Arie Carneiro

Clinical Use of Expanded Prostate Cancer Index Composite for Clinical Practice to Assess Patient Reported Prostate Cancer Quality of Life Following Robot-Assisted Radical Prostatectomy

Purpose: EPIC‐CP (Expanded Prostate Cancer Index Composite for Clinical Practice) is a short questionnaire that comprehensively measures patient reported health related quality of life at the point of care. We evaluated the feasibility of using EPIC‐CP in the routine clinical care of patients with prostate cancer without research infrastructure. We compared longitudinal patient and practitioner reported prostate cancer outcomes. Materials and Methods: We reviewed health related quality of life outcomes in 482 patients who underwent radical prostatectomy at our institution from 2010 to 2014. EPIC‐CP was administered and interpreted in routine clinical practice without research personnel. We compared practitioner documented rates of incontinence pad use and functional erections to patient reported rates using EPIC‐CP. Results: A total of 708 EPIC‐CP questionnaires were completed. Mean urinary incontinence domain scores were significantly higher (worse) than baseline (mean ± SD 0.6 ± 0.2) 3 and 6 months after treatment (mean 3.1 ± 2.3 and 2.2 ± 2.1, respectively, each p <0.05) but they returned to baseline at 12 months (mean 1.6 ± 1.7, p >0.05). Mean sexual domain scores were significantly worse than baseline (mean 2.4 ± 2.8) at all posttreatment time points (each p <0.05). Practitioners significantly overestimated incontinence pad‐free rates at 3 months (48% vs 39%) and functional erection rates at 3 months (18% vs 12%), 6 months (38% vs 23%) and 12 months (45% vs 23%, each p <0.05). Conclusions: EPIC‐CP is feasible to use in the routine clinical care of patients with prostate cancer without requiring a research infrastructure. Using EPIC‐CP in clinical practice may help practitioners objectively assess and appropriately manage posttreatment side effects in patients with prostate cancer.

Effect of Prior Focal Therapy on Perioperative, Oncologic and Functional Outcomes of Salvage Robotic Assisted Radical Prostatectomy

Purpose: We assessed the impact of focal therapy on perioperative, oncologic and functional outcomes in men who underwent salvage robotic assisted radical prostatectomy compared to primary robotic assisted radical prostatectomy. Materials and Methods: Focal therapy was performed in patients presenting with Gleason score 3 + 3 or 3 + 4, clinical stage cT2a or less, serum prostate specific antigen 15 ng/ml or less, unilateral positive biopsy, maximum length of any positive core less than 10 mm and life expectancy greater than 10 years. Focal therapy was defined as target ablation of the index lesion plus a 1 cm safety margin in the normal ipsilateral prostatic parenchyma. The salvage group included 22 men who underwent salvage prostatectomy after focal therapy failure. The primary group was defined using matched pair 1:2 selection of 44 of 2,750 patients treated with primary prostatectomy. The primary and secondary end points were the between group differences in functional and oncologic outcomes, respectively. Results: Complication rates were comparable (p >0.05). Pad‐free probability was comparable between the groups at 1 and 2 years (p = 0.8). Recovery of erectile function was significantly lower after salvage robotic assisted radical prostatectomy (p = 0.008), which also showed a significantly lower probability of cumulative biochemical recurrence‐free survival compared to primary robotic assisted radical prostatectomy (56.3% vs 92.4% at 2 years, p = 0.001). Salvage prostatectomy demonstrated a significantly increased risk of biochemical recurrence (HR 4.8, 95% CI 1.67–13.76, p = 0.004). Study limitations included the retrospective nature, the lack of randomization and the short followup. Conclusions: Salvage robotic assisted radical prostatectomy after focal therapy failure is feasible with acceptable complication rates. However, patients assigned to primary focal therapy should be advised about a poorer prognosis in terms of oncologic control and lower erectile recovery rates in case of a future salvage surgery.

