 months prior, with a sample of muscle layer in the TUR, and  without pretreatment with MMC.

    Conclusions

    MMC decreases the percentage of tumour recurrence in NMIBC, and increases disease-free time. The MMC increases disease-free time in all prognosis recurrence groups. The effectiveness of MMC post-TUR in our country is similar to that reported by other groups. Our findings suggest a potential benefit of MMC post-TUR in all patients with primary NMIBC or without early relapse, ≤ 3cm without prior treatment with intravesical MMC.

  • Introduction & Objectives

    Su is a standard tx for mccRCC. Data on its activity in the rare variant of mchRCC, is limited by very small or heterogeneous (mixed histology with papillary type, or mixed targeted therapies) studies. We analysed the activity of Su in a relatively large and homogenous international cohort of mchRCC pts, in terms of outcome and comparison to mccRCC.

    Material & Methods

    Records from mchRCC pts treated with 1st line Su in 9 centers across 4 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and outcome were performed. Subsequently, mchRCC pts were individually matched to mccRCC pts. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS) between the groups.

    Results

    Between 2004-2014, 33 pts (median age 64, 45% male) with mchRCC were treated with Su as 1st line tx. 76% had a prior nephrectomy. HENG risk was good 27%, intermediate 55%, and poor 18%. 33% were active smokers, and 30% users of angiotensin system inhibitors (ASIs). 55%, 27%, and 33% had lung, liver and bone metastases, respectively. 48% had a pre-tx neutrophil to lymphocyte ratio (NLR) >3. 42% had dose reduction/tx interruption (DR/TI). Su induced hypertension (HTN) occurred in 48%. 75% achieved a clinical benefit (partial response + stable disease), while 25% had disease progression within the first 3 months of tx. Median PFS and OS were 10 and 26 months, respectively. Factors associated with PFS were the HENG risk (HR 3.8, p=0.025) and pre-tx NLR >3 (HR 0.6, p=0.012). Factors associated with OS were the HENG risk (HR 4.27, p=0.027), liver metastases (HR 4.6, p=0.029), and pre-treatment NLR < 3 (HR 0.5, p=0.04). Tx outcome was not significantly different between mchRCC pts and mccRCC pts, who were individually matched by HENG risk, nephrectomy/smoking status, pre-tx NLR, use of ASIs, DR/TI, and Su induced HTN. In mccRCC pts (p value versus mchRCC), 70% achieved a clinical benefit (p=0.58), and median PFS and OS were  9 (p=0.7) and 24 (p=0.6) months, respectively.

    Conclusions

    In mchRCC pts, Su tx may have similar outcome to mccRCC pts.

  • Introduction & Objectives

    Collection of data in daily clinical practice on the efficacy and safety of Degarelix in the treatment of patients with prostate cancer (PCa).

    Material & Methods

    Data of 1,010 Degarelix patients were collected. During the assessment, previous treatment, concomitant medication, stage and grade of tumour as well as alkaline phosphatase, testosterone and PSA-value, side-effects, and overall survival were documented. At the time of this assessment the maximum follow-up was 48 months.

    Results

    The median overall survival was not yet reached. The 75% threshold for overall survival was reached for all patients after 149 weeks (176 vs. 132 weeks in the sub-groups of hormone-naive patients and patients with previous hormone treatment, respectively, Fig. 1).

    In the sub-group of patients with previous LHRH agonist therapy, the median time to PSA progression was shorter (30 weeks, 75% threshold) than in the group without previous LHRH therapy (88 weeks, 75% threshold, Fig. 2). A higher proportion of patients with previous LHRH therapy experienced PSA progression (25%, n=114) as compared to patients without previous LHRH therapy (15%, n=86).

    In the sub-group of metastatic patients, the median progression-free survival was 141 weeks. The median follow-up of the whole patient population was 128 weeks (32 months).

    The mean prostate volume decreased from 37 ml at the beginning (n=85) to 30 ml after 3 months (19% decrease, n=25) and 26 ml after 6 months (30% decrease, n=16).

    The most frequent side-effects were hot flushes (12.87%), erythema at the injection site (8.5%) and fatigue (5.25%).

     

    Conclusions

    Efficacy and safety of Degarelix were confirmed in routine daily practice. The median survival was not yet reached. The 75% threshold for the overall survival was reached after 37 months. Thus, these values are already above those reported in scientific literature for LHRH agonists at 25-31 months.

  • Introduction & Objectives

    Peyronie's disease is characterized by formation of hardened scar and fibrous tissue in the tunica albuginea, septum and corpora cavernosa of the penis. Its typical symptoms are the painful bend during erection, which makes sexual intercourse difficult and palpable plaque or tough "cord"  on the dorsal side of the penis. Proper evaluation of the plaque's location and size is important in the choice of treatment method and in the evaluation of the effects of instituted treatment.
    3D ultrasound transducers enable to obtain three-dimensional images and make the evaluation of the examined organ more accurate.
    The aim of this study was to present the examination methods, indications and advantages of three-dimensional ultrasound in the diagnosis of induratio penis plastica (Peironie' s disease) and assessment of the effects of treatment.

    Material & Methods

    3D ultrasound scanning was performed in twelve patients with Peyronie's disease with palpable plaques in the tunica albuginea of the penis. The scanning was carried out with a linear transducer (ultrasonic wave frequency of 12 MHz) positioned transversely to the long axis of the penis and then moved from the root of the penis towards the glans penis. During movement of the transducer, single ultrasound images are obtained and arranged to give an appearance of a three-dimensional image.

    Results

    We obtained the ultrasound images, encoded as "volumetric units", or voxels, and arranged to form a cube, which was later computer-processed, using a specially designed computer program. In addition to traditional longitudinal and transverse views, it enabled to obtain also a coronal view. In patients with Peyronie's disease, this third view is of great importance since it allows for visualization of the whole plaque. Careful image analysis performed after the examination (not in the patient's presence) allowed to identify other, smaller plaques which were not observed prior to examination.

    Conclusions

    l. 3D ultrasound diagnosis allows for more accurate evaluation of pathologic changes in the tunica albuginea of the penis in Peyronie's disease.
    2. Final evaluation involving analysis of obtained images is done after the examination and not in the patient's presence.
    3. Examination time is shortened when compared with two-dimensional ultrasound.

  • Introduction & Objectives

    Mortality from cancer appears to be due to a complex of demographic and clinical factors of which insurance is a part.
    We looked at 257 patients undergoing radical cystectomy and compared their presenting characteristics and their mortality rates, all cause, disease specific and progression rates between those treated in the national health service (NHS) and those with private health insurance (PHI).

    Material & Methods

    Various characteristics were compared using Fishers and t tests.
    Kaplan Meier curves were generated for the two cohorts for progression and mortality and logistic regression applied to generate significant predictors. The operations were all performed by the same surgeon.

