Relationship and predictive role of the dual expression of FGFR and IL-8 in metastatic renal cell carcinoma treated with targeted agents

Background/Aim: The expression of IL-8 and FGFR has been related to prognosis and pathological features in renal cell carcinoma. We investigated the relationship between IL-8 and FGFR and the outcome in metastatic renal cell carcinoma (mRCC) patients. Materials and Methods: Clinical data and histological samples of patients affected by mRCC and treated with targeted agents were reviewed. The expression of proteins was assessed using immunohistochemistry. Results: FGFR1, FGFR2, and IL-8 were found to be expressed in 16%, 30%, and 50% of cases, respectively. Significant correlations were found between selected proteins. A lack of expression of FGFR2 and IL8 was found to be correlated with increased progression-free survival (PFS). The survival rate at 24 months was 44%, 38%, and 79% of those expressing both, one, or none of the evaluated proteins, respectively (p=0.047). Conclusion: This analysis found a relationship between the expression of IL-8 and FGFR2 in mRCC patients treated with targeted agents

The Role of Fast and Deep PSA Response in Castration-sensitive Prostate Cancer

Background: Outcomes of castration-sensitive prostate cancer (CSPC) have improved owing to new therapies and early treatment, previously reserved for castration-resistant disease (CRPC). Prostatic-specific antigen (PSA) remains the most used marker to follow-up patients under treatment, but only limited data are available about the prognostic role of its changes over time and the impact of response to subsequent therapies. This analysis aims to assess the prognostic role of the magnitude and velocity of PSA response in CSPC and describe how this may affect the outcome to subsequent treatment outcomes in CRPC. Patients and methods: A retrospective analysis was performed on patients with de novo CSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. PSA response (PSA50), defined as a decrease > 50% compared to baseline, PSA velocity (PSAv), defined as any decrease in PSA levels over time and the deep and fast PSA response (4mPSA50), defined as the PSA response reached within the threshold of 4 months from the beginning of androgen deprivation therapy (ADT) have been evaluated for their impact on survival. Survivals were estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional-hazard models, stratified according to baseline characteristics, were used to estimate hazard ratios for overall survival (OS). Results: A totals of 94.4% of patients had PSA50, which was correlated to longer OS compared to patients without PSA50 (56.0 vs. 14.8 months; p<0.001). The median PSAv was 6.9 (ng/dl)/month, which was predictive for longer OS: Each decrease of 1 (ng/dl)/month was able to improve OS by 0.2% (HR=0.998, 95%CI=0.997-1.000; p=0.008). A total of 47.9% of patients reached 4mPSA50, with a median OS and progression-free survival (PFS) to ADT-based therapy of 101.0 and 23.4 months compared to 41.9 and 11.0 months for those who did not (p<0.001), respectively. The independent prognostic role of 4mPSA50 was retained even when evaluated in multivariable analysis adjusted for other baseline characteristics and early docetaxel for CSPC. In CRPC, 4mPSA50 evaluated during CSPC retains its prognostic role even if it does not predict a different outcome between patients treated with abiraterone/enzalutamide or taxanes. Conclusion: Achieving a deep and fast PSA response correlates with a better outcome in patients with de novo mCSPC, also positively influencing the prognosis of the subsequent first-line therapy for CRPC disease

Use of adjuvant chemotherapy after surgery in patients with colon cancer

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Clinical experience with everolimus in the second-line treatment of advanced renal cell carcinoma

Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR-I) and is currently approved for the treatment of metastatic renal cell carcinoma (mRCC) after failure of first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI). In this narrative review, we aim to report the available evidence about the use of everolimus as second-line therapy for mRCC. A literature search was performed using PubMed/MEDLINE and abstracts from major conferences on clinical oncology as sources. We report data from prospective as well as retrospective and real world data studies and we analyze the safety and efficacy profile of everolimus as second-line therapy for mRCC. Although different drugs are currently available for the second-line treatment of mRCC, everolimus represents a feasible and safe option in this setting, especially for patients who have experienced high-grade toxicity or are still carrying TKI-related toxicities from first-line treatment

Targeted Approaches in Metastatic Castration-Resistant Prostate Cancer: Which Data?

