Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations.

BACKGROUND: There is currently limited literature assessing the real-world treatment patterns and clinical outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) mutations. METHODS: Medical charts were abstracted for mCRPC patients with ≥ 1 of 12 HRR somatic gene alterations treated at US oncology centers participating in the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange. Treatment patterns and clinical outcomes were assessed from the initiation of first-line or later (1L+) mCRPC therapy received on or after July 1, 2014. RESULTS: Among 138 patients included in the study, the most common somatic HRR mutations were CDK12 (47.8%), BRCA2 (22.5%), and ATM (21.0%). Novel hormonal therapy and taxane chemotherapy were most commonly used in 1L; taxane use increased in later lines. Median overall survival (95% confidence interval [CI]) was 36.3 (30.7-47.8) months from initiation of 1L therapy and decreased for subsequent lines. Similarly, there was a trend of decreasing progression-free survival and prostate-specific antigen response from 1L to 4L+ therapy. CONCLUSIONS: Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

Preoperative three-dimensional modelling and virtual reality planning aids nephron sparing surgery in a child with bilateral Wilms tumour.

Bilateral Wilms tumour (BWT) is a surgically challenging condition. Virtual reality (VR) reconstruction aids surgeons to foresee the anatomy ahead of Nephron Sparing Surgery (NSS). Three-dimensional (3D) visualisation improves the anatomical orientation of surgeons performing NSS. We herewith report a case of BWT where VR planning and 3D printing were used to aid NSS. Conventional imaging is often found to be inadequate while assessing the tumour-organ-vascular anatomy. Advances like VR and 3D printing help surgeons plan better for complex surgeries like bilateral NSS. Next-generation extended reality tools will likely aid robotic-assisted precision NSS and improve patient outcomes.

A review for the impacts of circadian disturbance on urological cancers.

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

True mesothelial cyst of the adrenal gland: its clinical profile and management.

The incidence of adrenal cysts is 0.06% and only 9% of these are true mesothelial cysts. Here, we present a case of a true mesothelial cyst together with a review of the literature. A female in her 30s presented to the surgical outpatient department complaining of right flank pain. Her contrast-enhanced CT scan revealed a 7.5×6.5×4.5 cm right adrenal gland cyst. The patient underwent a laparoscopic right adrenalectomy. Immunohistopathology revealed the cyst to be mesothelial in nature. The majority of true mesothelial adrenal cysts are benign, unilateral and more common in women. Any adrenal cyst diagnosed as a functional lesion or one that may be malignant or with a diameter of 5 cm or greater requires surgical care whereas smaller lesions can be managed conservatively. Laparoscopic adrenalectomy for an adrenal cyst of diameter greater than 6 cm is a safe and feasible procedure in expert hands if there is no invasion of surrounding tissue.

Management conundrum in a case of renal cell cancer (RCC) on dual antiplatelet therapy (DAPT) for recently placed coronary drug-eluting stent (DES).

A man in his 50s presented in an emergency with breathlessness and chest discomfort. On evaluation, he was diagnosed with coronary artery disease, with more than 80% narrowing of the right coronary and left circumflex arteries. The patient underwent percutaneous coronary intervention and was started on dual antiplatelet (DAPT) therapy. After starting DAPT, the patient developed gross haematuria with a drop in haematocrit. Further evaluation revealed a left renal mass with urinary bladder clots. Because of the risk of stent thrombosis on stopping DAPT, radical nephrectomy was deferred, and the patient underwent left renal artery angioembolisation and bladder clot evacuation. On the follow-up, the patient was stable with a gradual decrease in renal mass size, and after a year, the patient underwent definitive surgery. The patient is doing well in 4 years of follow-up with no metastasis.

The National Health Service urgent cancer referral pathway for suspected urological cancers: early economic evaluation of a risk prediction test.

