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PURPOSE To generate and present survey results on important issues relevant to treatment and follow-up of localized and locally advanced, high-risk prostate cancer (PCa) focusing on developing countries. METHODS A panel of 99 PCa experts developed more than 300 survey questions of which 67 questions concern the main areas of interest of this article: treatment and follow-up of localized and locally advanced, high-risk PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up of localized and locally advanced, high-risk PCa in areas of limited resources discussed in this article. RESULTS The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion and not on a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations considered cost-effectiveness as well as the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. Results were tabulated in real time. CONCLUSION The voting results and recommendations presented in this article can guide physicians managing localized and locally advanced, high-risk PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment of localized and locally advanced, high-risk PCa in developing countries have not been defined, this article will serve as a point of reference when confronted with this disease.

Introduction and objective: Penile cancer is a rare disease that has high morbidity and mortality rates. While a few biomarkers related to prognosis have been previously described to date none of them was adopted in clinical practice. Our aim was to identify a molecular signature based on miRNA expression levels that could identify those patients with high risk of metastatic penile carcinoma. Methods: We prospectively collected fresh samples of primary tumors from 11 patients with squamous cell penile carcinoma who underwent surgical treatment between July/2015 and June/2017. Five patients had localized disease (non-metastatic group) and 6 had inguinal lymph node metastases (metastatic group). RNA was purified and microarray analysis was performed using miRNA 4.0 Genechip (Affymetrix). We identified differentially expressed miRNAs (DEmiRs) comparing metastatic in relation to non-metastatic groups using TAC Software (Affymetrix), fold change (FC) > 1.5 and p Results: Twenty two DEmiRs (17 up- and 5 downregulated) were identified when comparing metastatic in relation to non-metastatic patients. Hierarchical clustering analysis showed a set of 7 DEmiRs (miR-181c-5p, 744-5p, 196b-5p, 200a-5p, 152-3p, 421, 149-5p) which clustered samples according to prognosis. Network interaction analyses identified transcriptional factors (NANOG, Oct-3/4, SOX2 and c-Jun) that commonly regulate those DEmiRs. Moreover, TGFB, CMYC, RICTOR, ADAM-17 and PTEN are some of the common targets of those DEmiRs and are more likely to be deregulated. Validated and predicted targets of these 7 DEmiRs were found enriched in relevant pathways such as “Proteoglycans in cancer”, “Pathways in cancer”, “miRNAs in cancer” and “Signaling pathways regulating pluripotency of stem cells”. Among their targets, CMYC, SP1, ESR1 and AR are examples of hubs which presented the highest number of network interactions. Conclusions: We found 7 DEmiRs correlated with prognosis and capable of discriminating metastatic from non-metastatic tumors. In addition, their targets are enriched in cancer-related pathways and could be potential biomarkers for prognosis in penile cancer. Citation Format: Tatiane K. Furuya, Claudio B. Murta, José Pontes Jr, Miyuki Uno, Alexis Carrasco, Laura C. Sichero, Luisa L. Villa, Rafael F. Coelho, Giuliano B. Guglielmetti, Mauricio D. Cordeiro, Kátia R. Leite, Miguel Srougi, Roger Chammas, William C. Nahas. Correlation of a microRNA expression profile and the prognosis of penile cancer: A prospective study using microarray data analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5399.

Objectives. To evaluate the correlation between race and lymph node metastasis for prostate cancer by analyzing which preoperative parameters may predict lymph node status in both races. Methods. We analyzed a group of patients (552 American white men [AWM] and 423 African-American men [AAM]) who underwent radical prostatectomy plus modified pelvic lymphadenectomy between January 1991 and June 1997. Patients who received neoadjuvant radiation or hormone therapy were excluded. Univariate and multivariate analyses were performed to determine the influence of race on lymph node positivity, as well as to correlate the preoperative parameters (serum prostate-specific antigen [PSA], biopsy Gleason score, and clinical stage) with lymph node metastasis for each race separately. Results. The AAM presented with significantly higher preoperative Gleason scores and PSA levels than AWM. However, comparing lymph node status by race, the difference of positivity (41 AWM [7.4%] and 22 AAM [5.2%]) was not statistically significant ( P = 0.16). The percentage of positive nodes was similar in both races for each subset of PSA, Gleason score, and clinical stage. Despite the statistical significance of the three preoperative parameters in univariate analysis, in multivariate analysis only PSA and Gleason score were independent predictors of positive lymph nodes. Conclusions. There is no influence of race on lymph node metastasis, despite AAM presenting with higher preoperative Gleason scores and PSA levels. In multivariate analysis, preoperative Gleason score and PSA were independent factors for positive nodes regardless of race.

