Darolutamide in Spanish patients with nonmetastatic castration-resistant prostate cancer: ARAMIS subgroup analysis.

Aim: Darolutamide significantly prolonged metastasis-free survival (MFS) versus placebo in the Phase III ARAMIS study. We analyzed outcomes in Spanish participants in ARAMIS. Patients & methods: Patients with high-risk nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus androgen-deprivation therapy. The primary end point was MFS. Descriptive statistics are reported for this post hoc analysis. Results: In Spanish participants, darolutamide (n = 75) prolonged MFS versus placebo (n = 42): hazard ratio 0.345, 95% confidence interval 0.175-0.681. The incidence and type of treatment-emergent adverse events were comparable between treatment arms. Conclusion: For Spanish participants in ARAMIS, efficacy outcomes favored darolutamide versus placebo, with a similar safety profile, consistent with the overall ARAMIS population. Clinical Trials Registration: NCT02200614 (ClinicalTrials.gov).

Darolutamide is an oral treatment for a type of prostate cancer that has stopped responding to other treatments and is at risk of spreading to other parts of the body (termed "nonmetastatic castration-resistant prostate cancer" or "nmCRPC"). In the international ARAMIS study, patients treated with darolutamide lived longer without their cancer spreading than patients who were given placebo (sugar) pills. We wanted to know whether Spanish patients in ARAMIS had similar characteristics and treatment outcomes to other patients in the study. We found that the 75 Spanish patients who were treated with darolutamide had a significantly lower risk of their cancer spreading than the 42 Spanish patients who received placebo. The two groups of Spanish patients had similar side effects.

[Initial experience in microsurgical treatment of varicocele: Comparative analysis with conventional macrosurgical varicocelectomy]. / Experiencia inicial en el tratamiento microquirúrgico del varicocele: análisis comparativo con la varicocelectomía macroquirúrgica convencional.

INTRODUCTION: Varicocele is the most common cause of male infertility and the standard treatment is varicocelectomy. Having recently started performing microsurgical varicocelectomy (MV) in our centre, the objective of this study is to determine the differences in clinical outcomes and laboratory findings between MV and the conventional varicocelectomy (CV). MATERIAL AND METHODS: This is a comparative study between MV and CV in our centre between 01/2013 and 12/2016. We included patients with clinical varicocele and altered seminal parameters. We analyzed the following variables: age, laterality, grade of varicocele, testicular volume, surgical technique used, seminogram parameters prior to and after surgery and recurrence. RESULTS: Between 01/2013 and 12/2016 46 varicocelectomies were performed in our centre, excluding from the study 12 patients due to lack of follow-up. Of the remaining 34, 19 (55.9%) underwent CV and 15 (44.1%) MV. There were no significant differences between the baseline characteristics of both groups. The preoperative sperm count was 30.1±35.6 106/mL for MV vs. 25.6±19.9 106/mL for CV (P=.64) and progressive sperm motility (a+b) was 17.7±13.6% vs. 16.5±10.1% respectively (P=.77). Postoperative sperm count was 29.16±33 106/mL for MV vs. 45.6±55.5 106/mL for CV (P=.32) and progressive motility (a+b) was 26.4±20.1% vs. 27.7±20.4% respectively (P=.85). We observed a tendency towards recurrence in the CV group (26.3%, vs. 6.7% for MV), although not statistically significant (P=.15). CONCLUSIONS: Despite the learning curve with MV, we obtained improvements in seminal analysis similar to those with CV. Even though not statistically significant, there was a tendency to less recurrence in the MV group, consistent with what is already described in medical literature.

Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.

BACKGROUND: Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area. PURPOSE: To investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa. PATIENTS AND METHODS: In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15. RESULTS: The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026). CONCLUSIONS: SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa.

Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression.

BACKGROUND: Besides serum levels of PSA, there is a lack of prostate cancer specific biomarkers. It is need to develop new biological markers associated with the tumor behavior which would be valuable to better individualize treatment. The aim of this study was to elucidate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and prostate cancer progression. METHODS: A total of 494 prostate cancer patients from a Spanish multicenter study were genotyped for 10 SNPs in XRCC1, ERCC2, ERCC1, LIG4, ATM and TP53 genes. The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. Clinical tumor stage, diagnostic PSA serum levels, and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: SNPs rs11615 (ERCC1) and rs17503908 (ATM) appeared as risk factors for prostate cancer aggressiveness. Patients wild homozygous for these SNPs (AA and TT, respectively) were at higher risk for developing cT2b - cT4 (OR = 2.21 (confidence interval (CI) 95% 1.47 - 3.31), p < 0.001) and Gleason scores ≥ 7 (OR = 2.22 (CI 95% 1.38 - 3.57), p < 0.001), respectively. Moreover, those patients wild homozygous for both SNPs had the greatest risk of presenting D'Amico high-risk tumors (OR = 2.57 (CI 95% 1.28 - 5.16)). CONCLUSIONS: Genetic variants at DNA repair genes are associated with prostate cancer progression, and would be taken into account when assessing the malignancy of prostate cancer.

Obesity in percutaneous nephrolithotomy. Is body mass index really important?

OBJECTIVE: To evaluate the influence of obesity in the results of percutaneous nephrolithotomy (PCNL) in terms of efficacy and safety and to evaluate other aspects such as fluoroscopy time, radiation exposure, total operative time, hemoglobin loss, hospital stay, and the need of auxiliary procedures. MATERIALS AND METHODS: We evaluated prospectively all the PCNLs performed at our institution between 2011 and 2012. A series of perioperative and postoperative details were recorded in our database. The patients were distributed in 4 groups using World Health Organization's classification of body mass index (BMI): normal weight, ≤ 25 kg/m(2); overweight, 25-29.9 kg/m(2); obese, 30-39.9 kg/m(2); and morbidly obese, ≥ 40 kg/m(2). Modified Clavien classification was used for reporting the complications. Results were compared between the groups using the chi square and multivariate logistic regression tests. RESULTS: A total of 255 procedures were performed between January 2011 and December 2012. Overall stone clearance was 76.3% and complication rate using the modified Clavien grading system was 31.4%. No statistical differences in terms of complication rate and stone free rate were noted between the 4 groups. Total operative time and radiation doses increase along with BMI. No difference was found in fluoroscopy time, failure to gain access, hospital stay, or need for auxiliary procedures. CONCLUSION: Obesity does not increase complications in PCNL, and the efficacy of the technique is similar to normal weight patients with appropriate expertise. Total operative time and radiation exposure increase along with BMI, putting patients at risk.

Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies.

BACKGROUND: Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics. OBJECTIVE: To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias. DESIGN SETTING AND PARTICIPANTS: A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer. RESULTS AND LIMITATIONS: We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics. CONCLUSION: Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.