OBJECTIVES: In the UK, the number of patients urgently referred for suspected cancer is increasing, and providers are struggling to cope with demand. We explore the potential cost-effectiveness of a new risk prediction test - the PinPoint test - to triage and prioritize patients urgently referred with suspected urological cancers. METHODS: Two simulation models were developed to reflect the diagnostic pathways for patients with (i) suspected prostate cancer, and (ii) bladder or kidney cancer, comparing the PinPoint test to current practice. An early economic analysis was conducted from a UK National Health Service (NHS) perspective. The primary outcomes were the percentage of individuals seen within 2 weeks and health care costs. An exploratory analysis was conducted to understand the potential impact of the Pinpoint test on quality-adjusted life years gained. RESULTS: Across both models and applications, the PinPoint test led to more individuals with urological cancer being seen within 2 weeks. Using PinPoint only to prioritize patients led to increased costs overall, whereas using PinPoint to both triage and prioritize patients led to cost savings. The estimated impact on life years gained/lost was very small and highly uncertain. CONCLUSIONS: Using the PinPoint test to prioritize urgent referrals meant that more individuals with urological cancer were seen within 2 weeks, but at additional cost to the NHS. If used as a triage and prioritization tool, the PinPoint test shortens wait times for referred individuals and is cost saving. More data on the impact of short-term delays to diagnosis on health-related quality of life is needed.

Renal cell carcinoma (RCC) spreading to the larynx: an unusual condition.

A man in his mid-70s, heavy smoker with chronic alcohol consumption and a chronic exposure to insecticides and burning of crop residues was referred to the surgical oncology department because of a 4-month onset of hoarseness, dyspnoea and laryngeal stridor. He had a history of left nephrectomy due to Fuhrman IV clear cell renal cancer 2 years ago. The patient underwent a bronchoscopy which identified a deforming tumour of the left vallecula, occlusion of 90% of the lumen and did not allow a safe biopsy. Following discussion between the oncological team, total laryngectomy and bilateral neck dissection of levels II, III, IV and V were performed, finding a transglottic tumour of approximately 4×3 cm with extension to the right anterolateral thyroid cartilage. The pathology report described metastatic RCC. The patient recovered well postoperatively and started systemic therapy with a vascular endothelial growth factor receptors inhibitor.

Postradical cystectomy delayed urethral recurrence: a rare presentation posing diagnostic dilemma.

The incidence of urethral recurrence after radical cystectomy is 1% to 8%, with most cases occurring within the first 2 years of surgery. Prophylactic urethrectomy is rarely performed nowadays due to no known survival benefit and increased morbidity due to the procedure. However, we encountered a rare case of delayed urethral recurrence presenting as recurrent urethral collection 4 years after radical cystectomy with ileal conduit diversion, posing a diagnostic dilemma.

Small cell bladder carcinoma treated with nivolumab as adjuvant maintenance therapy.

We report using the programmed death-1 immune checkpoint inhibitor (ICI) antibody, nivolumab, as part of a multimodal treatment strategy in small cell bladder carcinoma (SCBC). The patient presented with gross haematuria and was diagnosed with urothelial carcinoma with SCBC. He received neoadjuvant chemotherapy (NAC; carboplatin plus etoposide) according to the small cell lung cancer regimen. After three cycles of NAC, there was no progression of local disease, and a robot-assisted radical cystectomy with ileal conduit was conducted. Post surgery, the patient was treated with nivolumab (240 mg) every 2 weeks as a maintenance therapy after adjuvant cisplatin plus etoposide therapy. After more than 1.5 years post surgery, no tumour recurrence or metastases are present. The patient was treated with nivolumab, which was curative after radical cystectomy. Further research is required to elucidate the potential role of ICIs in SCBC.

Regressed Non-metastatic Germ Cell Tumour: A Case Report and Literature Review.

Testicular germ cell tumour regression is a rare phenomenon, where the primary testicular tumour spontaneously regresses, typically with metastatic disease at presentation. We present a case of a regressed germ cell tumour (GCT) in a 44-year-old post-pubertal male. Initially treated for suspected infection, the patient's testicular swelling prompted further investigation, leading to a radical orchidectomy that revealed the unusual histomorphologic findings of an entirely necrotic, non-seminomatous GCT consistent with a pure embryonal carcinoma.

