Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Topographic distribution of first landing sites of lymphatic metastases from patients with renal cancer.

INTRODUCTION AND OBJECTIVE: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. MATERIALS AND METHODS: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). RESULTS: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22-63.12%) and hilar (31.42%; 95% CI 17.4-49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7-43.2%), hilar (26.82%; 95% CI 14.7-43.2%), interaortocaval (26.82%; 95% CI 14.7-43.2%), and paracaval (17.07%; 95% CI 7.6-32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. CONCLUSIONS: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials.

TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality. METHODS AND ANALYSIS: Eligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial. ETHICS AND DISSEMINATION: NINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study. TRIAL REGISTRATION NUMBER: ANZCTN 12615000223538.

Robot-assisted partial nephrectomy: How to minimise renal ischaemia.

Renal ischaemia research has shown an increase in renal damage proportional to ischaemic time. Therefore, we assessed the importance of renal ischaemic times for warm and cold ischaemia approaches, and explored the different surgical techniques that can help to minimise renal ischaemia in robot-assisted partial nephrectomy (RAPN). Minimising renal ischaemia during nephron-sparing surgery (NSS) is a key factor in preserving postoperative renal function. Current data support a safe warm ischaemia time (WIT) of ≤25 min and cold ischaemic time of ≤35 min, resulting in no significant deterioration in renal function. In general, patients undergoing NSS have increased comorbidities, including chronic kidney disease, and in these patients it is difficult to predict their postoperative renal function recovery. With RAPN, efforts should be made to keep the WIT to <25 min, as minimising the ischaemic time is vital for preservation of overall renal function and remains a modifiable risk factor. Parenchymal or segmental artery clamping, early unclamping or off-clamp techniques can be adopted when ischaemic times are likely to be >25 min, but may not lead to superior functional outcome. Careful preoperative planning, tumour factors, and meticulous surgical technique are critical for optimum patient outcome.

Robotic-assisted Laparoscopic Partial Nephrectomy in a Horseshoe Kidney. A Case Report and Review of the Literature.

Horseshoe kidney is a rare renal fusion anomaly, and because of limited mobilization of the kidney and its multiple arterial blood supplies, minimally invasive surgery for renal tumors can be challenging. We describe a case of a right-side oncocytoma in a horseshoe kidney managed robotically and review the literature of robotic-assisted laparoscopic surgical resection of kidney tumors in renal fusion anomalies. Robotic-assisted laparoscopic partial nephrectomy in a horseshoe kidney is feasible. Fusion-related limited mobility during the procedure, as well as an extremely variable blood supply, require meticulous planning. Multi-phase computed tomography and interactive 3D anatomical models are helpful tools to prepare for surgery.

"Researching the Research" in Prostate Cancer: A Comparative Bibliometric Analysis of the Top 100 Cited Articles in the Field of Prostate Cancer.

BACKGROUND: To perform the first comparative bibliometric analysis of the "Top 100 (T100) cited articles in prostate cancer (PCa)". MATERIALS AND METHODS: A comprehensive search using the Web of Science Database (v 5.21) covering the Web of Science™ Core Collection, BIOSIS Previews, Central Contents Connect, KCI-Korean Journal Database, MEDLINE, SciELO Index (February 2016) was performed, for all articles relevant to PCa. RESULTS: The T100 were cited 582 to 3,387 times, and were published from 1966 to 2012. The top 3 subcategories associated with PCa included: genetics/biomarkers (n = 34), management (n = 25), and physiology (n = 11). T100 contributions from USA (n = 86), were most prominent. If the regional citation was corrected for percentage on research (citation record/percentage gross domestic product on research) a variation in the ranking was noted. CONCLUSION: The first bibliometric analysis in the field of PCa is presented. Regions that predominate the T100, include the United States and Europe. Articles published in higher impact factor journals, in English medium and content related to PCa research associated with genetics/bio-markers have the highest citation potential.

Radical nephrectomy and vena caval thrombectomy with the use of cardiopulmonary bypass.

BACKGROUND: This study aimed to report on the experience of a single surgeon in a regional Australian centre with radical nephrectomy and vena caval thrombectomy with the use of cardiopulmonary bypass. METHODS: Fifteen consecutive patients undergoing radical nephrectomy and vena caval thrombectomy with cardiopulmonary bypass over a 13-year period were identified. Retrospective analysis of prospectively collected data was used. Data were collected on intra-operative and pathological findings as well as post-operative complications. Oncological outcomes and long-term follow-up were analysed retrospectively in this study. RESULTS: All patients had a radical nephrectomy and vena caval thrombectomy with cardiopulmonary bypass. The median operating time was 336 min (mean 326.1 min), and median transfusion of packed red blood cells was 8 units (mean 6.9). The median bypass time was 107 min (mean 112.3 min), and the median circulation arrest time was 25 min (mean 25.3 min). Median length of hospital stay was 11 days (mean 14.5 days). Minor complications were seen in two patients and major complications seen in six, with one intra-operative death. Disease recurrence was seen in 1 of 14 patients who were considered completely resected at the time of operation. The overall 5-year survival rate was 84%. Median follow-up was 32 months (range 0-158). Median survival time was 135 months. CONCLUSIONS: Radical nephrectomy with caval thrombectomy with cardiopulmonary bypass can be performed in a regional centre with acceptable post-operative morbidity and mortality. Long-term survival is possible in some patients.