EMUC15 - Resource Centre - Search Results

Resource Centre Back to Resource Centre

168 results (Loading...)

Video Filters×
  • organe

  • access

  • procedure

  • pathology

168 Abstracts

  • Introduction & Objectives

    The significance of a detectable PSA (≥0.01ng/ml) at short term after Radical Prostatectomy (RP) for predicting Biochemical Relapse (BCR) is controversial. We compared predictive values of detectable PSA levels within 1 year from RP between patient groups with different degree of Neurovascular Bundle Preservation (NVBP).

    Material & Methods

    From April 2009, men undergoing RP by a single surgeon had NVBP graded at each side from 2 to 0: 2 if NVBP was maximal, 1 if sub-optimal, and 0 if NVB was deliberately severed. NVBP was always attempted except on the side with either a palpable cT3 nodule or a definite extracapsular extension on MRI. For patients up to August 2014, clinicopathologic and follow-up data were collected retrospectively. Exclusion criteria were insufficient data on NVBP, preoperative androgen deprivation therapy, any immediate therapy for adverse pathological result (nodal or seminal vesicle invasion) and PSA nadir not reached. PSA was measured at a regular interval. BCR was defined as PSA of 0.2ng/ml or greater twice consecutively.

    Results

    Among 159 patients identified, 90 had bilateral grade 2 NVBP (group 1) and 69 had anything below that (group 2). Clinicopathologic and follow-up data are summarized in table 1. Positive predictive value (PPV) and negative predictive value (NPV) for predicting BCR at different time points with 0.01ng/ml cutoff PSA were as follow: PPV/NPV for group 1 at nadir, 6 months and 1 year were 15%/91%, 15%/98%, and 11%/97%; PPV/NPV for group 2 at the same points, were 57%/85%, 41/93%, and 32%/92%. All PPVs were significantly higher in group 2 than in group 1 (p<0.05), whereas NPVs were similar between groups.

    Table 1. Clinicopathologic data, PSA and biochemical recurrence
      Group 1 Group 2 p
    No. 90 69  
    PSA, mean (ng/ml) 7.56 10.68 0.025
    cT2 84 43 0.000
    ≥cT3 6 25
    pT2 62 29 0.001
    ≥pT3 28 40
    Pathology Gleason score 6 11 1 0.007
    Pathology Gleason score 7 73 56
    Pathology Gleason score ≥8 6 12
    Surgical margin (+) 50 48 0.072
    Surgical margin (-) 40 21
    PSA nadir >=0.01 ng/ml 33 21 0.411
    PSA nadir5748
    PSA nadir, mean (ng/ml) 0.019 0.027 0.386
    Time to PSA nadir, mean (months) 3.350 3.537 0.566
    PSA at 6 months >=0.01 ng/ml 46 34 0.917
    PSA at 6 months4230
    PSA at 6 months, mean (ng/ml) 0.022 0.039 0.293
    PSA at 1 year >=0.01 ng/ml 45 25 0.234
    PSA at 1 year2925
    PSA at 1 year, mean (ng/ml) 0.031 0.054 0.293
    Biochemical relapse (+) 10 19 0.008
    Biochemical relapse (-) 80 50

    Conclusions

    Our result shows that post-nadir PSA till 1 year following RP remains detectable in the majority of patients with bilateral maximal NVBP, without increasing the risk of BCR. Benign prostatic glandular tissue left in situ during NVBP producing detectable level of PSA is a possible anecdotal explanation.

  • 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

    SBRT-SG 05 (ClinicalTrials.gov Identifier: NCT02192788 ) is a collaborative (SBRT-SG, GICOR and SEOR) phase II trial testing SBRT and hormonotherapy in the oligorrecurrence setting on prostate cancer oligometastic (OPCa) patients. The aim of this study is to determine response, and biochemical control rates, progression free survival, chemotherapy free survival and impact of treatment on quality of life. We describe here the protocol and first results. This type of studies are currently on the rise worldwide representing interest for this kind of approach.

    Material & Methods

    Patients with histologically confirmed prostate cancer (hormone-sensitive or castration-resistant) patients in an oligorrecurrent stage after primary treatment for their disease were assigned to receive SBRT (Vertebral Metastases: 1x16-18Gy or 3x8-9Gy. Lymph node Metastases: 3x10-11 Gy or 6x7,5Gy. Non-spinal bone metastases: 1x16Gy or 3x10Gy). Medical treatment  could include LHRH analogues, antiandrogens, zoledronic acid or denosumab. The following Inclusion Criteria were established: Time to biochemical recurrence more than 1 year; PSA doubling time> 2 months; Less than 5 bone or lymph node metastases (including spinal) by Choline PET-CT or / and WB-DWI-MRI. To ensure homogeneity in the sample, all patients should have hormone therapy according to current recommendations planning its withdrawal within two years after treatment if biochemical control has been achieved. The percentage of castration resistance patients will be at most 30% and at least 10%of the sample. Concomitant treatment with chemotherapy, abiraterone or enzalutamide is not allowed.

    Results

    At present, 36 patients have been recruited in 9 centers, with 43 locations of oligometastases treated.  2 have been evaluated at 1 year, 6 at  9 months,  9 at  6 months, 8 at 3 months, and 11 are pending to the initial studies. In all there is local and biochemical control. No patient had symptoms related to local progression of the disease. One of them has presented distant disease during follow-up at 6 months. All of them have not grade ≤ 2 toxicity  related to SBRT. 2 patients were included in a state of castration resistance without the need to start hormonal treatment of second generation.

    Conclusions

    This trial presents a favorable pace of recruitment with good initial figures of biochemical control and local control without the appearance of remarkable SBRT related toxicity at this time.

  • 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

    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

×