Clinical utility of transperineal template-guided mapping biopsy of the prostate after negative magnetic resonance imaging−guided transrectal biopsy

PURPOSE We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)-guided biopsy. MATERIALS AND METHODS Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI-guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection. RESULTS The mean age was 61.6 ± 6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients. CONCLUSION Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI-guided biopsy. Most of the cancers detected were predominantly anterior tumors.

Image-guided percutaneous renal cryoablation: Five years experience, results and follow-up

OBJECTIVES To describe the experience of our institution in image-guided renal nodules percutaneous cryoablation, evaluating demographic and technical aspects as well as efficacy, safety and follow up. MATERIALS AND METHODS Retrospective study approved by our institutional review board. Seventy-one renal tumors evaluated in 60 patients treated with image guided percutaneous renal cryoablation from January 2009 to December 2015. No patient was excluded from study, even those who were lost on follow up. All the procedures were guided both by ultrasound and tomography. An argon and helium based cryoablation machine was used for all treatments. Hydrodissection was performed when the bowel or ureters were within 1 cm (iodinated contrast media in dextrose solution). Complications were assessed by the terminology criteria of the National Institutes of Health (NIH). Patients were monitored and evaluated by ultrasound, tomography, MRI and/or PET-CT. RESULTS In most procedures (91.9%) only one nodule was treated. Nodules had a median size of 1.6 cm. Most nodules (61,9%) were exophytic. Hydrodissection and retrograde warm pyeloperfusion were performed in most procedures. Among all variables evaluated in univariate analysis, nearness of nodule to collecting system and anterior/posterior location were significantly associated with PRCA complications. No other factor evaluated was significantly associated with complications. CONCLUSION PRCA is solid alternative to traditional surgical therapies for treatment of small renal tumors in wide subset of patients. Medium term evidence shows excellent long-term oncological results, similar to nephrectomy, with minimal risk of major complications.

Are localized prostate cancer biomarkers useful in the clinical practice

Prostate cancer presents itself in a heterogeneous way with both aggressive and indolent forms. Despite the controversy surrounding its use, prostate-specific antigen screening ultimately leads to a greater number of diagnosed patients. One of the biggest challenges in clinical practice is to select the right patients for biopsy and, among diagnosed patients, to differentiate tumors with an indolent course from those with an unfavorable prognosis, in order to determine the best therapeutic decision for each case, avoiding unnecessary interventions. Currently, several types of biomarkers are available for clinical use in patients with prostate cancer, which include blood-based (prostate-specific antigen, Prostate Health Index®, 4K score®); urine sample-based (PCA3, SelectMDx®, ExoDx Prostate IntelliScore®); and biopsy, transurethral resection, or radical prostatectomy tissue-based (ConfirmMDx®, Oncotype®, Prolaris®, Decipher®). The aim of this review is to provide an overview of the current state of evidence and to highlight recent advances in the evaluation and diagnosis of prostate cancer, with emphasis on biomarkers related to diagnosis and to prognostic evaluation of localized prostate cancer.

The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature

Background: Prostate cancer (PCa) is a heterogeneous disease that lends itself toward numerous therapeutic options depending on its risk stratification. One of the greatest challenges in PCa urologic practice is to select patients who should be referred for biopsy and, for those patients who are diagnosed with cancer, to differentiate between patients with indolent disease from those with an unfavorable prognosis and, to determine ideal patient management and avoid unnecessary interventions. Accordingly, there is a growing body of literature reporting immunohistochemical studies with the objective of determining a prostate cancer prognosis. Among the most frequent biomarkers studied are Ki-67, p53, PTEN, MYC, and ERG. Based on these findings, we systematically reviewed articles that assessed the role of these main prognostic markers in prostate cancer. Methods: Consistent with PRISMA guidelines, we performed a systematic literature search throughout the Web of Science and PubMed Medline databases. We considered all types of studies evaluating the role of Ki-67, p53, PTEN, MYC, and ERG immunohistochemical analysis in prostate cancer until July 2017. Results: We identified 361 articles, 44 of which were summarized in this review. Diagnostically, no single immunohistochemical marker was able to define a tumor as benign or malignant. Prognostically, Ki-67, p53, and MYC were related to the tumor grade given by Gleason score and to the tumor stage (higher levels related to higher tumor grade). Furthermore, Ki-67 was also related to higher PSA levels, shorter disease-free intervals and shorter tumor-specific survival; the latter was also related to p53. The loss of PTEN protein expression showed a higher association with biochemical recurrence and with a worse prognosis, beyond that predicted by the Gleason score and tumor stage. ERG staining also showed a strong association with biochemical recurrence. Conclusion: There are several studies relating immunohistochemical markers with clinical-laboratorial outcomes in prostate cancer, the most frequent being Ki-67, p53, ERG, PTEN, and MYC. However, none of these markers have been validated by literary consensus to be routinely applied in medical practice.

