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.

Clinical outcomes for men with positive surgical margins after radical prostatectomy-results from the South Australian Prostate Cancer Clinical Outcomes Collaborative community-based registry.

Objective: Positive surgical margins (PSMs) after radical prostatectomy (RP) indicate failure of surgery to completely clear cancer. PSMs confer an increased risk of biochemical recurrence (BCR), but how more robust outcomes are affected is unclear. This study investigated factors associated with PSMs following RP and determined their impact on clinical outcomes (BCR, second treatment [radiotherapy and/or androgen deprivation therapy], and prostate cancer-specific mortality [PCSM]). Methods: The study cohort included men diagnosed with prostate cancer (pT2-3b/N0/M0) between January 1998 and June 2016 who underwent RP from the South Australian Prostate Cancer Clinical Outcomes Collaborative database. Factors associated with risk of PSMs were identified using Poisson regression. The impact of PSMs on clinical outcomes (BCR, second treatment, and PCSM) was assessed using competing risk regression. Results: Of the 2827 eligible participants, 28% had PSMs-10% apical, 6% bladder neck, 17% posterolateral, and 5% at multiple locations. Median follow-up was 9.6 years with 81 deaths from prostate cancer recorded. Likelihood of PSM increased with higher pathological grade and pathological tumor stage, and greater tumour volume, but decreased with increasing surgeon volume (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.88-0.98, per 100 previous prostatectomies). PSMs were associated with increased risk of BCR (adjusted sub-distribution hazard ratio [sHR] 2.5; 95% CI 2.1-3.1) and second treatment (sHR 2.9; 95% CI 2.4-3.5). Risk of BCR was increased similarly for each PSM location, but was higher for multiple margin sites. We found no association between PSMs and PCSM. Conclusion: Our findings support previous research suggesting that PSMs are not independently associated with PCSM despite strong association with BCR. Reducing PSM rates remains an important objective, given the higher likelihood of secondary treatment with associated comorbidities.

Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial.

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3-18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159-2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer.

Usability, Acceptability, and Safety Analysis of a Computer-Tailored Web-Based Exercise Intervention (ExerciseGuide) for Individuals With Metastatic Prostate Cancer: Multi-Methods Laboratory-Based Study.

BACKGROUND: Digital health interventions such as tailored websites are emerging as valuable tools to provide individualized exercise and behavioral change information for individuals diagnosed with cancer. OBJECTIVE: The aim of this study is to investigate and iteratively refine the acceptability and usability of a web-based exercise intervention (ExerciseGuide) for men with metastatic prostate cancer and determine how well individuals can replicate the video-based exercise prescription. METHODS: A laboratory-based multi-methods design was used, incorporating questionnaires, think-aloud tests, interviews, and movement screening among 11 men aged 63 to 82 years with metastatic prostate cancer. Overall, 9 participants were undergoing androgen deprivation therapy, and 2 were completing chemotherapy. Data were collected in two waves, with changes made for quality improvement after participant 5. RESULTS: The intervention's usability score was deemed moderate overall but improved after modifications (from 60, SD 2.9 to 69.6, SD 2.2 out of 100). Overall, the participants found the intervention acceptable, with scores improving from wave 1 (24.2, SD 1.1 out of 30) to wave 2 (26.3, SD 2.1 out of 30). The personalized multimodal exercise prescription and computer-tailored education were seen as valuable. After wave 1, website navigation videos were added, medical terminology was simplified, and a telehealth component was included after expert real-time telehealth support was requested. Wave 2 changes included the added variety for aerobic exercise modes, reduced computer-tailoring question loads, and improved consistency of style and grammar. Finally, the participants could replicate the resistance exercise videos to a satisfactory level as judged by the movement screen; however, additional technique cueing within the videos is recommended to address safety concerns. CONCLUSIONS: The acceptability and usability of ExerciseGuide were deemed satisfactory. Various problems were identified and resolved. Notably, the participants requested the inclusion of personalized expert support through telehealth. The resistance training algorithms were shown to provide appropriate content safely, and the users could replicate the exercise technique unaided to a satisfactory level. This study has optimized the ExerciseGuide intervention for further investigation in this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001978257; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001978257.

Evaluating a web- and telephone-based personalised exercise intervention for individuals living with metastatic prostate cancer (ExerciseGuide): protocol for a pilot randomised controlled trial.

