The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.

Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature.

Background: Abiraterone acetate and enzalutamide are standard treatments for chemotherapy-naive metastatic castration-resistant prostate cancer (CN-mCRPC). The purpose of this study was to evaluate the effectiveness and safety of these medications in elderly (>= 75 years old) compared with young CN-mCRPC patients in a real-world clinical setting. Secondarily, we explored the survival prognostic value of different anatomo-clinical factors in elderly group. Methods: In this retrospective observational multicentre study, we included 134 consecutive CN-mCRPC patients, 64 young and 70 elderly men, who had received AA or Enz. Results: We did not find significant differences in treatment duration [16.6 months, (95% CI 9-24.2 months) vs. 16.8 months (95% CI: 6.3-27.2 months); p = 0.926] and overall survival [median not reached vs. 23.3 months (95% CI 10.2-36.3 months); p = 0.131] between the young and elderly groups. In elderly group, the only predictors of overall survival with AA or Enz were good ECOG performance status and high G8 score. Adverse events of grade >= 3 was similar in elderly group (12.9%) and in the young group (15.6%). Treatment was discontinued due to AEs in 6.3% of young group and 18.6% of elderly group. Conclusions: Effectiveness and safety of treatment of CN-mRCPC with Abiraterone acetate and enzalutamide were similar in older and younger patients, although treatment discontinuation due to AEs was more frequent in the older age group. In addition to ECOG PS, assessment using specific geriatric scales as G8 screening tool could help to identify patients aged >= 75 who would most benefit from treatment with new-generation hormone therapy.

588 Background: SNPs predictive of survival outcomes in patients (pts) with localized and metastatic RCC have been identified previously by us [Garrigós C et al, 2017]. Fifteen SNPs in 9 genes involved in angiogenesis and metabolism of antiangiogenics were recognized as predictive/prognostic in a cohort of 102 pts. The aim of the present study is to validate these associations in an independent cohort of RCC pts Methods: Genotyping was performed in DNA isolated from paraffin-embedded tumor samples from 87 pts with localized and metastatic RCC. DNA was extracted by a commercial kit (QiAGEN) and amplified with a specific primers pool for each SNP as determined by the manufacturer (Lifetech). The 15 SNPs were individually genotyped by Real time quantitative PCR with specific primers and Taqman probes (Lifetech). The presence of the selected SNPs was correlated with clinical features such as disease free survival (DFS), progression free survival (PFS) and overall survival (OS). SPSS v24 was used for statistical analysis. Results: In the localized pts (n = 66), Fuhrman grades 3-4 and stage T3-T4 significantly associated with DFS (p = 0.025 and p = 0.004, respectively). The presence of allele C of rs307826 (FLT4 gene) correlated with a greater chance of relapse (p = 0.025) and also with a shorter DFS (21 vs 35 months, p = 0.007). For the metastatic pts (n = 21), allele C of rs307826 (FLT4 gene) and allele A of rs9800958 (PRKAR1B) were linked with a shorter PFS [(8 vs 18 months, p = 0.036) and (8 vs 17 months, p = 0.043) respectively]. In the localized cohort, allele T of rs2227543 (IL8 gene) was associated with longer OS (14 vs 3 months, p = 0.039) while allele G of rs10013228 (KDR gene) linked with worse OS (4 vs 17 months, p = 0.063). Conclusions: This analysis comes to confirm our previous observations that certain genotypes could be used as prognostic/predictive factors in RCC. This is particularly important in an era where multiple treatment options are available for this disease.

Despite major advances in the knowledge of the molecular basis of renal cell carcinoma, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. With these premises, we aimed to analyse the expression and to determine the prognostic and predictive value of 64 key single nucleotide polymorphisms in 18 genes related with angiogenesis or metabolism of antiangiogenics in two cohorts of patients with localized and advanced renal cell cancer treated at our institution. The presence of the selected single nucleotide polymorphisms was correlated with clinical features, disease free survival, overall survival and response rate. In patients with localized renal cell cancer, 5 of these polymorphisms in 3 genes involved in angiogenesis predicted for worse disease free survival (VEGFR2: rs10013228; PDGFRA: rs2228230) or shorter overall survival (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p < 0.05). Rs2071559 in VEGFR2 showed a protective effect (p = 0.01). In the advanced setting, 5 SNPs determined inferior overall survival (IL8: rs2227543, PRKAR1B: rs9800958, PDGFRB: rs2302273; p = 0.05) or worse response rate (VEGFA: rs699947, rs3025010 p ≤ 0.01)). Additionally 1 single nucleotide polymorphism in VEGFB predicted for better response rate rs594942 (p = 0.03). Genetic analysis of renal cell carcinoma patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics drugs seem to determine post-surgical outcomes and treatment response in our series.

437 Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in patients (pts) with both localized and advanced RCC treated at Hospital Universitario Virgen del Rocío. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). 64 SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview, and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS), and response to treatment (RR). SPSS v16 was utilized for statistical analyses. Results: In pts with localized RCC, 6 SNPs in 3 genes involved in angiogenesis predicted for worse DFS (VEGFR2: rs10013228, rs2071559; PDGFRA: rs2228230) and shorter OS (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p<0.05). In the advanced setting, 7 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics determined inferior OS (IL8: rs2227543, NR1l2: rs3814055, NR1l3: rs2307424, PDGFA: rs9800958, PDGFRB: rs2302273) and worse RR (VEGFA: rs699947, rs3025010 p<0.01)). Additionally 3 SNPs in PDGFR-B and VEGF isoforms predicted for better RR (PDGFRB: rs17708574 (p=0.08), VEGFB: rs594942 (p=0.03), VEGFC: rs2016110 (p=0.07). Conclusions: Genetic analysis of RCC patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics seem to determine post-surgical outcomes and treatment response in our series. These results are promising. Validation of the results is ongoing.

