Marcus Vinicius Sadi

Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

BackgroundProstate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer.MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%).ResultsThe final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26).ConclusionOverall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.

Hypofractionated external-beam radiation therapy (HEBRT) versus conventional external-beam radiation (CEBRT) in patients with localized prostate cancer: a systematic review and meta-analysis

Background The purpose of this work was to conduct a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy and side effect profile of hypofractionated versus conventional external-beam radiation therapy for prostate cancer. Methods Several databases were searched, including Medline, EmBase, LiLACS, and Central. The endpoints were freedom from biochemical failure and side effects. We performed a meta-analysis of the published data. The results are expressed as the hazard ratio (HR) or risk ratio (RR), with the corresponding 95% confidence interval (CI). Results The final analysis included nine trials comprising 2702 patients. Freedom from biochemical failure was reported in only three studies and was similar in patients who received hypofractionated or conventional radiotherapy (fixed effect, HR 1.03, 95% CI 0.88–1.20; P = 0.75), with heterogeneity [χ2 = 15.32, df = 2 (P = 0.0005); I2 = 87%]. The incidence of acute adverse gastrointestinal events was higher in the hypofractionated group (fixed effect, RR 2.02, 95% CI 1.45–2.81; P < 0.0001). We also found moderate heterogeneity on this analysis [χ2 = 7.47, df = 5 (P = 0.19); I2 = 33%]. Acute genitourinary toxicity was similar among the groups (fixed effect, RR 1.19, 95% CI 0.95–1.49; P = 0.13), with moderate heterogeneity [χ2 = 5.83, df = 4 (P = 0.21); I2 = 31%]. The incidence of all late adverse events was the same in both groups (fixed effect, gastrointestinal toxicity, RR 1.17, 95% CI 0.79–1.72, P = 0.44; and acute genitourinary toxicity, RR 1.16, 95% CI 0.80–1.68, P = 0.44). Conclusion Hypofractionated radiotherapy in localized prostate cancer was not superior to conventional radiotherapy and showed higher acute gastrointestinal toxicity in this meta-analysis. Because the number of published studies is still small, future assessments should be conducted to clarify better the true role of hypofractionated radiotherapy in patients with prostate cancer.

Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis

Objective Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA) and Western Europe. Androgen-deprivation therapy alone (ADT) remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT) that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel) for metastatic hormone-naive prostate cancer (mHNPC). Methods Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (95% CI). Results The final analysis included 3 trials comprising 2,264 patients (mHNPC). Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001), and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). The biochemical progression-free survival (bPFS) also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001), also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%). Finally, the combination of ADT with docetaxel showed a superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%). A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002). In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). Regarding adverse events and severe toxicity (grade ≥3), the group receiving the combined therapy had higher rates of neutropenia, febrile neutropenia and fatigue. Conclusion The combination of ADT with docetaxel improved the clinical progression-free survival, bPFS and OS of patients with mHNPC. A superior OS was seen especially for patients with metastatic and high-volume disease. This contemporary combination therapy may now be offered as a first-line treatment for selected patients.

Immunotherapy with Sipuleucel-T (APC8015) in patients with metastatic castration-refractory prostate cancer (mCRPC): a systematic review and meta-analysis.

OBJECTIVE To perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of Sipuleucel-T versus placebo for asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer (mCRPC). MATERIALS AND METHODS Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), time to progression (TTP) and side effects. We performed a meta-analysis (MA) of the published data. The results are expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% confidence intervals (CI 95%). RESULTS The final analysis included 3 trials comprising 737 patients. The TTP was similar in patients who received Sipuleucel-T or placebo (fixed effect: HR = 0.89; CI 95% = 0.75 to 1.05; p = 0.16), with no heterogeneity detected on this analysis (Chi2 = 2.14, df = 2 (P = 0.34); I2 = 6%). The results showed a higher overall survival in patients treated with Sipuleucel-T (fixed effect: HR = 0.74; CI 95% = 0.61 to 0.89; p = 0.001; NNT = 3). We found no heterogeneity on this analysis either (Chi2 = 1.46, df = 2 (P = 0.48); I2 = 0%). The incidence of adverse events (grade > 3) was the same in both groups. CONCLUSION Sipuleucel-T prolongs overall survival in patients with asymptomatic or minimally symptomatic mCRPC.