    Results

    Characteristic NHS n = 225 PHI n = 32 P
    Age years 68 64 0.026
    Tumour volume cc 22 11 0.18
    Positive surgical margins 32 (14%) 2 (6%) 0.27
    Stage localised
              Locally advanced
    146 (56%)
    99 (44%)
    20 (62%)
    12 (38%)
    0.84
    Carcinoma in situ 92 (41%) 19 (59%) 0.057
    Mean number of nodes dissected 9 13 0.006
    Patients with nodal involvement 43 (19%) 7 (22%) 0.811
    Nodal extracapsular extension 24/43 4/7 1.0
    Complications 89 (40%) 4 (13%) 0.002
    Additional treatment given 38 (17%) 4 (13%) 0.79
    Neobladder 40 (18%) 12 (38%) 0.16

     
     

    All cause mortality      
      coefficient P Odds ratio
    Neobladder -0.8 0.0154 0.42
    Private patient -1.4 0.0013 0.24
    T3 1.007 0.0008 2.7
    T4 1.97 <0.0001 7.18
    Disease specific mortality      
    Additional treatment 0.77 0.021 2.17
    Complication 0.73 0.013 2.08
    Neobladder -0.95 0.015 0.38
    Node density 2.26 0.014 9.67
    Private patient -1.08 0.035 0.33
    Progression      
    Additional treatment 0.74 0.029 2.11
    Private patient -1.92 0.002 0.14
    T2 1.18 0.010 3.28
    T3 1.99 <0.0001 7.3
    T4 1.89 0.0001 6.6

    Conclusions

    The PHI cohort generated negative protective coefficents on all three survival analyses.
    PHI younger, with more nodes taken during nodal dissection and have less complications.
    Regarding prognosis, PHI was a significant protective risk variable for ACM (OR 0.24),  DSM (OR 0.33) and PFM (0.14).
     
    Also (but not statistically significant), those with PHI had smaller tumours, less PSM, less locally advanced disease, less additional treatments (adjuvant, neoadjuvant, radiotherapy and chemotherapy), more neobladders and more CIS.
    However, stage, additional treatment and neobladder were all significant predictors of survival. These were all favourable in those with PHI.
     
    The higher ACM may be due to overall poorer health, more comorbidities, unhealthy behaviour? Inadequate preventive health care, poor management of chronic conditions, barriers to receiving treatment, inability to navigate health care system, high cost, misinformation and distrust of healthcare system, lack of transport, lack of time off work. Lower quality of treatment offered by providers  serving Medicaid and uninsured. Further, there is no lead time bias (perceived increased survival time with no effect on course of cancer) with bladder cancer as there is no screening protocol, unlike prostate.
     
    This study shows significant differences in prognosis post cystectomy to those treated in the NHS and those treated privately.

  • Introduction & Objectives

    The introduction of new life-prolonging treatments including docetaxel (D), cabazitaxel (C), abiraterone (A) and enzalutamide (E) have revolutionised the outcomes of patients with mCRPC. Treatment sequences remain variable dependent on physicians’ choices. The aim of this study is to evaluate outcomes in patients receiving cabazitaxel and its’ potential relevance on therapeutic sequencing.

    Material & Methods

    A retrospective study of mCRPC patients treated with cabazitaxel after progression during or following docetaxel at one centre in England. Data on thirty three patients relating to patients’ characteristics, treatments and clinical outcomes were collected from the medical records and anonymised for analysis.

    Results

    Thirty three patients analysed received a median (range) of 3 (2-4) different life-prolonging therapies. The median (interquartile range, IQR) age of patients commencing on cabazitaxel was 71.1 (67.4 – 75.1) years. Cabazitaxel was second line therapy after docetaxel in 22/33 (67%) patients. Median (IQR) time from mCRPC diagnosis to start of cabazitaxel was 1.5 (1.0-2.0) years. 

    Number of life-extending drugs Median [95% CI] OS from mCRPC diagnosis
    2 DC: N=7, 29.4 months [21.4-80.1]
    3 DAC: N=7, 26.2 months [22.1-40.4]
    DCA: N=15, 40.0 months [24.3-57.6]
    4 N=4, 32.1 months [15.1-.]


    The tabulated data describes the number of treatment used with the following sequences: 7 patients received 2 therapies (DC); 22 patients received 3 therapies (DAC: n=7; DCA: n=15); 4 patients received 4 therapies (DCAE: n=1; DACE: n=1; DCEA: n=1; DAEC: n=1). Overall survival was longer, with a 14 months addition in patients receiving second-line cabazitaxel compared to third-line following docetaxel and abiraterone.

    Conclusions

    Based on this one centre real-life practice sequencing data, there is evidence to suggest that cabazitaxel has optimal benefit on overall survival when used second line following docetaxel. This data is promising and may be the beginning to unlocking the sequencing conundrum. A multi-centre study is being carried out to validate this data further.

  • Introduction & Objectives

    Ablative therapies like cryotherapy (CR) and radiofrecuency (RF) are an alternative for treatment of small renal solid masses (SRSM) in patients with a high surgical risk, severe comorbidities, chronic renal failure or in selected patients with bilateral renal tumours and tumours in patients with solitary kidney. The objective of this study is to analyse the efficacy, complications and oncologic results of SRSM treatment through CR or RF.

    Material & Methods

    46 patients with SRSM diagnosed by contrast-enhanced computed tomography (CT) or contrast-enhanced ultrasound (US) and treated by CR or RF between May 2006 and December 2014 were retrospectively analysed. SRSM was defined as a solid renal mass smaller than 4 cm at ultrasound (US) or computed tomography (CT).
    The parameters analyzed were: Age, sex, tumour size and location, surgical approach, complications by Clavien-Dindo classification, treatment failure and mortality. The follow-up was performed by a combination of CT and US in 36 patients, and only by CT in 10 patients.
    Tumour persistence and local recurrence were defined as the presence of increased uptake of contrast in either of image studies (US or CT).

    Results

    39 patients (84.8%) were treated by CR and 7 patients (15.2%) were treated by RF. The median follow up period was 34 months (range 3-107). Table 1 shows the sample characteristics.

    Table 1. Characteristics of the sample.
      MEDIAN RANGE
    AGE 74 40-85
    Nº OF PROBES 2 2-4
    TUMOUR SIZE (cm) 2.8 3.5
      N %
    TUMOUR LOCATION
    Right kidney
    Left kidney
     
    25/46
    21/46
     
    54.4
    46.6
    SURGICAL APPROACH
    Percutaneous
    Laparoscopic
    Open surgery
     
    38/46
    7/46
    1/46
     
    82.6
    15.2
    2.2

    Previous biopsy to the ablative treatment was performed in 34 patients (73.9%), in 17 patients the biopsy was informed as malignant tumour, in 5 patients were informed as benign tumour and in 12 patients the biopsy was non-conclusive.
    Table 2 shows the complications and the persistence of the renal mass.

      N CLAVIEN-DINDO TREATMENT
    COMPLICATION
    Haematoma
    Active bleeding
    Urinary fistula
     
    7
    1
    1
     
    I
    IIIa
    IIIb
     
    Conservative
    Embolization
    Surgery
    TOTAL 9 19.6%  
      N PERCENTAGE  
    PERSISTENCE RENAL MASS
    Total
    Active Surveillance
    Cryoablation
    Surgery
    Decease
     
    12
    5
    2
    4
    1
     
    26.1%
    10.9%
    4.3%
    8.7%
    2.2%
     

     
    The persistence of the renal mass was higher in the group of patients treated by RF compared with the group of patients treated by CR (42.9% Vs 23.1%), although this difference was not statistically significant.
    During the follow up period 4 patients died, 1 patient died due to renal cancer progression and 3 died by other causes.

