Post-docetaxel therapy in castration resistant prostate cancer – the forest is growing in the desert

In Europe, prostate cancer is the most common cancer among men with 382.000 new cases and 89.000 deaths annually. Historically, androgen deprivation therapy and docetaxel based chemotherapy were the only treatments able to improve survival. Two studies have been published during last few months regarding the management of castration resistant prostate cancer (CRPC) progressed after docetaxel: for the first time second line therapies have been demonstrated to improve prognosis of these patients. The relevance of these trials is the reintroduction of chemotherapy and hormonal therapy in a disease once considered chemotherapy and castration resistant. All these data may change the traditional approach to CRPC but no evidences have came out from recently closed or ongoing clinical trials about the therapeutic algorithm. How to get oriented in this forest? We propose that patient’s conditions, response and toxicities reported with previous treatments and, above all, dynamics and evolution of disease may influence the choice of subsequent therapies in docetaxel progressed CRPC

Clinical and pathological features of primary renal synovial sarcoma: analysis of 64 cases from 11 years of medical literature.

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Primary renal synovial sarcoma is a very rare renal neoplasm. Since 2000, when this tumour was first described, only case reports have been published in the medical literature. This study is the first to describe the clinical and pathological features of primary renal synovial sarcoma and it found a relationship between these characteristics. Median overall and disease-free survival were reported, and the risk of relapse for patients with non-metastatic disease at diagnosis was found to be 36%. Different histological sub-types, also described in other synovial sarcomas, were found in primitive renal tumours and directly related to tumour extension at diagnosis, different patterns of immunohistochemical stain and genetic alterations. OBJECTIVE To describe, for the first time, the clinical characteristics of primary renal synovial sarcoma (SS) and to examine the association of histological features with the expression of immunohistochemical markers. PATIENTS AND METHODS We collated published data on all cases of primary renal SS, from its first description in 2000 to September 2011. Data on clinical and pathological characteristics were extracted and used to create a database. Disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method with Rothman's 95% confidence intervals (CIs) and compared across the groups using the log-rank test. The associations between tumour extension and histological features were evaluated using the non-parametric Spearman rank test. A chi-squared test was used to assess the differences between groups. RESULTS In the overall cohort, the median OS was 48 months (95% CI, 14.1-81.9). Cox analysis showed that the risk of death at diagnosis was greatly increased in patients with metastatic disease compared with those with non-metastatic disease (hazard ratio [HR]: 343.9, 95% CI, 2.8-42 000; P= 0.017). The median DFS was 33.0 months (95% CI, 16.8-49.2), and patients who develop metastatic disease have a very poor prognosis with a median survival of 6 months (95% CI, 5.1-6.9). Microscopic features were monophasic, biphasic and poorly differentiated synovial sarcoma in 76, 16 and 8% of patients, respectively. Significant differences in expression of immunohistochemical markers or genetic mutation were found between different subtypes. CONCLUSIONS Despite its retrospective nature, this study shows that renal SS comprises different histological subtypes, which are characterized by specific immunohistochemical stains and by specific translocations. When diagnosed at metastatic stage, the prognosis was very poor compared with that for non-metastatic disease, even though one out of three patients with non-metastatic disease had disease relapse. Cooperative efforts and publication of cases with adequate follow-up are necessary to better define prognosis and therapeutic strategies for this rare disease. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL

Clinical and Pathological Features of Primary Neuroectodermal Tumor/Ewing Sarcoma of the Kidney

OBJECTIVE To collect and analyze clinical and pathological features of primitive neuroectodermal tumor (PNET)/Ewing sarcoma (EWS), a rare tumor occurring most commonly in bone and soft tissues of young people, which rarely occurs as a primary renal neoplasm and exhibits highly aggressive biological behavior. METHODS All cases of PNET/EWS published from 1975 to February 2012 were collected. When available, clinical and pathological data were extracted for each case. Survivals were estimated with the Kaplan-Meier method and compared with the log-rank test with 95% confidence interval (CI). RESULTS A total of 116 cases were found. All patients had clinical symptoms as first presentation of disease such as pain (54%), hematuria (29%), and bulky renal mass (28%). Sixty-six percent of patients had stage IV disease at diagnosis. Median disease-free survival (DFS) was 5.0 months (95% CI 2.4-7.6). The probability to be alive at 18 months was 60% and 85% for patients with metastatic disease (M1) or not (M0) at diagnosis, respectively. Median overall survival (OS) was 24 months (95% CI 4.5-15.1) in patients with M1 disease, whereas it was not reached in patients with M0 disease (P<.001). In patients with M0 disease, 50% received neoadjuvant chemotherapy and the 12-month OS was 93% compared to 75% of untreated patients (P=.092). In patients with M1 disease who underwent treatment, the median progression-free survival (PFS) was 22.0 months (95% CI 17.9-26.1) with a clinical benefit in 74% of cases. CONCLUSION Our findings suggest that PNET/EWS is a rare aggressive tumor affecting principally young people, with a poor prognosis for patients with M1 disease; chemotherapy is an effective strategy in M1 disease and probably also in M0 disease. UROLOGY 82: 382-386, 2013. (C) 2013 Elsevier Inc

Dynamic contrast-enhanced magnetic resonance imaging in the early evaluation of anti-angiogenic therapy in metastatic renal cell carcinoma.