Therapeutic Effects of Berberine against Urological Cancers: Biological Potentials Based on Cellular Mechanisms.

Urological cancers, including prostate, kidney, and bladder cancer are problematic human diseases worldwide. Current strategies for the treatment of these cancers are chemotherapy, radiotherapy, surgery, or a combination of mentioned therapies. Due to the high mortality and morbidity rate of urological cancers and possible side effects of available standard treatments, searching for more effective and safe treatments is a critical issue. The beneficial properties of natural compounds, such as berberine, have been widely investigated in human diseases. Moreover, the anticancer potential of this agent has been extensively documented, especially in experimental studies. In this review, we have tried to discuss the effect of berberine against urological cancers, focusing on cellular and molecular mechanisms.

Prognostic value of preoperative albumin-to-alkaline phosphatase ratio in patients with surgically treated urological cancer: a systematic review and meta-analysis.

Objective: A novel albumin-to-alkaline phosphatase ratio (AAPR) is associated with the prognosis of several cancers. In the present study, we evaluate the prognostic significance of perioperative AAPR in urological cancers. Method: Relevant studies were searched comprehensively from CNKI, PubMed, Embase and Web of Science up to March 2023. The pooled hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study to evaluate the prognostic value of perioperative AAPR in patients with surgically treated urological cancers. Results: A total of 8 studies consisting of 3,271 patients were included in the final results. A low AAPR was significantly associated with a worse OS (HR=2.21; P<0.001), CSS (HR=2.61; P<0.001) and RFS/DFS (HR=2.87; P=0.001). Stratified by disease, a low AAPR was also associated with worse OS in renal cell carcinoma (HR=2.01; P<0.001), bladder cancer (HR=3.37; P<0.001) and upper tract urothelial carcinoma (HR=1.59; P=0.002). Conclusion: In conclusion, low AAPR could serve as an unfavorable factor in patients with surgically treated urological cancers. Stratified by tumor type, the low AAPR was also associated with inferior survival. While more prospective and large-scale studies are warranted to validate our findings.

The current landscape of m6A modification in urological cancers.

N6-methyladenosine (m6A) methylation is a dynamic and reversible procession of epigenetic modifications. It is increasingly recognized that m6A modification has been involved in the tumorigenesis, development, and progression of urological tumors. Emerging research explored the role of m6A modification in urological cancer. In this review, we will summarize the relationship between m6A modification, renal cell carcinoma, bladder cancer, and prostate cancer, and discover the biological function of m6A regulators in tumor cells. We will also discuss the possible mechanism and future application value used as a potential biomarker or therapeutic target to benefit patients with urological cancers.

Pedal acrometastasis secondary to urothelial carcinoma masquerading as Charcot arthropathy in a patient with diabetes.

A woman in her 80s with known diabetes mellitus and bladder cancer presented to her general practitioner (GP) with pain and swelling in her left foot following trauma. Initial radiographs were reported as normal, prompting a diagnosis of a simple sprain and conservative management. Three months later, the patient was referred to the orthopaedic team due to progressively increasing pain and swelling. Repeat X-rays revealed lytic lesions in both the talus and navicular bones; MRI confirmed the presence of a lytic and proliferative defect in the mid-foot, which was reported as acute Charcot arthropathy with superimposed infection. This was also considered the most likely diagnosis when imaging was reviewed in two separate multidisciplinary team) meetings. However, biopsy demonstrated that the cause of the presentation was in fact acrometastasis from urothelial carcinoma, an infrequently described entity.