    Conclusions

    Tumour ablation by CR or RF is an effective and safe treatment of SRSM. Due to a lower complications rate, these ablative therapies could be considered an alternative to the classic surgical treatment of SRSM in selected patients.

  • Introduction & Objectives

    To assess temporal tends in radical cystectomy (RC) and pelvic lymph node dissection (PLND) in the Netherlands between 2006 and 2012.

    Material & Methods

    This nationwide, retrospective, population-based study included clinical stage I-III bladder cancer (BC) patients (cT1-4aN0M0) from the Netherlands Cancer Registry who underwent RC as primary treatment for urothelial carcinoma between 2006 and 2012. Performance rates of PLND at RC, median lymph node count (LNC) and rates of positive nodal (pN+) disease were determined per year and their relation with pN+ disease during the study period was analysed. Furthermore patient and hospital characteristics associated with the performance of PLND at RC were identified.

    Results

    In total, 3678 patients were included. Mean age was 66.7 year and 75.6% (n=2780) were male. Of all RCs, 49.8% (n=1833) was performed in non-teaching hospitals. Clinical stages of disease were evenly distributed over the study period. Ninety percent (n=3312) underwent RC plus PLND, with a median LNC of 10. Performance rate of PLND increased from 82.9% in 2006 to 95.6% in 2012 (p<0.001), median LNC increased from 6 to 12  (p<0.001) and the amount of pN+ disease increased from 17.4% to 23.0% (p<0.001), table 1. In academic hospitals (and 2 cancer centers) PLND was only omitted in 5.5%, vs. 9.5% and 12.4% in teaching and non-teaching hospitals, respectively (p<0.001). Median LNC was 15.0 in academic hospitals vs. 10.0 and 9.0 in teaching and non-teaching hospitals, respectively (p<0.001). Multivariate logistic regression analysis revealed females (Ref. male) and elderly patients (>70yr.) (Ref. <50yr.) were less likely to receive a PLND. Patients operated in academic hospitals were more likely to receive a PLND (Ref. non-teaching hospital), as well as those operated after 2007 (Ref. 2006). All p20/ yr.) did not influence the chance of receiving PLND. Limitations: Extent of PLND was not registered. 

    Table 1. Distribution of clinical stages of disease and the performance of PLND, with corresponding median lymph node counts and rate of node positive disease over time.

      2006 2007 2008 2009 2010 2011 2012 P-value
    RC, N 424 419 522 510 524 588 537 -
    Clinical stage I, % 11.3 14.3 13.4 13.3 9.5 13.6 12.4 0.088 (Chi-square)
     
     
    Clinical stage II, % 73.3 74.7 73.0 70.6 75.6 71.6 75.6
    Clinical stage III, % 15.3 11.0 13.6 16.1 14.9 14.8 13.4
    PLND, %
     
    82.9 84.3 89.9 88.3 91.1 95.4 95.6  
    Median LNC 7.0 8.0 9.0 9.0 11.0 13.0 12.0  
    pN+, %
     
    17.4 17.4 19.5 20.6 21.1 20.2 23.0  

    Conclusions

    In the Netherlands, the performance of PLND at RC and LNC has significantly increased during the period 2006 and 2012. This suggests improved pathological staging of clinical stage I-III BC. 

  • Introduction & Objectives

    Granulomas are inflammatory character nodulillares formations, consisting essentially of macrophages. There are several diseases that still under study mechanisms granulomatous reactions occur at different locations, including the genitourinary system, constituting a diagnostic challenge to the urologist.

    Describe through clinical cases presented to our urology department, radiological findings in granulomatous diseases that tend to generate diagnostic uncertainty with consequent clinical implication.

    Material & Methods

    Systematic study by plain radiography, ultrasound, computed tomography and nuclear magnetic resonance cases presented in our service as the testicular sarcoidosis and genitourinary tuberculosis.

    Results

    Sarcoidosis is a chronic disease of unknown etiology, characterized by noncaseating epithelioid granulomas in multiple organs and tissues. 
    Bilateral hilar lymphadenopathy is the most common radiographic finding. 30% of patients present with extrapulmonary disease, including the genitourinary system. Injuries to testicular level is a real challenge differential between tumour masses. In the case presented objectify as testicular lesions are characteristic, multiple hypoechoic and small. When the masses are in patients with confirmed sarcoidosis, sarcoidosis testicular possible should always be considered, because it can prevent unnecessary orchiectomies. Genitourinary tuberculosis is an important but unusual location, but is the second form of extrapulmonary tuberculosis. Diagnosis is difficult and often delayed because tuberculosis can mimic many other diseases. Imaging studies are very useful to detect the presence of tuberculosis and to monitor response to treatment. This review illustrates the radiological findings in genitourinary tuberculosis in patients with laboratory confirmation of the disease.

    Conclusions

    Granulomatous disease with genitourinary involvement are rare, and can simulate many of the diseases affecting the urinary tract, so it will be a diagnostic challenge for the urologist, which will require knowledge of the key findings in tests image of these institutions.

  • Introduction & Objectives

    Metastatic seminoma is the paradigm of a curable cancer. Pure seminomas stages II with bulky disease and stages III are generally treated with platinum-containing chemotherapy. BEP (bleomycin, etoposide and cisplatin) is the standard treatment. After chemotherapy, patients are evaluated with a CT scan. If there is found a residual tumour >3cm, a PET scan is recommended. A negative PET warrants follow-up. In a positive PET lesions must be regarded as harbouring viable tumour and should be resected, if technically possible.
    We want to evaluate the radiological responses to chemotherapy in pure seminomas, how residual mass dimension influenced our clinical decisions and the number of unnecessary procedures due to false-positive results on PET.

    Material & Methods

    This retrospective study involved two Centers: Institut Català d'Oncologia - l'Hospitalet and Hospital de Santa Maria. The authors reviewed patients’ files with pure seminoma stages II and III treated with BEP or EP from 1996 to 2014 to evaluate the type of responses to chemotherapy and the clinical decisions in front of residual masses.

    Results

    Fifty patients with pure seminoma stages II and III were eligible for evaluation. The median age was 36 years old (range 22-54). The median follow-up was 4.3 years. All patients had primary testicular seminoma except two that had primary mediastinal disease. Forty three patients had stage II and seven had stage III disease. All patients belong to good IGCCCG prognostic group except two. Thirty four patients had been treated with BEP and sixteen with EP. Twenty six patients (52%) had radiological complete response and were disease free in the last follow-up. Twenty four patients (48%) had partial response. The median diameter of the residual masses was 2.8cm (1-15). A PET was performed in fourteen patients (28%) with residual masses above 2cm. The median time between ending chemotherapy and PET evaluation was 6 weeks. PET was positive in four patients. The median SUV was 6.5 (2.5–7.6). One patient had inoperable disease and is in surveillance without disease progression. The other three were operated but only one had viable tumor. There were no long term chemotherapy or surgical related complications. The three patients with residual masses between 2 and 3cm had negative PET. Two patients with negative PET have progressed after 10 and 15 months. They were treated with TIP (paclitaxel, etoposide and ifosfamide) and surgery and are currently free of disease. Two patients with retroperitoneal masses above 3cm undergone surgery without having done a PET. There was no viable tumor. Eight patients had residual masses with less than 2cm and are free of disease.

