Systemic anticancer therapy for urothelial carcinoma: UK oncologists' perspective.

Urothelial carcinoma (UC) is a common cancer associated with a poor prognosis in patients with advanced disease. Platinum-based chemotherapy has remained the cornerstone of systemic anticancer treatment for many years, and recent developments in the treatment landscape have improved outcomes. In this review, we provide an overview of systemic treatment for UC, including clinical data supporting the current standard of care at each point in the treatment pathway and author interpretations from a UK perspective. Neoadjuvant cisplatin-based chemotherapy is recommended for eligible patients with muscle-invasive bladder cancer and is preferable to adjuvant treatment. For first-line treatment of advanced UC, platinum-eligible patients should receive cisplatin- or carboplatin-based chemotherapy, followed by avelumab maintenance in those without disease progression. Among patients unable to receive platinum-based chemotherapy, immune checkpoint inhibitor (ICI) treatment is an option for those with programmed death ligand 1 (PD-L1)-positive tumours. Second-line or later treatment options depend on prior treatment, and enfortumab vedotin is preferred after prior ICI and chemotherapy, although availability varies between countries. Additional options include rechallenge with platinum-based chemotherapy, an ICI, or non-platinum-based chemotherapy. Areas of uncertainty include the optimal number of first-line chemotherapy cycles for advanced UC and the value of PD-L1 testing for UC.

The impact of socioeconomic deprivation on mortality in cervical cancer patients in Cornwall (England).

OBJECTIVES: To assess the association between risk factors, including socioeconomic deprivation, and mortality, recurrence and chemo- or radiation toxicity in cervical cancer patients. METHODS: Retrospective study of cervical cancer patients diagnosed between January 2007 and July 2018. Patient characteristics and mortality data, including recurrence, were assessed, together with socioeconomic deprivation measures evaluated using the English Indices of Multiple Deprivation. Markov multi-state models were used to model mortality and recurrence, and logistic regression models were used to model chemo- or radiation toxicity. RESULTS: Included were 243 women with a median age of 49 years. A total of 57 patients died (23%), of which 41 due to cervical cancer, and 21 (9%) had recurrent disease. Hazard ratios (HR) showed no evidence of association between socioeconomic deprivation and cancer-specific hazard of mortality from diagnosis or recurrence, hazard of mortality due to other causes or hazard of cancer recurrence. Furthermore, there was no evidence of association between socioeconomic deprivation and chemo- or radiation toxicity (bowel, bladder or vaginal stenosis). CONCLUSIONS: No associations were found between socioeconomic deprivation and cancer mortality or recurrence in cervical cancer patients in the population of Cornwall. In addition, no association was found between socioeconomic deprivation and chemo- or radiation toxicity.

The role of sarcopenic obesity in high-grade endometrial cancer.

OBJECTIVE: To investigate the relationship between obesity and sarcopenia in relation to overall survival (OS) and disease-specific survival (DSS) in high-grade endometrial cancer patients. METHODS: We conducted a retrospective study in women diagnosed with high-grade endometrial cancer (EC) between February 2006 and August 2017 in the Royal Cornwall Hospital who had abdominal computerized tomography (CT)-scan as part of routine staging work-up. Sarcopenia was assessed by measuring psoas-, paraspinal- and abdominal wall muscles on CT and defined by skeletal muscle index ≤41 cm2 /m2 . Sarcopenic obesity was defined as sarcopenia combined with body mass index (BMI) ≥30 kg/m2 . RESULTS: A total of 176 patients with median age of 70 years and median BMI of 29.4 kg/m2 were included in the study. The majority of patients (38%) had endometrioid type histology. Sarcopenia was not associated with OS (P = 0.951) or DSS (P = 0.545) However, in multivariate analysis, sarcopenic obesity was associated with reduced OS in endometrioid endometrial cancer (EEC) patients (P = 0.048). CONCLUSION: Sarcopenic obesity is associated with OS in high-grade EEC patients, while sarcopenia without obesity is not related to OS or DSS in high-grade EC. In non-endometrioid endometrial cancer, there is no association between sarcopenic obesity and survival.

Obesity and visceral fat: Survival impact in high-grade endometrial cancer.