Prostate cancer is the second most common diagnosed cancer and the fifth leading cause of cancer-related deaths in men worldwide. Despite significant advances in the management of castration-sensitive prostate cancer, the majority of patients develop a castration-resistant disease after a median duration of treatment of 18–48 months. The transition to a castrate resistance state could rely on alternative survival pathways, some related to androgen-independent mechanisms. Although several agents have been approved in this setting, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Recent studies revealed some of the complex pathways underlying inherited and acquired mechanisms of resistance to available treatments. A better understanding of these pathways may lead to significant improvements in survival by providing innovative therapeutic targets. The present comprehensive review attempts to provide an overview of recent progress in novel targeted therapies and near-future directions

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

Burned-Out Testicular Cancer: Really a Different History

Two or more histological types characterize more than 60% of testicular germ cell tumors (GCTs). Burned-out testicular tumor refers to partial or complete histological regression of the primary testicular lesions. The most frequent GCT type involved in this kind of histological regression is choriocarcinoma, followed by embryonal carcinoma. To our knowledge, there are no cases of the burned-out phenomenon in teratoma. We report a case of a 19-year-old man presenting to our institute with a right testicular lesion, evidence of mediastinal and abdominal lymph node metastasis, and high levels of GCT serum biomarkers. After orchiectomy, the histopathological examination showed a mixed GCT: mature teratoma, immature teratoma, and histological features of testicular cancer regression (burned-out phenomenon). The patient underwent first-line chemotherapy (BEP regimen) which resulted in a complete instrumental and biochemical response after 4 cycles. Teratoma is considered a less aggressive type of GCT. In this particular case, metastatic disease seems to result from non-germ cell components which underwent early spontaneous regression

Second-line therapy for metastatic urothelial carcinoma: Defining the best treatment option among immunotherapy, chemotherapy, and antiangiogenic targeted therapies. A systematic review and meta-analysis

There is no second-line standard of care universally accepted for platinum-refractory metastatic urothelial carcinoma. Immunotherapy and anti-VEGF(R) targeted therapies are 2 emerging strategies with promising though inconclusive results. We perform a systematic meta-analysis to assess the available options. We searched MEDLINE/PubMed, the Cochrane Library, and American society of clinical oncology (ASCO) Meeting abstracts to identify prospective studies. Data extraction was conduced according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The measured outcomes were overall survival (OS) and progression free survival (PFS). Seven randomized controlled trials were selected for final analysis, with a total of 2,451 evaluable patients. Chemotherapy with vinflunine did not reduce the risk of progression (HR = 1.11; 95%CI 0.78-1.57; P = .56) or death (HR = 0.97; 95%CI 0.70-1.34; P = .87) compared to taxanes. Immunotherapy with anti-PD-1/PD-L1 mAb improved OS over chemotherapy (HR = 0.81; 95% CI 0.71-0.92; P<.0009). The OS benefit of immunotherapy was retained when compared to taxanes, but not compared to vinflunine, although without a significant difference between the 2 subgroups (P = .30). A lack of PFS (HR = 0.73; P = .08) and OS (HR = 1.0; P = .99) benefit was observed with an anti-VEGF(R) plus chemotherapy compared to chemotherapy alone. No PFS (P = .14) or OS (P = .13) differences were detected when comparing anti-VEGF(R) ± chemotherapy and immunotherapy. Immunotherapy significantly improved OS compared to chemotherapy in metastatic urothelial carcinoma unselected for PD-L1 status. The addition of anti-VEGF(R) to chemotherapy did not provide any statistically significant benefit in terms of PFS or OS. Single agent taxanes or vinflunine can be considered given their similar efficacy but different toxicity profiles

Immunotherapy versus standard of care in metastatic renal cell carcinoma. A systematic review and meta-analysis

Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS. We performed a meta-analysis of randomized trials comparing immunotherapy to standard of care (SOC) in mRCC