    Conclusions

    Patients with metastatic seminoma treated with chemotherapy have a high percentage of cure. PET is actually the better tool to guide clinical management of residual tumors, particularly for surveillance. In our population there was no benefit to do a PET for lesions <3cm. Due to some false-positive PET results, some patients were overtreated. It is important to optimize the selection of patients for surgery.

  • Introduction & Objectives

    Since the introduction of tyrosine kinase inhibitors (TKI) in the treatment of metastatic renal cell carcinoma (RCC), prognostic of these patients was significantly approved and a few cases achieved a complete response (CR). However, the benefit of a maintenance treatment, taking into account the cost and tolerance, remains unclear. The purpose of this study is to evaluate and compare the outcome of six patients achieving a complete response on TKI after treatment discontinuation or maintenance.

    Material & Methods

    A retrospective analysis of patients with metastatic renal cell carcinoma who obtained complete response during treatment with TKIs (sunitinib or sorafenib). From a series of 27 patients treated in our department in first line, six patients were identified in complete response on TKI according to RECIST criteria. Median age 64,5 y (range : 49-79y). All with intermediate MSKCC prognosis and received an initial nephrectomy followed by a first line treatment by Sunitinib (n=5 ) or Sorafenib (n=1) . The median number of cycles of TKI to achieve CR was 9 (range : 4 to 17 cycles).

    Results

    Among the six patients who achieved CR with TKI, only one patient don’t interrupt TKI treatment after complete response (26 cycles of sunitinib ongoing to date with a persistent CR), whereas treatment was interrupted in 5 patients  at complete response (1pt) or after further cycles of the same TKI (11 cycles on average). Two of the 5 patients who stopped treatment still in CR (24 & 6 months of follow up). For the 3 other patients, local and or metastatic relapse occurred at 6, 13 & 18 months of treatment interruption. The treatment of relapsing disease was resumption of TKI (sunitinib : 2 pts, Sorafenib :1 pt) preceded by surgery in one case and resulting in a partial response for tow patients and a new complete response for one patient treated with sorafenib.
    Because of a significant early observed toxicity (hypertention , hypothyrreosis, fatigue , thrombopenea and hand & food syndrome ), dose of TKI was reduced after a median of 5 cycles.

    Conclusions

    Parameters associated with achievement of CR are not yet well defined, and we could not define any predictive factors to either stop or give additional cycles of TKI. As such, further research is also needed to identify factors to aid selection of patients who would be at less risk of recurrence after discontinuation of treatment.

  • Introduction & Objectives

    68Ga-DKFZ-11 (68Ga-PSMA) has been suggested as a novel tracer for detecting of PCa relapses and metastases. However there is a limited number of publications about the timing of PSMA PET/CT scan. The aim of the study is to evaluate the diagnostic value of PSMA PET/BT in the diagnosis of recurrent prostate cancer with low PSA levels.

    Material & Methods

    We performed a retrospective analysis in patients who underwent PSMA PET/CT from November 2013 to December 2014 in our department. 53 out of 178 patients who had rising PSA levels (still lower than 5ng/ml), and did not have known metastasis were included in this study.

    Results

    Patients had an average PSA of 1.41 ng/ml. A total of 31 patients (58%) showed at least one extraprostatic or prostatic lesions. Intense pathologic radiotracer uptake was observed in 15 patients (28%) at the site of primary tumor. Lymph node metastases were detected in 19 patients (36%) and bone metastases were detected in 8 patients (15%). A PET positivity rate of 31% (n=4), 54 % (n=13) and 88% (n=14) observed in patients with PSA level of <0.2, 0.2-2 and 2-5 ng/ml respectively. Those with PSA level PSA <0.2, 0.2-2and 2-5 ng/ml had 8% (n=1), 21% (n=5), 56% (n=9) local recurrence 15% (n=2), 42% (n=10), 44% (n=7) lymph node metastasis and %15 (n=2), 8% (n=2), 25% (n=4) bone metastasis. A positive correlation observed between positivity rate and gleason scores (%15 for Gleason 6, %55 for Gleason 7, 75% for Gleason 8 and 77% for Gleason 9). PSMA PET/CT positivity’s confirmed with biopsy (n=3), follow-up (n=26) and conventional imaging studies at the time of the PET/CT (n=11) or during follow up (n=13). According to patient-based analysis of 44 cases %57(n=25) of patients had true positive, %23(n=10) of patients had true negative, %2(n=1) patient had false positive, %18(n=8) of patients had false negative findings which are leading to a sensitivity of 58.1% (95%CI:42.1-72.9%) specificity of 90% (%95CI:%48.6- 98.5). Within the patients who had PSA levels from 0.2 to 5, the sensitivity was %79.3 (%95 CI: %60-91.9).

    Conclusions

    PET/CT with 68Ga PSMA is a valuable tool for assessing recurrence of PCa with a high sensitivity (%79.3) within the patients who has PSA levels between 0.2-5 ng/ml. Additionally PSMA PET/CT can be used in patients with very low (

  • Introduction & Objectives

    In patients with a prostate specific antigen (psa) failure after radical treatment for prostate cancer ,PET/CT with [11C]choline may accurately detect the presence of recurrence.
    Prostate pathology studies suggest in many cases a dominant cancer focus exists within the gland and may be a driver of the aggressiveness of the cancer and the epicenter of recurrence following radiotherapy treatment.
    We investigated the role of integrated [11C]choline PET/CT for target volume selection and delineation  in patients with recurrent prostate cancer following EBRT for a salvage focal Cyberknife Stereotactic Hypofractionated Radiotherapy (SBRT) treatment.

    Material & Methods

    From December 2012 through October 2014 a cohort of 16 patients with a median age of 76 years (range 64 -84) and an history of second locally-recurrent prostate cancer following first salvage Cyberknife SBRT in biochemical relapse after external beam radiotherapy treatment were referred to our department for a focal salvage Cyberknife SBRT.
    Primary EBRT radiotherapy doses ranged from 74 to 79.2 Gy (median 76 Gy) while Cyberknife Sbrt salvage treatment doses ranged from 30-35 Gy in 5 fractions.  The median pre- focal Ck reirradiation PSA was 4,46 ng/ml (range,1,23 -13,04 ng/ml). To reconstruct CTV and organ at risk, CT scan and MRI with T1-T2 sequences were performed and [11C]choline PET/CT images were fuse for focal prostate  target volume definition and delineation.
    In 4 patients focal Cyberknife sbrt treatment consisted of 3 fractions of 10 Gy (total Dose 30 Gy), in the other 12 patients 3 fractions of 12 Gy for a total dose of 36 Gy were delivered. The [11C]choline PET/CT median prostate node volume was of 14,3 cc (range 5,75-65,04).

    Results

    The focal salvage Cyberknife treatment was well tolerated without any rtog grade 3 acute or late toxicity. With a median follow up of 11 months (range 3-22) we observed the following results: No in field recurrence, resulting in a local control of 100%. In 3 patients, respectively at 11, 13 at 21 months after Ck focal treatment we observed a biochemical relapse, a [11C]choline PET/CT detect the presence of a new  local recurrence outside the irradiated field requiring a third Cyberknife focal salvage treatment.