INTRODUCTION: Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. Despite this, many individuals do not engage in sufficient exercise to gain the benefits. There are many barriers, which limit the uptake of face-to-face exercise in this population including lack of suitable facilities, remoteness, and access to experts, significant fatigue, urinary incontinence and motivation. Technology-enabled interventions offer a distance-based alternative. This protocol describes a pilot two-armed randomised controlled study that will investigate the feasibility and preliminary efficacy of an online exercise and behavioural change tool (ExerciseGuide) amongst individuals with metastatic prostate cancer. METHODS: Sixty-six participants with histologically diagnosed metastatic prostate cancer will be randomised into either the 8-week intervention or a wait-list control. The intervention arm will have access to a tailored website, remote supervision, and tele-coaching sessions to enhance support and adherence. Algorithms will individually prescribe resistance and aerobic exercise based upon factors such as metastasis location, pain, fatigue, confidence and current exercise levels. Behavioural change strategies and education on exercise benefits, safety and lifestyle are also tailored through the website. The primary outcome will be intervention feasibility (safety, usability, acceptability, and adherence). Secondary exploratory outcomes include changes in physical activity, quality of life, sleep, and physical function. Outcomes will be measured at baseline and week 9. DISCUSSION: The study aims to determine the potential feasibility of an online remotely monitored exercise intervention developed for individuals with metastatic prostate cancer. If feasible, this pilot intervention will inform the design and implementation of further distance-based interventions. TRIAL REGISTRATION: ANZCTR, ACTRN12614001268639 . Registered 10 December 2018, https://anzctr.org.au/ACTRN12618001979246.aspx.

Technical Refinements in Superextended Robot-assisted Radical Prostatectomy for Locally Advanced Prostate Cancer Patients at Multiparametric Magnetic Resonance Imaging.

BACKGROUND: The feasibility and efficacy of robot-assisted radical prostatectomy (RARP) in locally advanced prostate cancer (PCa) patients with iT3 lesion at magnetic resonance imaging (MRI) are currently not explored. OBJECTIVE: To describe our revised RARP technique (ie, superextended RARP [SE-RARP]) for PCa patients with posterior iT3a or iT3b at MRI. DESIGN, SETTING, AND PARTICIPANTS: Data from 89 patients with posterior iT3a or T3b disease who underwent SE-RARP at a single high-volume centre between 2015 and 2018 were analysed. SURGICAL PROCEDURE: RARP was performed using a DaVinci Xi system. The surgical approach provided an inter- or extrafascial RARP where Denonvilliers' fascia and perirectal fat were dissected free and left on the posterior surface of the seminal vesicles. MEASUREMENTS: Perioperative outcomes, and intra- and postoperative complications were assessed. Postoperative outcomes were assessed in patients with complete follow-up data (n = 78). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable Cox regression models were used. RESULTS AND LIMITATIONS: The median operative time, blood loss, and length of stay were 204 min, 300 ml, and 5 d, respectively. The median bladder catheterisation time was 5 d. Overall, 28%, 28%, and 27% of patients had pathological grade group (GG) 4-5, pT3b, and positive surgical margins (PSMs), respectively. Three patients (3.4%) experienced intraoperative complications. Among patients with available follow-up data (n = 78), 14 (18%) experienced 30-d postoperative complications. The median follow-up was 19 mo. Overall, 11 patients received additional treatment. At 2 yr of follow-up, BCR-free and additional treatment-free survival were 55% and 66%, respectively. Pathological GG 4-5 (hazard ratio [HR] 3.2) and PSM (HR 5.8) were independent predictors of recurrence, as well as of additional treatment use (HR 5.6 for GG 4-5 and 5.2 for PSM). The 1-yr UC recovery was 84%. CONCLUSIONS: We presented our revised RARP technique applicable to patients with posterior iT3a or iT3b at preoperative MRI. This technique is associated with good morbidity and continence recovery rates, and might guarantee biochemical control of the disease and postpone the use of additional treatments in patients with low-grade and negative surgical margins. PATIENT SUMMARY: A revised robot-assisted radical prostatectomy technique applicable to prostate cancer patients with posterior iT3a or iT3b lesion at magnetic resonance imaging was described. This novel technique is feasible and safe in expert hands.

Examining the Priorities, Needs and Preferences of Men with Metastatic Prostate Cancer in Designing a Personalised eHealth Exercise Intervention.