BACKGROUND: Obesity is an important risk factor for the development of endometrial cancer (EC). Recent data showed that body fat distribution might be more relevant than Body Mass Index (BMI). High visceral fat percentage was shown to be an independent predictor for survival in EC, but mainly included grade 1-2 EC. OBJECTIVE: To evaluate body fat distribution and its relation to outcome in high-grade endometrial cancer. METHODS: Retrospective study in women diagnosed with high-grade EC between February 2006 and August 2017 at the Royal Cornwall Hospital who had abdominal CT-scan as part of routine diagnostic work-up. Subcutaneous abdominal fat volumes and visceral abdominal fat volumes were quantified based on CT-scan measurements, and visceral fat percentage calculated. RESULTS: A total of 176 patients with high-grade EC were included. The median age was 70 years and median BMI was 29.4 kg/m2. The majority of patients had non-endometrioid endometrial cancer (NEEC; 62 %). High visceral fat percentage was associated with poor overall- and disease-specific survival (p = 0.006 and p = 0.026 respectively) in NEEC patients, but not in high-grade endometrioid EC (EEC). The most frequent obesity comorbidities hypertension and diabetes mellitus were significantly associated with high BMI and high visceral fat percentage. CONCLUSION: In high-grade EC, high visceral fat percentage was an independent predictor of poor survival only in NEEC. The strong correlation between high visceral fat and obesity-related comorbidities might be reflective of an unhealthy macroenvironment.

Prostate-specific antigen (PSA) bounce following salvage radiotherapy to the prostate bed in a patient with prostate cancer post-prostatectomy.

We present a case of prostate-specific antigen (PSA) bounce in a 76 year old man who underwent salvage radiotherapy to the prostate bed following biochemical relapse 6 years post-radical prostatectomy for a T2N0 Gleason grade 3 + 3 prostate adenocarcinoma; 10 months following completion of salvage radiotherapy for biochemical PSA recurrence of 0.2 µg/L. Following undetectable results (<0.03 µg/L), his PSA rose from 0.04 to 0.3 µg/L with no evidence of prostate cancer recurrence before returning to undetectable levels without medical intervention. This PSA 'bounce phenomenon' is well described following radiotherapy to an intact prostate and has been proposed to be the result of a late fibrotic effect on irradiated prostate tissue. To our knowledge, this is the first case published describing the effect in the post-prostatectomy setting. It highlights the importance of serial PSA monitoring to confirm biochemical relapse before committing the patient to androgen deprivation therapy (with its inherent risks and side effects).

Significance of Anemia in Outcomes After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Approximately one quarter of patients receiving neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer will be anemic at presentation. The outcomes of these anemic patients have historically been less favorable. We assessed the potential of anemia to act as an independent biomarker for a poor prognosis in patients with locally advanced rectal cancer. MATERIALS AND METHODS: We performed a retrospective, observational study of consecutive patients with locally advanced rectal adenocarcinoma who underwent NCRT from 2004 to 2009 at 3 English National Health Service trusts. The main outcomes were Rectal Cancer Regression Grade, mortality rate, and disease-free survival. These were compared between the anemic and nonanemic patients. RESULTS: A total of 273 patients were included. Of these patients, 63 (23%) had a hemoglobin level of < 120 g/L (anemic) at presentation. The Rectal Cancer Regression Grades were higher (less regression) in the anemic patients than in the nonanemic patients (χ2 = 10.14; P = .006). A subgroup analysis stratified by disease stage at presentation demonstrated less tumor regression in anemic patients with Dukes stage C disease (Dukes stage B, χ2 = 4.31, P = .12; Dukes stage C, χ2 = 5.36, P = .07). After adjusting for age, gender, and initial Dukes stage, the anemic patients demonstrated greater mortality rates than the nonanemic patients (hazard ratio, 1.73; 95% confidence interval, 1.05-2.86). The consistency with which the 2 independent reviewers were able to generate the rectal cancer regression grades from the historic pathology reports varied. Also, the subgroup analyses in the present study were often limited by low power. CONCLUSION: The present large UK study examined patients receiving NCRT for magnetic resonance imaging-proven, locally advanced rectal adenocarcinoma. Our findings have demonstrated that patients who were anemic at presentation have higher regression grades (less regression) in response to the treatment than nonanemic patients. This trend appeared to persist despite radiologic disease stage at presentation. Anemia at presentation was also associated with increased mortality rates compared with that of nonanemic patients.