    Conclusions

    In clinical practice, advances in modern imaging show promise for improved detection and characterization of prostate cancer at the different stage of its management including diagnosis, staging treatment planning and follow up. According to available literature [11C]choline PET/CT is not clinically recommendable to plan target volume, nevertheless, our promising data suggest a potential role of [11C]choline PET/CT as an image guide tool for the irradiation of focal prostate cancer relapse. Prospective trials are needed to better define the role of differential prostate treatment on imaging defined GTVs.

  • Introduction & Objectives

    In recent years, nephron-sparing surgery has replaced radical nephrectomy as the treatment of choice for patients with localized renal cell carcinoma (RCC). Oncological outcomes appear to be similar, with less reduction in renal function. Although initially reserved for T1a tumours and imperative indications, partial nephrectomy is now being performed in patients with larger renal masses, when feasible. The aim of this work is to compare laparoscopic versus open partial nephrectomy for the treatment of >4cm RCC.

    Material & Methods

    The authors retrospectively evaluated a group of 81 patients who underwent open or laparoscopic partial nephrectomy for >4cm RCC between January 2005 and June 2015 in a single department. Patient demographics, clinical symptoms, histopathologic factors, intraoperative and postoperative data were compared between the 2 groups. Statistical analysis was performed using SPSS V20.0.

    Results

    A total of 38 (46.9%) laparoscopic and 43 (53.1%) open partial nephrectomies were performed for tumours > 4cm, during the aforementioned period. 62 (76.5%) patients were males and 19 (23.5%) females, with a mean age of 61±1 years, ranging between 26 and 88 years. Most of them were asymptomatic (76.5%) and the most prevalent symptom was flank pain (8.6%). The mean tumour size was 5.48±0.19cm (4.1-16 cm). Pathological stage T1b, T2a, T3a and T3b was found in 66 (81.5%), 6 (7.4%), 8 (9.9%) and 1 (1.2%) of cases, respectively. The majority of tumours were of clear cell histology (49.4%) and Furhman grade 2 (49.4%). There were no statistically significant differences in demographics, presenting symptoms and histopathological factors between the 2 groups. Laparoscopic approach was more often performed in the five latest years (p=0.034). Tumour size was comparable in both open and laparoscopic surgeries (p=0.337), but there were significantly more endophytic tumors in the open surgery group (p=0.05). The mean operative time was 132±6.9min for open surgery and 151±7.2min for the laparoscopic group (p=0.05). Blood loss and warm ischemia time in open surgery (334±62.0mL and 16.6±1.4min) did not differ significantly from laparoscopic approach (307±44.9mL and 19.7±1.0min; p=0.727 and p=0.099, respectively). In the postoperative period, the overall complication rate was 25.9%. Urinary fistula was the most common complication (14.8%), and was not significantly different in both types of surgery (p=0.307). According to the Clavien-Dindo classification, the number of patients with grade 3, 4 and 5 was 13 (16.1%), 1 (1.2%) and 1 (1.2%), respectively. Nephrectomy due to persistent urinary fistula was performed in 1 (1.23%) following laparoscopic and in 6 (7.4%) following open surgery (p=0.761). The length of hospital stay was 7.4±1.3 days and 5.3±0.4 days following open and laparoscopic partial nephrectomy (p=0.137), respectively.

    Conclusions

    For renal tumours larger than 4cm, partial nephrectomy can be performed whenever technically possible with good results and acceptable complication rates. Our data suggest that laparoscopic technique is an effective, minimally invasive therapeutic approach, with no significant increase in warm ischemia time, intraoperative or postoperative surgical complications compared with open surgery. It also has the advantage of an earlier hospital discharge (although not statistically significant in our series).

  • Introduction & Objectives

    Inflammation plays a significant role in development and progression of various solid tumours including prostate cancer. A high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. We assessed the prognostic role of pretreatment NLR Ratio in metastatic castration-resistant prostate (mCRPC) patients treated with Abiraterone.

    Material & Methods

    Patients treated with Abiraterone 1g daily with Prednisolone 10mg daily were identified from the chemotherapy prescribing system (Chemocare). 149 consecutive patients treated between Jan 2012 and May 2014 were identified. We calculated NLR using pre-treatment baseline bloods and assessed whether this affected their response to abiraterone and overall survival.

    Results

    All patients were performance status of 0 or 1. For the whole population median age was 75.1 years (Range=54.9-88.1); median PSA was 52.3 (Range=0.03-6884), and median NLR was 3.05 (Range 0.8-32.4). Median PFS was 6 months (Range 20 days-31 months) and median survival has not been reached. Based on literature review, a NLR cut off of 4 was adopted. There were 99 patients with an NLR 4. Baseline characteristics in the NLR 4 were well matched in terms of median age (75.6yrs vs 73.8yrs) and median baseline PSA (49.8 vs 56.8). More patients pre-treated with Docetaxel chemotherapy had a high NLR of >4 (48% vs 31.3% vs p=0.046).
     
    More than half (50.7%) of patients achieved ≥50% decline in prostate-specific antigen (PSA). There was no significant difference in response between groups with high and low NLR (53.5% vs 44.9% p=0.32). There was no difference in progression free survival between the groups (6 months) however there was a significant difference in overall survival (OS), with the better OS in the lower NLR group compared to the high NLR group (Not reached vs 17.1 months, p=0.05).
     
    On univariate analysis of baseline variables (age, PSA, haemoglobin and alk phos), only alkaline phosphatase level correlated significantly with PFS and OS time (weak negative correlation, r=-.25, p.002 & r=-0.331, p=0.02). Type of metastases was not predictive of survival in this cohort. When controlled for NLR, there were no differences in PFS, OS or PSA response in patients previously treated with Docetaxel pre-treated versus Docetaxel naïve patients.

    Conclusions

    NLR is an inexpensive, readily available prognostic factor and a high NLR predicts poorer overall survival. But NLR is not a predictive factor for treatment response to Abiraterone in both pre and post Docetaxel setting. Hence NLR is unlikely to aid the clinician in sequencing of hormone therapy and chemotherapy in routine clinical practice. Poor prognostic patients with high NLR do not need to be preferentially treated with Docetaxel chemotherapy.

  • Introduction & Objectives

    Heat shock protein 27 (Hsp27) is over-expressed in bladder cancer (BC) and postulated to increase tumour growth, metastasis, and chemotherapy resistance. Apatorsen (A; OGX-427), a novel antisense oligonucleotide, inhibits Hsp27 production and can potentially enhance the efficacy of chemotherapy. This trial was designed to evaluate efficacy and safety of A in combination with gemcitabine and cisplatin (GC) in patients with advanced BC.

    Material & Methods

    Chemotherapy naïve patients with advanced BC were randomized to GC+A 600 mg, GC+A 1000 mg, or GC + placebo. Patients were stratified by Karnofsky performance status (KPS) and visceral disease. The primary endpoint was overall survival (OS). Prognostic sub-groups were retrospectively evaluated using multiple variable modelling and hierarchical step down. A post hoc analysis was performed to explore the hypothesis that Hsp27 inhibition might be relevant to OS in poor prognosis disease.

