PD-L1 expression and correlation with outcome in muscle-invasive and metastatic urothelial carcinoma: review and critical discussion

Immunotherapy with checkpoint inhibitors including atezolizumab, pembrolizumab and nivolumab has become an essential pillar in the management of muscle invasive and metastatic urothelial carcinoma. The field has evolved quickly in the past few years and several early beliefs have recently been upended. One such belief relates to the predictive value of PD-L1 expression based on immunohistochemistry. Nevertheless, requirements for PD-L1 expression from regulatory bodies still restrict the use of checkpoint inhibitors in urothelial carcinoma. This article provides a critical review of the available data from the registration trials on which the current regulations have been based with the conclusion that a review of the current approval status incorporating PD-1 expression is warranted

Prostate Cancer and Sleep Disorders: A Systematic Review.

Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments

Safety and efficacy of pazopanib in heavily pretreated and treatment-naive patients with metastatic renal cell carcinoma (mRCC): A single center experience of the Medical University of Vienna, Austria.

e15090 Background: Treatment with pazopanib was shown to improve objective response rates (ORR) and progression free survival (PFS) when compared to placebo in treatment-naïve or cytokine-pretreated patients with mRCC. We assessed the efficacy and safety of pazopanib in an unselected group of mRCC-patients at the Medical University of Vienna. Methods: Medical records of all patients who were treated with pazopanib between June 2010 and January 2012 were retrospectively reviewed. Pazopanib was prescribed at a dose of 800 mg daily. Treatment was given until disease progression or unacceptable toxicity. ORR was assessed by RECIST criteria. PFS and overall survival (OS) were calculated from the first day of pazopanib until progression and/or death, respectively. Results: Forty patients with a median age of 69 years (range 47-82) are currently evaluable for this analysis. The majority of patients (61%) presented with an ECOG Performance status of 0 and were classified as intermediate risk (55%) according to the MSKCC risk group classification. All patients had undergone nephrectomy and the majority (75%) had predominantly clear cell tumors. Most of the patients (66%) were diagnosed with three or more metastatic sites. Eighty percent of the patients were heavily pretreated, most commonly with three or more different types of targeted agents. Eight patients (20%) received pazopanib in first-line. Objective remission and disease stabilization were observed in 27% and 30% of the entire population. PFS and OS were 5 months (95%CI 3.07-6.86) and not reached, respectively. The most commonly observed all grade toxicities included fatigue (97%), anorexia (78%), hypertension (82%), diarrhoea (73%), nausea (62%) and vomiting (54%). The most common grade 3 or 4 toxicities were fatigue (68%), hypertension (47%) and diarrhoea (29%). Conclusions: Pazopanib appears effective in the setting of extensively pretreated patients. A later stage of the disease might have led to the unexpected higher incidence of off-target side effects such as fatigue and gastro-intestinal symptoms. </jats:p

How Does Environmental and Occupational Exposure Contribute to Carcinogenesis in Genitourinary and Lung Cancers?

Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages

Safety and efficacy of axitinib in pretreated patients with metastatic renal cell carcinoma: A single center experience of the Medical University of Vienna, Austria.

e15535 Background: Axitinib is a highly selective inhibitor of VEGFR-1, 2 and 3 and has recently been approved for second-line treatment of metastatic renal cell cancer (mRCC). We present data of 43 patients treated with axitinib in second-line and beyond. Methods: Medical records of all patients who were treated with axitinib between July 2009 and December 2012 were retrospectively reviewed. Axitinib was prescribed at a dose of 5 mg bid and escalated to 7 or 10 mg bid in the absence of hypertension and other dose-limiting toxicities. Objective response rate (ORR) was assessed by RECIST. Progression free survival (PFS) and overall survival (OS) were calculated from the first day of axitinib until progression and/or death, respectively. Results: Fourty-three patients with a median age of 65 years (range: 17-84) are currently evaluable for analysis. The majority of patients (58.1%) had an ECOG Performance status of 0 and were classified MSKC- intermediate risk (62.8%). All patients had undergone surgery for the primary tumor and 53.5% had three or more metastatic sites. Fifty-five percent of the patients received axitinib in third or fourth-line (14% and 41.9%, respectively). Prior therapies included sunitinib (86%), everolimus (35%) and pazopanib (35%) and 62.8% had progressed on sunitinib before axitinib was initiated. Objective remission and disease stabilization were observed in 14.3% and 40% of the entire population. The median PFS and OS were 6.8 months (95% CI: 5.5 – 8.0) and 17.2 months (95% CI: 10.8 – 23.6), respectively. Dose escalation to 7 or 10 mg bid was feasible in 40% of the patients. Fatigue (76.7%), hypertension (65.1%) and hypothyroidism (53.5%) were among the most commonly observed all grade toxicities. Conclusions: Axitinib showed considerable efficacy in both second-line and beyond second-line patients. Generous dose escalation based on a “treat to hypertension”-concept may have led to a longer PFS than previously reported from a purely VEGFR-TKI-refractory patient population. </jats:p