Aim: To evaluate the efficacy of dynamic contrast-enhanced magnetic resonance (DCE-MR) in the response to anti-angiogenic-targeted agents in patients with metastatic renal cell cancer (mRCC). Patients and Methods: Twenty-eight consecutive patients with sub-diaphragmatic metastases from mRCC were included in the protocol after signed informed consent. Baseline characteristics were collected and patients were first evaluated with a baseline computed tomography (CT) and DCE-MR, subsequently with a new DCE-MRI after 28 days of therapy and followed-up with CT until progression. Treatments were administered at standard doses. The changes of peak enhancement (Delta PE) and of the sum of longest tumor diameters (Delta LTD) were related to progression-free survival (PFS) and overall survival (OS). Results: The median PFS was 11.4 months [95% Confidence Interval (CI): 7.9-14.7 months) and the parametric two-tailed Pearson's test showed a positive correlation between the median Delta PE and the median PFS (rp=0.809; p=0.015); no significant correlation was found between the median Delta LTD and the median PFS (rp=-0.446; p=0.27). The median OS was 23.3 months (95% CI: 13.6-33.0 months) and no significant correlation was found with the median Delta PE (rp=0.218; p=0.60) or with the median Delta LTD (rp=0.012; p=0.98). Conclusion: The APE but not the Delta LTD was found to be significantly related to PFS; these preliminary results suggest extending the number of patients and investigating the possible relationship with other tumor characteristics and MRI parameters

Medical strategies for treatment of castration resistant prostate cancer (CRPC) docetaxel resistant.

Current landscape of treatment of castration-resistant prostate cancer (CRPC) has recently changed. Cabazitaxel, a new taxane with potential antineoplastic activity, has been approved by Food and Drug Administration (FDA) after docetaxel failure. In a phase III trial, cabazitaxel showed increased overall survival (OS) compared with mitoxantrone (15.1 vs. 12.7 mo, HR 0.70, 95% CI 0.59-0.83, p < 0.0001). Furthermore, chemotherapy is not the only strategy available: several studies have shown as CRPC remains dependent on androgen receptor function for growth. Abiraterone acetate, an irreversible inhibitor of CYP17, has also been approved by FDA after docetaxel failure. In a phase III trial comparing abiraterone acetate to placebo, abiraterone showed improvement in OS (14.8 vs. 10.4 mo, HR 0.65, 95% CI 0.54-0.77; p < 0.0001). This review will discuss current options and the ongoing trials for second-line treatment of CRPC including chemotherapy, hormonal therapies, antiangiogenetic and immune strategies

Multimodality Treatment of Gynecomastia in Patients Receiving Antiandrogen Therapy for Prostate Cancer in the Era of Abiraterone Acetate and New Antiandrogen Molecules

Gynecomastia is a pathological enlargement of male breasts due to hormonal imbalance and elevation of estrogens at the expense of testosterone. It is very important to diagnose this disease precociously because it can be the expression of different underlying pathologies. Besides genetic, chromosomal or chronic diseases, drugs often represent the principal cause of this hormonal disequilibrium. In the elderly population, antiandrogen therapy for prostate cancer frequently induces gynecomastia, thus negatively affecting the patients' compliance to treatment because of physical and psychological discomfort deriving from this condition; gynecomastia can in fact be associated with severe breast pain, and it can modify how patients see their own body. During the past decades and even today, many different surgical, radiotherapeutic or clinical approaches have been proposed to prevent or treat this hypertrophy. This article focuses on gynecomastia associated with antiandrogen-based hormonal treatment and shortly reviews the currently most often used therapeutic options for preventing and treating this pathology. Copyright © 2012 S. Karger AG, Basel

Immune System and DNA Repair Defects in Ovarian Cancer: Implications for Locoregional Approaches

In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects in HR systems are associated more frequently with higher tumor infiltrating lymphocytes, providing a rationale for developing combination therapy with immune-modulating agents and PARP inhibitors. Again, locoregional therapies combining heat shock and chemotherapy delivery have been shown to induce an anticancer immune response in vitro. Thus, the potential for locoregional therapeutic approaches that may impact the immune system, perhaps in combination with immune-modulating agents or PARP inhibitors, needs to be further explored. With this premise, we reviewed the main biological and clinical data demonstrating a strict interplay between the immune system, DNA repair mechanisms, and intraperitoneal therapies in ovarian cancer, with a focus on potential future therapeutic implications

Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

Gynecological tumors are malignancies with both high morbidity and mortality. To date, only a few chemotherapeutic agents have shown efficacy against these cancer types (only ovarian cancer responds to several agents, especially platinum-based combinations). Within this context, the discovery of immune checkpoint inhibitors has led to numerous clinical studies being carried out that have also demonstrated their activity in these cancer types. More recently, following the development of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, this strategy was also tested in solid tumors, including gynecological cancers. In this article, we focus on the molecular basis of gynecological tumors that makes them potential candidates for immunotherapy. We also provide an overview of the main immunotherapy studies divided by tumor type and report on CAR technology and the studies currently underway in the area of gynecological malignancies