    Results

    A total of 179 patients were randomized/treated. Median OS was 15.2 months (m). When compared to GC + placebo, GC+A 600 demonstrated improved OS and PFS (OS HR = 0.856 and PFS HR = 0.830) versus GC+A 1000 (OS HR = 0.898; PFS HR = 0.927). Results from the post hoc model revealed that KPS, liver metastasis, alkaline phosphatase, and hemoglobin were prognostic. A median prognostic score dichotomized patients into poor and good prognosis groups (50% each group). Patients with poor prognosis treated with GC+A 600 had a greater reduction in risk of death (HR = 0.717) than patients with good prognosis (HR = 1.44). The most significant prognostic factor was KPS ≤80% (35% pts in GC+A 600 vs GC) resulting in HR = 0.50 in favour of GC+A 600. Overall treatment was well tolerated. Most common Grade ≥3 adverse events (AEs) were neutropenia, anemia, thrombocytopenia and hypertension. Frequency of ≥3 Grade toxicities were: 89% (GC), 93% (GC+A 600) and 95% (GC+A 1000). GC+A 1000 had a higher treatment discontinuation rate due to AEs.

    Conclusions

    Advanced BC patients with poor prognosis benefited from apatorsen 600mg combined with first line GC. Apatorsen may be impacting the intrinsic biology of patients with poor risk factors. Further evaluation is warranted in this patient population.

    Session: Oral presentations of the best abstracts

    Location: Saturday, 14 November 2015, 08:50 - 09:30, Auditorium

  • Introduction & Objectives

    The standard of care regarding the timing of chemotherapy (ct) for locally advanced bladder cancer (BC) remains controversial, as only few randomized studies compared adjuvant versus neoadjuvant ct. The level one evidence supports the use of neoadjuvant ct. We compared patients (pts) outcomes following neoadjuvant or adjuvant ct in unselected pts treated in a routine clinical practice.

    Material & Methods

    Data from population based cancer registry of Slovenia was used to select a cohort of 116 pts with locally advanced (M0) bladder cancer (BC) consecutively treated between years 2004 through 2008. Patients with  metastatic disease (M1) were excluded. Among them, 83 pts were treated with perioperative platinum based ct and radical cystectomy, 18 received radiochemotherapy and 15 had an unexplained early termination of treatment. Clinical data and treatment characteristics were retrospectively collected from medical charts.

    Results

    Characteristics  of pts were as follows: median age: 63 years (range 39-78); stage: II and III 43 (37.1 %), IV (M0) 40 (34.5%); histology: Pure transitional cell carcinoma (TCC) 98 (85%), TCC with aberrant differentation 10 (8%), other 7 (6%). Thirty nine of pts (33.6 %) received neoadjuvant and 44 (37.9%) adjuvant ct, most of them cisplatin (cisplatin/gemcitabine or methotrexate/vinblastine/cisplatin) based regimen (adjuvant: 81.8%, neoadjuvant: 90.9%). Median follow-up was 7.4 years. Five-years DFS for the entire group was 59.8%, mOS 4.7 years (95% CI 2.72-6.81). There was no significant difference in DFS  (p=0.68) nor OS (p=0.45) between pts treated with neoadjuvant adjuvant ct.

    Conclusions

    In our analysis there was no statistically significant difference in survival between pts receiving neoadjuvant versus adjuvant systemic platinum-based ct for locally advanced BC.

  • Introduction & Objectives

    Nerve-sparing radical prostatectomy (NS-RP) is widely performed in patients with localized prostate cancer in an effort to retain erectile function and possibly urinary continence after surgery. It remains unclear in which patients NS-RP is oncologically safe and in which patients NS-RP should be performed for optimal functional outcome. Present Dutch guidelines and the guidelines of the EAU do not give clear recommendations on the criteria to perform NS-RP.

    Material & Methods

    Through this study, we wanted to evaluate the considerations and clinical criteria that urologists use to select patients for NS-RP.
    We conducted an online survey, to determine how urologists performing RP make this assessment. Eighty-nine urologists were invited to fill in the questionnaire on NS-RP.
    Questions were subdivided in the following categories: general patient characteristics, clinical prognostic parameters, radiological criteria with a specific focus on multiparametric MRI (mpMRI), pathological prognostic criteria. Furthermore,  patient-related expectations were accounted for.

    Results

    The survey was completed by 72 urologists (80.9% of total), of which 68.1% (49 urologists) perform radical prostatectomy (16.3% open, 18.4% laparoscopic, 73.5% RALP as a first surgeon), and almost all 98.0% (48 urologists) perform NS-RP.
    See table 1 for an overview of the percentage of urologists who use one of the parameters as decision points for NS-RP.

    Table 1. Percentage of urologists that uses one of the parameters as decision points for NS-RP

    Parameter % urologists using parameter to determine side of NS-RP
    Validated sexual function questionnaire pre-operatively (SHIM or IIEF) 55.1%
    Clinical
    -          cT3
    -          Age

    59.2%
    65.3%
    Radiology
    -          mpMRI

    28.1%
    Pathological
    -          Gleason score ≥8
    -          Tumor volume
     
    95.9%
    90.0%
    Shared decision making 93.8%
    Nomograms 59.2%

    Conclusions

    Clear recommendation to perform NS-RP do yet not exist. In our survey, different poor prognostic clinical, radiological, and pathological prognostic parameters had influence on the decision of the urologists to perform NS-RP. As of yet, the decision to NS-RP remains largely one that is taken by the urologist based on his or her own interpretation of a wide set of clinical, radiological, and pathological prognostic parameters.

  • Introduction & Objectives

    Renal cell carcinoma (RCC), which constitutes the majority of malignant renal masses, is a biologically, histologically and clinically heterogeneous disease. Its incidence has been increasing worldwide across all age groups, being twice more frequent in males. Several studies have showed different clinicopathological features according to gender and age, with women and younger patients presenting with smaller, lower stage RCCs. Our objective was to describe the characteristics of treated solid renal masses and to assess whether there were gender and age-specific differences in pathological parameters.

    Material & Methods

    Between January 2010 and February 2015 a total of 467 patients were submitted to nephrectomy at our institution. Baseline demographic and tumour characteristics were collected and compared for identification of differences between gender and age groups (<50, 50-70 and >70 years). Chi-square tests were used for dichotomous variables and t tests for continuous variables.

    Results

    The age of the cohort was 63.5±12.6 years (13.7% <50, 52.7% 50-70, 33.8% >70 years) and 43.4% were female.
    16.3% of the renal masses were benign (11.1% oncocytomas, 3.2% angiomyolipomas, 1.9% other benign conditions) and had smaller dimensions than cancers (Comparisons of the pathological features by gender showed that women had a higher percentage of benign pathology (23.3% vs. 10.9%, p<0.001) and a significantly higher proportion of cromophobe RCCs (27.1% vs. 16.5%), a lower proportion of clear cell RCCs (53.5% vs. 65.7%, p=0.025) and less tumour necrosis (16.2% vs. 29.7%, p=0.003).
    Considering the 3 age groups, younger patients had lower stage tumours (84.0% vs. 77.3% vs. 63.5%, p=0.001) and a higher proportion of cromophobe RCCs (30.0% vs. 21.7% vs. 18.3%, p=0.044). Amongst patients with clear cell RCCs, younger patients had lower stages (81.8% vs. 78.0% vs. 60.9%, p=0.005), lower nuclear grades (78.8% vs. 61.0% vs. 56.3%, p=0.041) and less lymphovascular invasion (9.1% vs. 22.9% vs. 27.6%, p=0.045).