BACKGROUND: Few individuals with metastatic prostate cancer have access to prostate cancer-specific exercise support, despite demonstrated benefits. eHealth tools, such as websites, may be viable options for increasing access. To be effective and acceptable, future eHealth websites need to consider end-users' perspectives, capacity and needs. We aim to provide insight into these factors by exploring daily priorities, activities and health literacy of individuals with metastatic prostate cancer and their perspectives towards exercise and exercise-based web-based eHealth interventions. METHODS: Semi-structured interviews explored participant's experiences and understanding of their disease, exercise levels, advice received from health care providers, as well as acceptability of and suggested content for an eHealth tool. A thematic analysis was undertaken. RESULTS: Interviews were conducted with eighteen Australians (55-83 years; M = 71.5, SD = 8.9) living with metastatic prostate cancer. Needing to perform daily responsibilities was a key priority. Participants had limited understanding of the benefits of prostate cancer-specific exercise, and less than half discussed exercise with their health team. Fourteen men felt they could report metastases location, but only four could provide detailed information, which has clinical implications for exercise prescription. A potential web-based intervention was considered acceptable by seventeen men for reasons such as affordability, accessibility and convenience. User-friendly design and practitioner support were important. CONCLUSIONS: Results identified key aspects useful for person-centred design of exercise programs. Participants were positive towards the proposed web-based tool and expressed the need for individualised, user-friendly and reliable information with support from a professional embedded. Lastly, not all participants could accurately report metastasis locations.

Comprehensive training in robotic surgery.

PURPOSE OF REVIEW: Robotic training in urology can be poorly structured, lack a basic skills foundation, and may not include teaching in important nontechnical human factor skills vital to the safe delivery of robotic care. Assessment of acquired skills is not routine. There is a need for structured and standardized curricular to deliver validated training and final assessment. The present reviews the current literature on training methods for robotic surgery, and examines the evidence for their effect on performance, where available. RECENT FINDINGS: There is good evidence for the beneficial effect of dry lab simulators on robotic skills acquisition, but less for cadaveric and animal models. Two urological authorities have developed comprehensive curricula for robotic training that take a novice robotic surgeon through the full stages of robotic skills acquisition. These are in the early stages of development and validation but have stimulated the development of curricula in other specialties. SUMMARY: The future landscape for robotic urology training is likely to include structured, mandated, and centralized training, possibly administered by urological organizations. There will be roles for telementoring, advanced education for robotic trainers, and regular revalidation of expert robotic surgeons.

TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

The Importance of Technical and Non-technical Skills in Robotic Surgery Training.

We discuss the differences in cognitive (thinking) and other non-technical skills (NTS) in robotic surgery training compared to other approaches to surgery. Recognition of the importance of NTS and cognitive training will aid the development of robotic surgery curricula.

Disseminated Intravascular Coagulation After Embolization to Treat Acutely Bleeding Bilateral Massive Angiomyolipoma: A Case Report.

Background: Hemorrhage from an angiomyolipoma (AML) of the kidney can be life threatening and arterial embolization is the primary treatment. Embolization is less invasive than surgery, is well tolerated, and major complications are rare. We describe a case of disseminated intravascular coagulation (DIC) after embolization of a bleeding renal AML in a 44-year-old man with massive bilateral AMLs. This report aims to highlight the possibility that acute DIC could be a major complication of embolization itself and so should be considered and screened for because, if present, it requires early and aggressive management. Case Presentation: A 44-year-old man with a history of large bilateral renal AMLs associated with tuberous sclerosis complex presented with visible hematuria and abdominal pain. Renal CT revealed bleeding from the right kidney. Embolization with polyvinyl alcohol and lipiodol was urgently performed. The following day he required multiple blood transfusions and repeat embolization, this time with gelfoam and "tornado" coils. He suddenly developed DIC, cardiovascular collapse and acute renal failure requiring many days in the intensive care unit for inotropic support and renal replacement therapy. Conclusion: Arterial embolization may be associated with increased risk of DIC in the setting of treating large bleeding renal AMLs. DIC may be a direct or indirect complication of this. The clinician must act quickly to identify this and treat this complication aggressively.

Erectile dysfunction is independently associated with apnea-hypopnea index and oxygen desaturation index in elderly, but not younger, community-dwelling men.