Prostate cancer proteomics: clinically useful protein biomarkers and future perspectives

ABSTRACT Introduction: Although prostate cancer constitutes one of the most important, death-related diseases in the male population, there is still a need for identification of sensitive biomarkers that could precociously detect the disease and differentiate aggressive from indolent cancers, in order to decrease overtreatment. Proteomics research has improved understanding on mechanisms underlying tumorigenesis, cancer cells migration and invasion potential, and castration resistance. This review has focused on proteomic studies of prostate cancer published in the recent years, with a special emphasis on determination of biomarkers for cancer progression and diagnosis. Areas covered: Shotgun and targeted-proteomic studies of prostate cancer in different matrices are reviewed, i.e., prostate tissue, prostate cell lines, blood (serum and plasma), urine, seminal plasma, and exosomes. The most important biomarkers for cancer diagnosis and aggressiveness characterization are highlighted. Expert commentary: In general, results demonstrate alteration in cell cycle control, DNA repair, proteasomal degradation, and metabolic activity. However, these studies suffer from low reproducibility due to heterogeneity of the cancer itself, as well as to techniques utilized for protein identification/quantification. Downstream confirmatory studies in separate cohorts are warranted in order to demonstrate accuracy of these results.

PSA screening for prostate cancer

Screening of prostate cancer with prostate-specific antigen (PSA) is a highly controversial issue. One part of the controversy is due to the confusion between population screening and early diagnosis, another derives from problems related to the quality of existing screening studies, the results of radical curative treatment for low grade tumors and the complications resulting from treatments that affect the patients quality of life. Our review aimed to critically analyze the current recommendations for PSA testing, based on new data provided by the re-evaluation of the ongoing studies and the updated USPSTF recommendation statement, and to propose a more rational and selective use of PSA compared with baseline values obtained at an approximate age of 40 to 50 years.

First brazilian consensus of advanced prostate cancer: recommendations for clinical practice

ABSTRACT Introduction Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. Objectives This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Materials and Methods Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. Results and Conclusions The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.

High-grade metastatic paratesticular cystadenocarcinoma

Paratesticular cystadenocarcinoma is a rare form of ovarian epithelial tumor, with less than forty cases reported to date.1 Clinical presentation is scrotal enlargement with no significant pain.2 Ultrasound often shows a hypoechoic vascularized mass, with variable amounts of hydrocele. CT and MRI are not able to differentiate this tumor from other differential diagnosis. When normal values of human chorionic gonadotropin and alphafetoprotein are seen associated with a high value of serum CA125, this disorder should be suspected and confirmed by immunohistochemistry (IHQ).1 Herein we report a case of metastatic presentation of a paratesticular cystadenocarcinoma.

Comparison of vaginal wall sling and modified vaginal wall sling for stress urinary incontinence

CONTEXT There are several controversies about which is the best form of surgical treatment for stress urinary incontinence in women. The vaginal wall sling in its original and modified form were presented by Raz as new options for treatment of these conditions, but there is a lack of comparative clinical trials using both techniques. OBJECTIVE To compare the effectiveness of the original and the modified vaginal wall sling. DESIGN A comparative, prospective, non-randomized clinical trial. SETTING Public and private health care units (Urology Division, Faculty of Medicine of the ABC Foundation, and Universidade Federal de São Paulo / Escola Paulista de Medicina). PARTICIPANTS Twenty patients with anatomical and intrinsic sphincter deficiency stress urinary incontinence were surgically treated for evaluating the initial results of the vaginal wall sling, from February 5, 1994, to June 27, 1996. INTERVENTIONS The patients were divided into two groups. Group A (n = 10) were treated with the original vaginal wall sling. Group B (n = 10) were treated with the modified vaginal wall sling. Both groups were statistically similar according to clinical and urodynamic parameters. MAIN MEASUREMENTS Cure and complication rates. RESULTS Follow-up ranged from 19 to 43 months (median = 28) for group A. The overall cure rate was 70%. Fifty per cent of the patients had urinary retention of 7 to 35 days. There were no major complications. Follow-up ranged from 14 to 26 months (median = 18) for Group B. The cure rate was 80%. Two patients had urinary retention of 7 and 55 days. There were no major complications. CONCLUSIONS The vaginal wall sling is as effective as the modified vaginal wall sling but has a higher rate of urinary retention.