    Conclusions

    Females had more benign lesions and a higher proportion of cromophobe RCCs than males. Younger patients had tumours with lower stages, more cromophobe RCCs and their clear cell RCCs had lower stages, lower nuclear grades and less lymphovascular invasion than those of older patients. These pathologic features have been associated with less aggressive tumours, suggesting an overall better prognosis for both groups.

  • Introduction & Objectives

    Most men diagnosed with prostate cancer in the United States are found to have low-grade tumours. While many of these men are candidates for active surveillance, a proportion may have a bad outcome owing to aggressive prostate cancer that was missed on initial biopsy. A recent prospective study confirmed the 4Kscore® Test accurately predicts the risk of aggressive cancer on prostate biopsy. The purpose of this study was to analyse if the 4Kscore could predict the presence of Gleason ≥7 in a cohort of men with low-grade tumours on prostate biopsy who underwent radical prostatectomy.

    Material & Methods

    A recent large, US multi-center prospective trial enrolled 1312 men referred for prostate biopsy for suspicion of prostate cancer regardless of age, PSA, digital rectal exam findings or prior biopsy status. Prior to TRUS-guided prostate biopsy, blood was collected for a 4Kscore test. The 4Kscore calculates the risk of high-grade (Gleason ≥7) prostate cancer on prostate biopsy by a blood test that measures levels of four kallikrein biomarkers (total PSA, free PSA, intact PSA, and human kallikrein-2) plus age, DRE findings, and prior biopsy status. We used all men who were found to have low-grade (Gleason 6) cancer on biopsy and underwent radical prostatectomy (RP) for this analysis. We assessed the association of the 4Kscore test with the risk of tumour upgrading found in the surgical specimen. Chi squared test was used to evaluate the association.

    Results

    Among the 1312 men enrolled in this trial, 144 men were found to have prostate cancer and underwent radical prostatectomy. Of these men who elected to undergo surgical extirpation, 50 men had Gleason 6 cancer on prostate biopsy, of which the RP pathology revealed 42% (21) men had Gleason ≤6 prostate cancer, 52% (26) men had Gleason 7 prostate cancer, and 4% (2) men had Gleason ≥8 cancer. One patient was found not to have cancer at surgery. Using a 4Kscore cut off of 7.5%, tumour upgrading occurred in significantly more men with a 4Kscore ≥ 7.5% vs. men with a 4Kscore < 7.5% (67% vs. 35%, p=0.034). For a 4Kscore cut off of 20%, tumour upgrading occurred in 85% (11/13) men with a 4Kscore ≥20%, significantly more than tumour upgrading in men with a 4Kscore < 20% (p=0.016).

    Conclusions

    In men who had Gleason 6 disease on biopsy and underwent RP, higher 4Kscores were associated with tumour upgrading at surgery. Men with 4Kscores >20% and Gleason 6 prostate cancer on biopsy have the highest likelihood of harbouring Gleason ≥7 disease and as such these men may not be suitable candidates for active surveillance protocols.

  • Introduction & Objectives

    Abiraterone acetate (AA) is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs survival of metastatic castration-resistant prostate cancer (mCRPC) patients. A low dose of prednisone (P) is given when AA is administered to mCRPC patients. Long-term use of moderate-/high-dose corticosteroids (CS) has an established adverse event (AE) profile. We investigated whether long-term use of low-dose P with or without AA led to CS-associated AEs.

    Material & Methods

    2267 mCRPC patients in COU-AA-301 and COU-AA-302 received 5 mg bid P, representing 2006 patient-years of P exposure. 1333 patients received AA + P. We used an inclusive Standardized MedDRA Queries–oriented approach to identify 112 preferred terms for known CS-associated AEs from both databases. CS-associated AEs during each 3-month exposure interval and across all exposure to P were assessed.

    Results

    The overall incidence of CS-associated AEs for any P exposure was 25%, 26%, and 23% for all patients, AA + P, and P alone, respectively. The incidence of grade ≥ 3 CS-associated AEs with any P exposure was 5%, 5%, and 4% for all patients, AA + P, and P alone, respectively. The most common grade ≥ 3 CS-associated AEs occurring in ≥ 0.1% of all patients were hyperglycemia (2%), cataract (0.4%), diabetes mellitus (0.4%), gastrointestinal hemorrhage (0.3%), adrenal insufficiency (0.1%), hip fracture (0.1%), melena (0.1%), and osteoporotic spinal compression fracture (0.1%). The overall incidence of weight increase (grade 1 and 2 only) was 4%, 4%, and 5% for all patients, AA + P, and P alone, respectively. Most were grade 1 (3.4%). When assessed by duration of exposure (3-month intervals up to ≥ 30 months), grade ≥ 3 CS-associated AEs fluctuated between 1% and 2%, but no discernable trend was observed. The observed change in weight from baseline showed no apparent increase over time.

    Conclusions

    With more than 2000 patient-years of exposure, low-dose P given with or without AA is associated with an overall low incidence of CS-associated AEs. The occurrence of CS-associated AEs remained low with increased duration of exposure to P.

  • Introduction & Objectives

    Decrease in the peripheral blood leukocyte count is a well-known side effect of radiation therapy for prostate cancer and it is considered a negative prognostic factor. Beside the direct toxicity to the bone marrow, a redistribution of circulating leukocytes after pelvic irradiation is also a relevant factor, which is still poorly investigated.

    Material & Methods

    We have set up an animal model to allow tracking of peripheral leukocyte relocation after radiation treatment focused to the urinary bladder. This method will serve to investigate a possible selective accumulation of circulating leucocytes to specific anatomical districts affected by the radiations. Fisher female rats (n=6) were adoptively transferred IV with 4x107 VivoTag-750-labelled syngeneic primary splenocytes, two hours before bladder irradiation. Animals were transurethrally catheterized to allow contrast agent instillation and undergone to a kV cone beam computed tomography (CBCT) imaging to precisely deliver monofraction radiation treatment (15-25 Gy range). Bladder tissue reaction to the radiation was followed over time by ultrasonography, while possible accumulation sites of labelled leukocytes were evaluated by in vivo fluorescent imaging.

    Results

    Preliminary results show that a significant increase in the bladder wall thickness peaked 4 days after radiotreatment in animals treated at a dose of 25 Gy. A fluorescent signal, secondary to labelled splenocytes accumulation, was detectable in the liver and lymph nodes of all adoptively transferred rats, 2 and 6 days after transfer, as expected. A modest specific signal (30% increase) at the bladder level was detected only in animals (n=2) subjected to 25 Gy irradiation (figure 1.a), when compared to the non-irradiated controls (n=3) (figure 1.b). No specific fluorescent signal was detected at the bladder levels in animals treated with 20 and 15 Gy (n=2/group).

    Conclusions

    These data suggest that relocalization to the damaged tissue of peripheral leukocytes can be followed in a non-invasive way and may occur dependently on the radiation dosage. Further analyses are currently ongoing.