Accurate preoperative and postoperative risk assessment has been critical for counseling patients regarding radical prostatectomy for clinically localized prostate cancer. In addition to other treatment modalities, neoadjuvant or adjuvant therapies have been considered. The growing literature suggested that the experience of the surgeon may affect the risk of prostate cancer recurrence. The purpose of this study was to develop and internally validate nomograms to predict the probability of recurrence, both preoperatively and postoperatively, with adjustment for standard parameters plus surgeon experience.The study cohort included 7,724 eligible prostate cancer patients treated with radical prostatectomy by 1 of 72 surgeons. For each patient, surgeon experience was coded as the total number of cases conducted by the surgeon before the patient's operation. Multivariable Cox proportional hazards regression models were developed to predict recurrence. Discrimination and calibration of the models was assessed following bootstrapping methods, and the models were presented as nomograms.In this combined series, the 10-year probability of recurrence was 23.9%. The nomograms were quite discriminating (preoperative concordance index, 0.767; postoperative concordance index, 0.812). Calibration appeared to be very good for each. Surgeon experience seemed to have a quite modest effect, especially postoperatively.Nomograms have been developed that consider the surgeon's experience as a predictor. The tools appeared to predict reasonably well but were somewhat little improved with the addition of surgeon experience as a predictor variable.

Purpose Loss of heterozygosity (LOH) at 16q23.2 is an early and frequent event in prostate cancer. LOH is thought to be involved in tumor development and progression mainly through inactivation of tumor suppressor genes. However, it has been demonstrated that LOH at 16q23.2 is an independent marker of good prognosis in breast cancer. In the present study, we evaluated the clinical relevance of 16q23.2 LOH in prostate cancer, together with other LOH frequently associated with this disease. Experimental Design Tumoral and normal DNA were extracted from 61 radical prostatectomies, including 30 pT2 tumors with low Gleason score 5,6 (group 1), and 31 pT3 high grade (G8–9) tumors (group 2). Median follow-up after surgery was 42 months. Three patients reccured in group 1, and 20 in group 2. LOH analysis was performed using highly informative microsatellites markers, at 16q23.2, and at other chromosome loci frequently deleted in prostate cancer: 7q31, 8p22, 12p13, 13q14, and 18q21. Results LOH at 16q23.2 is associated with low stage low grade tumors and lower preoperative PSA, while LOH at 8p22 is more frequent in high stage high grade prostate cancer. In group 2, 16q23.2 LOH was the only predictor of disease-free survival in univariate and multivariate analysis, and the cumulative LOH rate was not higher in patients non-deleted for 16q23.2. Conclusion These results emphasize the interest of 16q23.2 as an independent prognostic factor in high-grade prostate cancer, and suggest that this chromosomal region may contain a gene involved in tumor progression. © 2005 Wiley-Liss, Inc.

4569 Background: We have shown a direct relation between positive margin (PM), morbidity outcomes and surgeon volume, technique after radical prostatectomy (RP). Significant variation occurs even among high volume providers. Our aim was to analyze the surgeon effects on cancer control after RP. Methods: We evaluated 8196 consecutive cT1–3NxMx naive men who underwent RP by one of 76 surgeons within 4 institutions between 1987 and 2003. We calculated the 5-yr probability of recurrence (BCR, PSA elevation >0.4 ng/ml × 2 or initiation of secondary therapy for a PSA rise) for each surgeon assuming a log-logistic survival distribution. A meta-analysis controlling for case mix: PSA, Gleason score, stage, PM and surgical expertise (i.e. cumulative number of surgeries performed) to evaluate for differences in BCR rates between surgeons was performed. We applied the I-square statistic to determine what proportion of the variation represented genuine differences v. chance alone. Results: 33 surgeons performed > 40 RP with 17 surgeons having > 100 procedures during the study period. BCR events were recorded in 1361 patients. The overall 5-yr freedom from BCR with 2524 patients remaining at risk was 80% (79%, 81%) . Extracapsular extension, seminal vesicle invasion, nodal metastasis, PM, Gleason score and PSA were independent predictors of BCR. The surgical volume also correlated independently with BCR. Importanntly we found significant variability on freedom from BCR between high volume surgeons. The I-squared statistic from the meta-analysis was 0.63. That is, approximately 63% of the difference in BCR rates among surgeons can be explained by genuine differences in surgical skill and approach, and approximately 37% is compatible with chance alone. For a sensitivity analysis, we repeated the analysis excluding surgeons who performed less than 100 procedures. In this sub-analysis, the I-squared statistic remained very significant at 0.48. Conclusions: Our data shows that in men treated by RP, the BCR outcomes of men are not exclusively determined by the biology and stage of prostate cancers (explained in most models), but to the surgical skill. Clinical trials evaluating BCR outcomes must prove equivalency among providers so that results are not biased by them. No significant financial relationships to disclose.