470 Background: MiRNAs play an important role as modulators of gene expression in a multitude of biological processes, being closely linked to the regulation of development and cell differentiation. Promising results about their value as predictors of drug response have been published in lung, colorectal cancer [Molina-Pinelo] and RCC [García-Donas]. This study aims to determine whether miRNAs can predict TKIs “extreme responses” in mRCC pts. Methods: RNA from formalin fixed paraffin embedded tumor and non-tumor samples from 15 pts with mRCC was extracted with mirVana miRNA isolation kit (Ambion). We defined as TKI “extreme responders” those pts that either had a long-term response (LR) (PFS˃11 months, n=7) or that were primary refractory (PR) (progression as best response, n=8). The expression of 754 miRNAs was analyzed with TaqMan Low Density Array Human MicroRNA Panel (TLDA) (ThermoFisher). QPCR was carried out in the System of Gene Expression and Genotyping Arrays module ViiA7. A qPCR ThermoFisher software specifically designed was used to calculate the ΔCt, cluster analysis, comparison between groups and primary analysis of the results. MiRNAs differentially expressed were analyzed independently by individual qPCR assays in the same cohort. A validation in an external cohort is being currently conducted. Results: Four miRNAs were significantly associated with patient response and differentially expressed in PR vs. LR (up-regulated in PR: miR-425-5p, down-regulated in PR: miR-139-3p, let-7d, and let-7e). Validation in our cohort was successful with let-7d and let-7e (p<0.05). Regarding differential expression in tumor vs non-tumor samples 14 miRNAs were identified by TLDA. Seven of those were validated in our series (tumor up-regulated: miR-146b, miR-21, miR-155, miR-122; tumor down-regulated: miR135a, miR-200c, miR-187) (p<0.05). These miRNAs were located in genes related with apoptosis, proliferation, metastasis, migration, and oncogenic pathways. Conclusions: MiRNAs could represent a valid predictive biomarker in mRCC treatment. These results need further validation in an independent cohort [work in progress].

Cite this article: Robles C, Conde M, Benedetti J, Medina R, Sancho P, et al. (2017) Desperation Surgery as a Successful Approach in Chemorefractory Testicular Germ Cell Cancer: The Relevance of a Multidisciplinary Approach. JSM Clin Oncol Res 5(1): 1054. *Corresponding author Ignacio Duran, Department of Medical Oncology, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013 Seville, Spain, E-mail:

e16074 Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined mostly using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in two cohorts of RCC patients (pts) [localized and advanced] RCC treated at our institution. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). Sixty-four SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). Statistically significant SNPs were validated in an external cohort by individual assays. The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS) and response to treatment (RR). SPSS v20 was utilized for statistical analyses. Results: In pts with localized RCC, 2 SNPs in 2 genes involved in angiogenesis showed a protective effect (VEGFR2: rs2071559, PDGFRA: rs4358459) and others SNPs predicted for worse DFS (VEGFR2: rs10013228, rs1870377, PDGFRA: rs2228230) and shorter OS (VEGFR2: rs2305948, rs10013228; VEGFR3: rs6877011, rs307826) (p < 0.05). In the advanced setting, 6 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics were statistically implicated in OS (IL8: rs2227543, PDGFA: rs9800958, PDGFRB: rs2302273 (p≤0.05)) and RR (VEGFA: rs699947, rs3025010, VEGFB: rs594942 (p < 0.03)). These 14 SNPs are currently being validated in an external cohort of 80 patients with RCC and this data will be presented. Conclusions: These SNPs in genes critical to angiogenesis and metabolism of antiangiogenics might be used as potential prognostic/predictive biomarkers. Prospective validation is ongoing.

Penile incarceration by foreign objects for sexual stimulation purposes is a situation described in universal literature, however it is a rare situation that the urologist must face in the emergency room. A 75-year-old male is presented to whom his sexual partner had placed a ring in the coronal sulcus.

Vascular complications represent a significant cause of morbidity and mortality following a kidney transplant. Pseudoaneurysms are rare, occurring in approximately 1% of cases. We present a 15-yr-old patient who received a kidney transplant in the right iliac fossa. Thirty-six days following the transplant, the patient was admitted to the hospital because of a marked increase in serum creatinine levels, arterial hypertension, scrotal edema, and lower right limb pain. The patient did not present fever or raised inflammatory markers. A pseudoaneurysm was diagnosed by means of a Doppler echography and a CT. By a selective arteriography of the right iliac artery, we placed a 8 x 5 cm stent to isolate the pseudoaneurysm, due to the high risk of an extensive defect occurring in the arterial wall. Forty-eight h later the patient underwent transplant nephrectomy. Seven days following surgery, the patient experienced febrile syndrome and therefore another CT was carried out which showed a large abscess around the stent. So we decided to perform another intervention in order to drain this abscess. Due to the extensive loss of the arterial wall where the prosthesis was largely exposed, we ligated the common iliac and external iliac arteries, removed the prosthesis and performed a femoro-femoral bypass with the usual subcutaneous positioning of the prosthesis (separate from surgical site). The stent and mural thrombus were sent for culture analysis and Candida albicans was observed. The diagnosis of a pseudoaneurysm in these types of patients continues to be considered as a surgical emergency by the majority of authors. Transplantectomy is the most frequently used treatment technique. Positioning a stent prior to transplantectomy avoids ligature of the iliac artery in the majority of cases.