  • Introduction & Objectives

    For patients with advanced TCC who have progressed on a platinum-based regimen, no widely accepted standard second line therapy currently exists. A 2-stage phase II study was conducted to assess the activity and toxicity profile of the microtubule inhibitor cabazitaxel (Jevtana; FDA-approved in hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen) in patients with metastatic TCC after failure of prior platinum-based chemotherapy. ClinicalTrials.gov NCT01600339

    Material & Methods

    Patients with one prior platinum based systemic therapy for metastatic TCC received cabazitaxel at a dose of 25 mg\m2 every 21 days with prophylactic GCSF support, until disease progression or unacceptable toxicity. The primary endpoint was objective tumour response rate (ORR). Secondary endpoints included safety, time to progression (TTP), and overall survival (OS).

    Results

    Twenty-three patients were enrolled to the study, 19 of whom received treatment. Male\female ratio was 15\4 and the median age was 67 (range, 56-81) years. Partial response (PR) was observed in 1 patient (5.3%), 10 patients (52.6%) achieved stable disease (SD), including 8 (42.1%) that had prolonged SD (≥16 weeks). Furthermore, the disease control rate (PR or prolonged SD) was 47.4%. At a median follow up of 10.1 months, all patients progressed and 16/19 (84%) died. The median TTP and OS were 4.2 (95% CI, 2.0-6.0) months and 9.9 (95% CI 5.6-13.2) months, respectively. Neutrophil to lymphocyte ratio-NLR ≥3 vs ≤ 3 was associated resistance to treatment: 7/7 progressive disease (P≤0.0023). The median number of treatment cycles was 5 (range 1-10). One patient experienced Grade 5 toxicity. Neutropenic fever occurred in 10.6% of patients. Most common toxicities were anemia and diarrhea.

    Conclusions

    Cabazitaxel had modest efficacy in the treatment of advanced TCC, and there was no evidence of a significant response. Toxicity profile was considerable. The role of Cabazitaxel in urothelial carcinoma may need further evaluation in rational combination strategies, but not as a single agent.

  • Introduction & Objectives

    The phase III trial (Motzer RJ, 2007)that led to the approval of Sunitinib for first line treatment in stage IV renal cell carcinoma, clear-cell type, showed benefit by increasing progression-free survival and response rate. The criteria for patient selection used in clinical trials are defined in order to ensure greater safety and homogeneity of the study population. However, this population may not represent the actual population in clinical practice.
    We applied the inclusion and exclusion criteria of this trial in outpatient population and verified if they resembled the trial population as well as the patient outcomes regarding Progression Free Survival (PFS) and Overall Survival (OS).

    Material & Methods

    We analysed patients that received treatment with Sunitinib at our hospital between January 2011 and June 2015.
    54 patients were older than 18 years, renal cancer clear-cell type, Stage IV, first line treatment. The patients considered ineligible for the clinical trial were those who did not fulfil at least one of the inclusion criteria from the study (measurable disease, performance status 0 or 1, normal hemoglobin, coagulation, hepatic, renal and cardiac function) or who had at least one of the exclusion criteria (brain metastasis, uncontrolled hypertension, cardiovascular events in the previous 12 months). After we analysed treatment duration, reason for stopping treatment and PFS.

    Results

    Of the 54 patients, 47 (87%) would have been considered ineligible for clinical trial. The reasons were in descending order of frequency: Impaired renal function (29 patients) and anemia (29), impaired liver function (11), PS 2 or 3 (8), cerebral metastasis (6), heart failure (4), no measurable disease (4), cardiovascular events in the last 12 months (3) and impaired coagulation (2).
    Regarding the number of criteria not met, 18 patients did not meet 1 criterion, 16 patients did not meet 2 criteria, 11 patients did not meet 3, 2 patients did not meet more than 4 criteria.
    The median time between diagnosis and start of treatment was 7 months. The median duration of treatment was 5 months.
    The reason for discontinuation was progression in 47% (22) cases, toxicity in 15% (7), disease stability in 11% (5) and death in 6%(3).
    PFS was 7.7 months and OS was 21.4 months.

    Conclusions

    The number of patients in clinical practice that would be ineligible for clinical trial is substantial. Most patients failed to meet criteria for participation in the clinical trial population, the most common being renal insufficiency and anemia. Disease progression was the most common cause of Sunitinib discontinuation. Our daily practice patients are different from those selected in clinical trials and may have different outcomes.

  • Introduction & Objectives

    Data on the predictive value (i.e. identifying disease progression) of MRI after previous confirmatory biopsy in men on Active Surveillance (AS) are limited.

    To compare outcomes of MRI + target biopsy (TBx) vs. TRUS-guided systematic biopsy (SBx) at 2nd surveillance biopsy in men on AS and assess whether MRI can selectively identify patients with disease progression (i.e. Gleason score upgrading) to avoid biopsy procedures in those with stable disease.

    Material & Methods

    A total of 30 men on AS received multiparametric MRI in our academic institute at 2nd surveillance biopsy after previous confirmatory biopsy.TBx of suspicious lesions (PI-RADS >= 3) was performed using the MRI-US fusion technique. 62 men (all participants in the PRIAS study; www.prias-project.org)
    who received 2nd surveillance SBx served as a control group. Outcomes of TBx and SBx were compared to assess the upgrading rates and potentially
    saved biopsy procedures when biopsying only those men with a positive MRI. Cox proportional hazard regression analysis was performed to assess whether receiving MRI was an independent predictor for upgrading, after correction for age and PSA.

    Results

      MRI + TBx SBx
    Age (years), median (IQR) 67.5 (62.1 – 72.0) 68.6 (63.5 – 74.3)
    Time between diagnosis and biopsy (years),
    median (IQR)
    3.8 (2.8 – 5.6) 3.9 (2.5 – 4.2)
    PSA at diagnosis (ng/ml), median (IQR) 7.2 (4.8 – 9.3) 4.5 (3.0 – 6.1)
    PSA at biopsy (ng/ml), median (IQR) 10.3 (5.9 – 15.0) 5.2 (3.0 – 8.5)
    Outcome 2nd surveillance biopsy    
    MRI   not suspicious for PCa 8 (27%) /
    No   PCa in biopsy 6 (20%) 24 (39%)
    Gleason   score = 3+3 PCa in biopsy 8 (27%) 33 (53%)
    Gleason   score >= 3+4 PCa in biopsy 8 (27%) 5 (8%)
    Total nr. of patients 30 (100%) 62 (100%)

    MRI+ TBx resulted in more Gleason score upgrading than SBx (27% vs. 8%). However, men who received MRI instead of SBx had higher PSA-levels both at diagnosis and at 2nd surveillance biopsy. After correction for the PSA-levels, receiving MRI was no independent predictor for upgrading: HR = 1.39 (95% CI 0.16 – 3.3), p = 0.672.  Although the PSA-levels and high-grade (Gleason score >= 3+4) PCa rate were higher in the MRI group, 27% of these men had a negative MRI and thus did not receive TBx.

    Conclusions

    A larger sample size and follow-up data are needed to confirm these preliminary results: Performing a MRI at 2nd surveillance biopsy could save app. 30% of prostate biopsy procedures without compromising the identification of disease progression.

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