Focal Therapy for Prostate Cancer: A More Vehement View of the Approach Could Translate into Real Benefits for Our Patients

The literature on focal therapy is currently insufficient to recommend it as first-line treatment. We need information from both randomised controlled trials and prospective registries for every available energy. That said, important research is under way in this field, and the door should be kept open to an approach that has the potential to offer adequate cancer control with lower morbidity and better post-treatment quality of life in properly selected patients.

Genitourinary and gastrointestinal toxicity among patients with localized prostate cancer treated with conventional versus moderately hypofractionated radiation therapy: systematic review and meta-analysis

Abstract Background: Hypofractionated (HRT) prostate radiation therapy has the potential to deliver a higher biologically effective dose over a shorter time compared with conventional fractionation (CRT). HRT, giving fewer fractions each with higher dose, might improve the therapeutic ratio, resource use and patient convenience but the toxicity is still controversial. Our objective was to compare the gastroinstestinal (GI) and genitourinary (GU) toxicity of HRT versus CRT. Methods: Systematic review and meta-analysis of randomized clinical trials studies in PubMed, Cochrane and EMBASE databases published through December 2016 was done. Only randomized trials that evaluated patients with localized prostate cancer (PCa) undergoing CRT or HRT were included. In these studies, the daily dose was 1.8 Gy or 2 Gy per day for CRT and 2.4 to 3.4 Gy for HRT. Results: 7317 patients in nine studies were analyzed. Six studies included acute GU toxicity data which showed similar rates for both HRT and CRT (32.6vs. 31.9%; RD 0.00; 95% CI; −0.03,0.03; p = .81; I2 = 0%). Similarly, seven studies showed no difference in late GU toxicity based on treatment schedule (28.7 vs. 28.0%; RD −0.01; 95% CI; −0.04,0.03; p = .67; I2 = 52%). GI toxicity at three months after radiotherapy was higher in patients treated with HRT in six studies (27.5 vs. 21.9%; RD 0.06; 95% CI; 0.02,0.10; p = .004; I2 = 39%); however, eight studies showed GI toxicity 12 months or more after radiotherapy that was statistically the same (12.9 HRT vs. 16.2% CRT; RD −0.01; 95% CI; −0.04,0.02; p = .41; I2 = 58%). Conclusion: In meta-analysis of the available randomized trials on moderate HRT versus CRT for prostate cancer, acute and late GU toxicity were similar for both treatment schemes. While HRT was associated with higher acute GI toxicity, late toxicity was similar.

Adult UrologyOncology: Prostate/Testis/Penis/UrethraClinical Use of Expanded Prostate Cancer Index Composite for Clinical Practice to Assess Patient Reported Prostate Cancer Quality of Life Following Robot-Assisted Radical Prostatectomy