A Large Genetic Causal Analysis of the Gut Microbiota and Urological Cancers: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Several observational studies and clinical trials have shown that the gut microbiota is associated with urological cancers. However, the causal relationship between gut microbiota and urological cancers remains to be elucidated due to many confounding factors. METHODS: In this study, we used two thresholds to identify gut microbiota GWAS from the MiBioGen consortium and obtained data for five urological cancers from the UK biobank and Finngen consortium, respectively. We then performed a two-sample Mendelian randomization (MR) analysis with Wald ratio or inverse variance weighted as the main method. We also performed comprehensive sensitivity analyses to verify the robustness of the results. In addition, we performed a reverse MR analysis to examine the direction of causality. RESULTS: Our study found that family Rikenellaceae, genus Allisonella, genus Lachnospiraceae UCG001, genus Oscillibacter, genus Eubacterium coprostanoligenes group, genus Eubacterium ruminantium group, genus Ruminococcaceae UCG013, and genus Senegalimassilia were related to bladder cancer; genus Ruminococcus torques group, genus Oscillibacter, genus Barnesiella, genus Butyricicoccus, and genus Ruminococcaceae UCG005 were related to prostate cancer; class Alphaproteobacteria, class Bacilli, family Family XI, genus Coprococcus2, genus Intestinimonas, genus Lachnoclostridium, genus Lactococcus, genus Ruminococcus torques group, and genus Eubacterium brachy group were related to renal cell cancer; family Clostridiaceae 1, family Christensenellaceae, genus Eubacterium coprostanoligenes group, genus Clostridium sensu stricto 1, and genus Eubacterium eligens group were related to renal pelvis cancer; family Peptostreptococcaceae, genus Romboutsia, and genus Subdoligranulum were related to testicular cancer. Comprehensive sensitivity analyses proved that our results were reliable. CONCLUSIONS: Our study confirms the role of specific gut microbial taxa on urological cancers, explores the mechanism of gut microbiota on urological cancers from a macroscopic level, provides potential targets for the screening and treatment of urological cancers, and is dedicated to providing new ideas for clinical research.

Paraneoplastic sacroiliitis.

A man in his early 70s presented with stiffness and aching in the shoulder and pelvic girdles. His C reactive protein level was elevated at 116 mg/L, leading to an initial diagnosis of polymyalgia rheumatica. Treatment with prednisone at 20 mg/day provided limited improvement and relapses recurred despite concomitant immunosuppressive agents. Extensive investigations failed to reveal an underlying aetiology.Five years later, gross painless haematuria led to the detection of an invasive papillary urothelial carcinoma. A review of the staging CT scan revealed findings compatible with bilateral erosive sacroiliitis, which had developed since his initial presentation. Radical cystoprostatectomy provided temporary relief but after a further 9 months, symptoms relapsed, and metastatic spread was discovered.Paraneoplastic sacroiliitis is a rare clinical entity; and to the best of our knowledge, this is the first reported case associated with a solid tumour.

Cryoablation following neoadjuvant tyrosine kinase inhibitor as treatment of a T1a renal clear cell carcinoma in a patient with a solitary kidney.

The case is presented of a woman in her 60s with renal cell carcinoma in a solitary kidney with normal renal function. Because of the solitary kidney status, the management strategy described in acknowledged guidelines was not possible. The patient was treated with standard first-line tyrosine kinase inhibitor followed by percutaneous CT-guided cryoablation. Before and after the procedure the patient had normal kidney function. The treatment resulted in local cancer control, but a bone metastasis developed in the thoracic part of the spine.

The Present and Future of Artificial Intelligence in Urological Cancer.

Artificial intelligence has drawn more and more attention for both research and application in the field of medicine. It has considerable potential for urological cancer detection, therapy, and prognosis prediction due to its ability to choose features in data to complete a particular task autonomously. Although the clinical application of AI is still immature and faces drawbacks such as insufficient data and a lack of prospective clinical trials, AI will play an essential role in individualization and the whole management of cancers as research progresses. In this review, we summarize the applications and studies of AI in major urological cancers, including tumor diagnosis, treatment, and prognosis prediction. Moreover, we discuss the current challenges and future applications of AI.

The PRO-RCC study: a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for 'Trial within Cohorts' study designs.

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs). METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician. TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620). DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.