OBJECTIVE(S): To examine the association between obstructive sleep apnea (OSA) and other sleep indices using polysomnography (PSG) data and erectile dysfunction (ED) in a representative cohort of men. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: Aged 40+ years (n=734; mean age [SD], 60.8 [10.9]). MEASUREMENTS: Men with no prior OSA diagnosis who underwent in-home PSG (Embletta X100; 2010-11) and ED assessment (Global Impotence Rating) were selected. Un-adjusted and multi-adjusted regression models of ED were fitted against PSG measures, along with qualifying sociodemographic, lifestyle, and health-related covariates. Mediation effects were examined using the Baron-Kenny method. RESULTS: Of the men examined, 24.7% (n=181) had ED, most notably in men older than 65years (cf. men 35-49 and 50-64years; P<.001). There was no significant association between ED and any of the PSG measures for allaged men. Given an observed ageinteraction within OSA categories (P=.005), analyses were repeated in age-stratified samples (<65 years; 65+ years). In men younger than 65years, only severe OSA was found to have an association with ED (2.01; 1.13-4.69) in unadjusted models. For men aged 65+ years, an independent association with ED was found for apnea-hyponea index (AHI; 1.55;1.02-2.36), moderate (AHI:10.0-19.9; 1.79;1.18-2.43), and severe (AHI:20.0+; 4.84;2.56-9.93) OSA, and oxygen desaturation index (ODI; both continuous [1.48;1.03-1.99] and >16 seconds [2.79;1.23-6.32]). The effect of AHI on ED was shown to be primarily mediated through ODI (63.4%, Sobel P value=.29). CONCLUSIONS: In younger, community-based men, there appeared no independent relationship between objective measures of sleep and ED. However, there appears a strong, independent relationship between OSA, ODI, and ED in men 65 years and older.

Identifying predictors of change in the severity of untreated lower urinary tract symptoms in men: a systematic review protocol.

REVIEW OBJECTIVE: The objective of this systematic review is to synthesize the best available evidence on the predictors of change in the severity of untreated lower urinary tract symptoms in men in a non-hospital setting.

High-grade transitional cell carcinoma masquerading as a xanthogranulomatous pyelonephritis and perinephric abscess.

Xanthogranulomatous pyelonephritis (XGPN) is an atypical long-term pyelonephritis with destruction of renal parenchyma and a long-term inflammatory infiltrate of macrophages. Reported presentations of transitional cell carcinoma (TCC) are different. A 73-year-old woman presented with loin pain, prostration, and fever. Computed tomography scan revealed poor cortical enhancement of the kidney, but some of the images bore resemblance to the characteristic "bear's paw" sign, consistent with XGPN with a 7-cm perinephric collection. She was provisionally diagnosed as severe acute pyelonephritis, possibly XGPN, with abscess. In view of the poor clinical condition, decision was made to perform nephrectomy. Histology revealed a G3pT4 high grade TCC with perineural and vascular invasion and reactive xanthogranulomatous inflammatory response. There are few reports of concomitant XGPN and TCC affecting the kidney. However, there has not been any mention of XGPN and TCC presenting as acute pyelonephritis and perinephric abscess so far.

Intravesical Bacillus Calmette-Guérin with interferon-alpha versus intravesical Bacillus Calmette-Guérin for treating non-muscle-invasive bladder cancer.