Purpose: EPIC‐CP (Expanded Prostate Cancer Index Composite for Clinical Practice) is a short questionnaire that comprehensively measures patient reported health related quality of life at the point of care. We evaluated the feasibility of using EPIC‐CP in the routine clinical care of patients with prostate cancer without research infrastructure. We compared longitudinal patient and practitioner reported prostate cancer outcomes. Materials and Methods: We reviewed health related quality of life outcomes in 482 patients who underwent radical prostatectomy at our institution from 2010 to 2014. EPIC‐CP was administered and interpreted in routine clinical practice without research personnel. We compared practitioner documented rates of incontinence pad use and functional erections to patient reported rates using EPIC‐CP. Results: A total of 708 EPIC‐CP questionnaires were completed. Mean urinary incontinence domain scores were significantly higher (worse) than baseline (mean ± SD 0.6 ± 0.2) 3 and 6 months after treatment (mean 3.1 ± 2.3 and 2.2 ± 2.1, respectively, each p <0.05) but they returned to baseline at 12 months (mean 1.6 ± 1.7, p >0.05). Mean sexual domain scores were significantly worse than baseline (mean 2.4 ± 2.8) at all posttreatment time points (each p <0.05). Practitioners significantly overestimated incontinence pad‐free rates at 3 months (48% vs 39%) and functional erection rates at 3 months (18% vs 12%), 6 months (38% vs 23%) and 12 months (45% vs 23%, each p <0.05). Conclusions: EPIC‐CP is feasible to use in the routine clinical care of patients with prostate cancer without requiring a research infrastructure. Using EPIC‐CP in clinical practice may help practitioners objectively assess and appropriately manage posttreatment side effects in patients with prostate cancer.

PD61-04 COMPARISON OF GLEASON UPGRADING RATES IN TRANSRECTAL ULTRASOUND SYSTEMATIC RANDOM BIOPSIES VERSUS US-MRI FUSION BIOPSIES FOR PROSTATE CANCER.

INTRODUCTION AND OBJECTIVES: With current standard cross-sectional imaging (CT or MRI) detection of prostate cancer lesions in patients with biochemical recurrence (BCR) after radical prostatectomy remains challenging, especially at low PSA values. Recently, 68Ga-PSMA PET imaging has been shown to improve detection rates. However, up to now published case series include only a limited number of patients at low PSA values. METHODS: For this retrospective analysis 272 pts with BCR after radical prostatectomy were extracted from the institutional database who presented with a PSA value from 0.2 up to 1ng/ml at the time of 68Ga-PSMA PET/CT imaging. 68Ga-PSMA PET/CT was evaluated by one experienced reader for lesions suggestive for prostate cancer recurrence and site of suspicious lesions was reported. Patients were grouped according to PSA value, from 0.2 e 0.5ng/mL and from >0.5 e 1.0ng/mL. Primary T-, N-stage, GleasonScore, D’Amico-Classification, previous local radiation therapy as well as concurrent androgen deprivation therapy (ADT) was correlated to detection rates. RESULTS: In total, in 54.5 % (73/134) of patients with PSA from 0.2 e 0.5ng/mL and in 76.1% (102/134) of patients with PSA >0.5 e 1.0ng/mL suspicious findings on 68Ga-PSMA PET/CT imaging were noted. Sites of recurrence were local (37.0% and 41.2%), pelvic or retroperitoneal lymph nodes (45.2% and 54.9%), bone (24.7% and 29.4%), supradiaphragmal lymph nodes (6.8% and 6.9%) as well as others (4.1% and 2.0%). In patients with primary locally advanced tumors (pT>3a), primary N+ disease, Gleason-Scores >8, primary higher D’Amico-Classification, previous radiation therapy as well as with concurrent ADT positive findings on 68Ga-PSMA PET/ CT were more likely compared to patients without these characteristics. CONCLUSIONS: 68Ga-PSMA PET/CT is able to identify sites of recurrent prostate cancer after radical prostatectomy even at low PSA values up to 1ng/ml in a significant number of patients e especially in patients with primary more aggressive tumor characteristics, previous local radiation therapy or concurrent ADT e and thus will very likely present the future imaging technique in these patients. As salvage therapies (local radiation therapy, salvage lymph node dissection or PSMA-radioguided surgery) are most effective at low PSA-levels, early detection of cancerous foci by 68Ga-PSMA PET might even improve oncological results.