Initial active surveillance for patients with metastatic renal cell carcinoma: 10 years' experience at a regional cancer Centre.

A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course and may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. To investigate this we sought to define outcomes of patients with mRCC suitable for initial AS. All patients with mRCC clinically selected for initial AS at the Edinburgh Cancer Centre between January 2010 and December 2020 were identified. Key inflammatory biomarkers (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein [CRP], albumin, corrected calcium) and the International Metastatic RCC Database Consortium (IMDC) risk score were measured. The relationship between these and time to systemic anticancer therapy (tSACT) and overall survival (OS) was analysed. Data were available for 160 patients. Estimated median overall survival was 88.0 (interquartile range [IQR] 34.0-127.0) months. Median tSACT was 31.8 (IQR 12.0-76.3) months. On multivariate analysis, only CRP was predictive of tSACT (HR 2.47 [95% CI:1.59-3.85] p < 0.001) and OS (HR 3.89 [95% CI:2.15-6.83] p < 0.001). Patients with CRP > 10 mg/L were more likely to commence SACT within 1 year than those with CRP≤10 mg/L (41% vs. 18%, Relative Risk 2.16 (95% CI:1.18-3.96) (p = 0.012)). IMDC risk score was not predictive of tSACT or OS. Active surveillance is an appropriate initial management option for selected patients with mRCC. CRP, a biomarker of systemic inflammation, may provide additional objective information to assist clinical decision-making in patients with mRCC being considered for initial AS. Although this is a retrospective observational study, the cohort is well defined and includes all patients managed with initial AS in an inclusive real-world setting.

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA).

BACKGROUND: Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. METHODS: NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. RESULTS: In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. CONCLUSIONS: NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. CLINICAL TRIAL REGISTRATION: NCT03494816.

Challenging presentations of germ cell tumours in routine clinical practice.

Testicular cancer is the most common malignancy in young men. We discuss four cases of germ cell tumours (GCTs) presenting to general practitioners and physicians where there were notable preventable delays in the diagnosis and management. This diagnostic delay is associated with a more advanced stage of disease, and subsequent increased treatment-related morbidity and decreased survival. Our series highlights the variety of ways in which GCTs may present and we discuss the importance of prompt diagnosis through a thorough history and examination, early measurement of serum tumour markers and appropriate multidisciplinary team discussion. GCTs are highly curable cancers in the majority of patients and delays in management can, therefore, have devastating consequences.

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma.

PURPOSE: Pembrolizumab, a programmed death 1 inhibitor, demonstrated promising single-agent activity in untreated patients with various cancer types. The phase II KEYNOTE-427 study evaluated efficacy and safety of single-agent pembrolizumab in treatment-naive patients with advanced clear cell renal cell carcinoma (ccRCC; cohort A) and advanced non-ccRCC (cohort B). Results of cohort A are reported. METHODS: In this open-label, single-arm phase II study, patients with advanced ccRCC received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. The primary end point was objective response rate by RECIST, version 1.1. RESULTS: In the total population (N = 110), median time from enrollment to data cutoff was 35.9 (range, 29.5-40.3) months. Objective response rate was 36.4% with four (3.6%) complete responses and 36 (32.7%) partial responses; disease control rate was 58.2% (95% CI, 48.4 to 67.5). Most patients (68.2%) had a decrease in target lesions, including 30.9% with a reduction ≥ 60%. Median duration of response was 18.9 (range, 2.3-37.6+) months; 64.1% of responders had a response ≥ 12 months (Kaplan-Meier). Median progression-free survival was 7.1 months (95% CI, 5.6 to 11.0). Median overall survival was not reached; 12-month and 24-month overall survival rates were 88.2% and 70.8%, respectively. Durable responses were observed across all International Metastatic RCC Database Consortium categories. Grade 3-5 treatment-related adverse events were reported in 30.0% of patients, of which colitis and diarrhea were most frequent. CONCLUSION: Single-agent pembrolizumab showed promising antitumor activity as a first-line treatment in patients with advanced ccRCC, with durable responses across International Metastatic RCC Database Consortium categories. Safety and tolerability profile of pembrolizumab monotherapy was comparable to what has been previously described in other tumor types.

Testicular cancer: improving outcomes with national quality performance indicators.

Testicular cancer is the most common malignancy in young adult men. The prognosis is excellent in limited disease and cure is possible even in advanced disease. Quality performance indicators (QPI) are used in many developed countries as a measure of healthcare performance. We report and discuss the development of a national set of QPIs in Scotland for testicular cancer as a method of gathering demographic data and driving improvement in nationwide testicular cancer outcomes.

Five-year outcomes after iodine-125 seed brachytherapy for low-risk prostate cancer at three cancer centres in the UK.

OBJECTIVE: To report the outcomes of >1000 men with low-risk prostate cancer treated with low-dose-rate (LDR) brachytherapy at three large UK cancer centres. PATIENTS AND METHODS: A total of 1038 patients with low-risk prostate cancer (prostate-specific antigen [PSA] ≤10 ng/mL, Gleason score 6, ≤T2b disease) were treated with LDR iodine 125 (I-125) brachytherapy between 2002 and 2007. Patients were treated at three UK centres. PSA and clinical follow-up was performed at each centre. Biochemical recurrence-free survival was reported for the cohort. RESULTS: The median (range) PSA follow-up for the whole group was 5 years (4 months to 9 years). A total of 79 patients had biochemical failure, defined by a rise in PSA level: 16 patients fulfilled the ASTRO definition of biochemical failure, 25 patients fulfilled the Phoenix definition and 38 patients fulfilled both definitions. The 5-year biochemical relapse-free survival (bRFS) rate was 94.1% by the ASTRO definition and 94.2% by the Phoenix definition. The absence of neoadjuvant hormone therapy was predictive of inferior biochemical control as defined by the Phoenix definition (P = 0.033). CONCLUSIONS: Our prospective multicentre series showed excellent bRFS with LDR I-125 brachytherapy for patients with low-risk prostate cancer. Further work is necessary to define the role of neoadjuvant androgen deprivation therapy in combination with brachytherapy.