BACKGROUND: Despite local therapies, commonly transurethral resection (TUR) followed by adjuvant treatments, non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence and progression. Intravesical Bacillus Calmette-Guérin (BCG) has been shown to reduce recurrence and progression in people with NMIBC following TUR, however many people do not respond to treatment, have recurrence shortly after, or cannot tolerate standard-dose therapy. The potential for synergistic antitumour activity of interferon (IFN)-alpha (α) and BCG provides some rationale for combination therapy for people who do not tolerate or respond to standard-dose BCG therapy. OBJECTIVES: To assess the effects of intravesically administered BCG plus IFN-α compared with BCG alone for treating non-muscle-invasive bladder cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2016), MEDLINE (OvidSP) (1946 to 2016), Embase (OvidSP) (1974 to 2016), ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) as well as reference lists of retrieved articles and handsearched abstract proceedings of relevant conferences for the past three years. We applied no language restrictions. The date of last search of all databases was 25 August 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and pseudo-randomised trials assessing intravesically administered BCG plus IFN-α versus BCG alone in adults of either gender with histologically confirmed Ta and T1 superficial bladder cancer, with or without carcinoma in situ, treated with TUR. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We used Review Manager 5 for data synthesis and employed the random-effects model for meta-analyses. For prespecified outcomes, where we were unable to derive time-to-event information (e.g. time-to-recurrence), we assessed dichotomous outcomes (e.g. recurrence) instead. We assessed the quality of the evidence for the main comparisons using the GRADE approach. MAIN RESULTS: We included five RCTs involving a total of 1231 participants with NMIBC in this review. Due to poor reporting, the risk of bias in the included studies was often unclear. We assessed the studies under two main comparisons: intravesical BCG plus IFN-α versus intravesical BCG alone (four RCTs), and intravesical BCG alternating with IFN-α versus intravesical BCG alone (one RCT). Intravesical BCG plus IFN-α versus intravesical BCG alone (four RCTs): We observed no clear difference between BCG plus IFN-α and BCG alone for recurrence (average risk ratio (RR) 0.76, 95% confidence interval (CI) 0.44 to 1.32; 4 RCTs; 925 participants; very low-quality evidence) or progression (average RR 0.26, 95% CI 0.04 to 1.87; 2 RCTs; 219 participants; low-quality evidence). The included RCTs did not report on the other primary outcome of this review, discontinuation of therapy due to adverse events. Regarding secondary outcomes, we observed no clear difference for disease-specific mortality (RR 0.38, 95% CI 0.05 to 3.05; 1 RCT; 99 participants; very low-quality evidence). Two RCTs reporting contradictory findings for adverse events could not be pooled due to variation in definitions. There were no data from the included RCTs on time-to-death or disease-specific quality of life. Intravesical BCG alternating with IFN-α versus intravesical BCG alone (one RCT): We observed shorter time-to-recurrence for participants in the BCG alternating with IFN-α group compared with the BCG alone group (hazard ratio (HR) 2.86, 95% CI 1.98 to 4.13; 1 RCT; 205 participants; low-quality evidence), but no clear differences in time-to-progression (HR 2.39, 95% CI 0.92 to 6.21; 1 RCT; 205 participants; low-quality evidence) and discontinuation of therapy due to adverse events (RR 2.97, 95% CI 0.31 to 28.09; 1 RCT; 205 participants; low-quality evidence). Regarding secondary outcomes, there were no clear differences between the BCG alternating with IFN-α and BCG alone groups for disease-specific mortality (HR 2.74, 95% CI 0.73 to 10.28; 1 RCT; 205 participants; low-quality evidence), time-to-death (overall survival) (HR 1.00, 95% CI 0.68 to 1.47; 1 RCT; 205 participants; low-quality evidence), or systemic or local adverse events (RR 1.65, 95% CI 0.41 to 6.73; 1 RCT; 205 participants; low-quality evidence). There were no data on disease-specific quality of life. AUTHORS' CONCLUSIONS: We found low- to very low-quality evidence suggesting no clear differences in recurrence or progression with BCG plus IFN-α compared with BCG alone for people with NMIBC; there was no information to determine the effect on discontinuation of therapy due to adverse events. Low-quality evidence suggests BCG alternating with IFN-α compared with BCG alone may increase time-to-recurrence, however low-quality evidence also suggests no clear differences for time-to-progression or discontinuation of therapy due to adverse events.Additional high-quality, adequately powered trials using standardised instillation regimens and doses of both BCG and IFN-α, reporting outcomes in subgroups stratified by patient and tumour characteristics, and on long-term outcomes related not only to recurrence but also to progression, discontinuation due to adverse events, and mortality may help to clarify the ideal treatment strategy and provide a more definitive result.

Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial.

OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.

Ureteroiliac Artery Fistula Caused by a Metallic Memokath Ureteral Stent in a Radiation-Induced Ureteral Stricture.

Background: Memokath 051™ stents are increasingly used for management of benign and malignant ureteral strictures refractory to management with single or tandem polymeric Double-J ureteral stents. Migration, encrustation, and difficulty in extraction during stent exchange are the chief problems reported so far with these thermoexpandable metallic stents. We report an unusual complication of ureteroexternal iliac artery fistula (UEAF) caused by Memokath stent inserted for radiation-induced ureteral stricture. Case Presentation: A 71-year-old male with history of colorectal cancer (underwent extirpative surgery + chemoradiotherapy) and subsequently radiation-induced ureteral stricture had bilateral Memokath ureteral stents inserted. Three months later, he presented with sepsis and hemodynamic instability secondary to UEAF, confirmed on angiography. A covered vascular stent was inserted as an immediate management. Conclusion: Memokath stent insertion in radiation-induced ureteral strictures may be associated with an increased risk of erosion and the rare potential complication of UEAF. This potential risk needs to be considered in the overall setting of such strictures and the difficulty in treating them. Prompt imaging (angiography) and placement of an endovascular stent are the ideal immediate options in such cases.