The role of URO17® in diagnosis and follow up of bladder cancer patients.

OBJECTIVE: to evaluate the role of urinary URO17® biomarker in the detection of urothelial tumors in haematuria patients and the detection of recurrence in non-muscle invasive bladder urothelial tumors. MATERIALS AND METHODS: Our study was formed of two cohorts of patients, group I represents patients presenting with haematuria (n = 98), while group II represents patients with known non-muscle invasive bladder cancers on their scheduled follow up cystoscopic investigation (n = 51). For both groups, patients were asked to provide urine samples before cystoscopy, either primary as part of the haematuria investigation or as a scheduled follow-up. Urine samples were sent anonymously for standard urine cytology and URO17® biomarker immunostaining. Results were compared to cystoscopic findings using Chi-square analysis and Fisher's exact test (P < 0.05). RESULTS: Group I was formed of 98 patients, with an average age of 60 years. URO17® showed 100% sensitivity and 96.15% specificity with a negative predictive value (NPV) of 100 and a positive predictive value (PPV) of 95.83. The results showed statistical significance with P value < 0.001. Group II was formed of 51 patients, with an average age of 75 years. URO17® was shown to have a sensitivity of 85.71% and NPV of 95.45. Eleven patients of group II were on scheduled BacillusCalmette-Guerin (BCG) and another 5 received Mitomycin C (MMC). The overall results of both groups combined (n = 149) showed statistical significance between flexible cystoscopy results and the results of urinary URO17® and urine cytology. CONCLUSION: URO17® has a potential to be a reliable test for diagnosis and follow up of urothelial cancer patients and a screening tool adjunct to flexible cystoscopy. TRIAL REGISTRATION: Not applicable as the current study is not a clinical trial, as per according to the National Institutes of Health, "studies that involve a comparison of methods and that do not evaluate the effect of the interventions on the participant do not meet the NIH clinical trial definition."

A North-West London Experience of the Impact of Treatment Related Toxicity on Clinical Outcomes of Elderly Patients with Germ Cell Tumors.

Background/Aim: The occurrence of germ cell tumour (GCT) in the elderly is rare, with scarce data available. The aim of this study was to understand the clinical outcomes of patients with GCT in patients aged > 45 years. Materials and Methods: A retrospective study was conducted in a large tertiary cancer centre in north-west London. Between 1 January 2003 and 31 March 2022, 108 cases of GCT in men aged > 45 years were identified and treated at the Mount Vernon Cancer Centre. The median age at diagnosis was 54 years (range = 45−70 years). Results: The 5-year survival rate of all patients was 96%, and the toxicity profile was similar to the younger age group. Conclusion: Older patients with GCT are able to tolerate chemotherapy; however, care must be taken to prevent life-threatening complications using appropriate dose modification.

Single-agent carboplatin AUC10 in metastatic seminoma: A multi-centre UK study of 216 patients.

BACKGROUND: Radiotherapy and cisplatin-based combination chemotherapy are accepted standard-of-care treatments for metastatic seminoma with excellent survival outcomes but with established short- and long-term morbidity. Carboplatin monotherapy may be a less toxic alternative; however early historic studies at AUC7 showed inferior outcomes. OBJECTIVES: To evaluate multi-institutional data on and toxicity and longer-term survival for metastatic seminoma patients treated with the single-agent carboplatin AUC10. METHODS: We undertook a multi-institutional analysis incorporating all men with the International Germ Cell Cancer Collaborative Group good-prognosis metastatic seminoma treated until 2018. Carboplatin AUC10 was given every 21 days. Toxicity, progression-free survival (PFS), disease-specific survival (DSS) and overall survival were noted. Variables predictive of progression were identified. RESULTS AND LIMITATIONS: 216 patients were treated. The three-year PFS rate was 96.5%, and five-year DSS was 98.3%. There were seven relapses, of which 5 were successfully salvaged with further chemotherapy ± surgery, and three non-seminoma-related deaths. There were no treatment-related deaths. Of 148/216 evaluable patients for toxicity, 37% and 27% suffered >/ = grade III neutropenia and thrombocytopenia, respectively. Twelve percent of patients needed a platelet or blood transfusion (or both). The incidence of febrile neutropenia was 5%. CONCLUSION: For metastatic seminoma, carboplatin AUC10 harbours a similar oncological efficacy to established therapies, with a low failure risk. The major acute toxicity was myelosuppression. Our study establishes carboplatin AUC10 as another standard-of-care treatment option for good-prognosis metastatic seminoma, with a potentially lower toxicity profile than other therapies.

Neurovascular structure-adjacent frozen-section examination robotic-assisted radical prostatectomy: outcomes from 500 consecutive cases in the UK.

The purpose is to report the United Kingdom's largest single-centre experience of robotically assisted laparoscopic radical prostatectomies (RALP), using the neurovascular structure-adjacent frozen-section (NeuroSAFE) technique. We describe the utilisation and outcomes of this technique. This is a retrospective study from 2012 to 2019 on 520 patients undergoing NeuroSAFE RALP at our Institution. Our Institution's database was analysed for false-positive frozen-section (FS) margins as confirmed on paraffin histopathological analysis: functional outcomes of potency, continence, and biochemical recurrence (BCR). The median (range) of console time was 145 (90-300) min. In our cohort, positive FS was seen in 30.7% (160/520) of patients, with a confirmatory paraffin analysis in 91.8% of our patients' cohort (147/160). The neurovascular bundles (NVBs) that underwent secondary resection contained tumour in 26.8% (43/160) of the cases. Biochemical recurrence (BCR) was 6.7% (35/520), of which FS was positive in 40% (14/35) of those cases. There were insufficient evidence of a statistical association of urinary incontinence and positive surgical margin rates according to NS or NVB resection. NeuroSAFE enables intraoperative confirmation of the oncologic safety of a NS procedure. Patients with a positive FS on NeuroSAFE can be converted to a negative surgical margin (NSM) by ipsilateral wide resection. This spared 1 in 4 men from positive margins posterolaterally in our series. Limitations are the absence of a matched contemporary cohort of NS RALP without NeuroSAFE in our centre.

Secondary neoplasms of the urinary bladder-clinical management and oncological outcomes.

BACKGROUND: Secondary neoplasms of the bladder account for 4.5% of all bladder neoplasms however there is limited literature reporting management and survival. This is the largest single centre series presented in current literature with long term oncological follow up. METHODS: This is a single institutional, retrospective cohort study of patients with a histological diagnosis of a secondary bladder neoplasm from January 2007 to December 2017 (n=40). Prognostic variables examined included age at diagnosis, histology, disease free survival and treatment. Kaplan-Meier analysis was used to calculate survival. We used multiple regression analysis to identify the most significant treatments for each population group in terms of their survival. RESULTS: Twenty-one patients were male (53%) with a median age of 68 and 19 were female (47%) with a median age of 64. The most common secondary neoplasms and their median survival were prostate [12 patients (30%), 446 days], colorectal [9 patients (23%), 403 days], ovarian [5 patients (13%), 369 days], cervical [4 patients (10%), 148 days], breast [3 patients (8%), 241 days], lymphoma [3 patients (8%), 145 days], gastric [2 patients (5%), 66 days], and renal [2 patients (5%), 854 days]. Those receiving treatment following a secondary diagnosis demonstrated statistical significance in survival for colorectal (surgery P=0.013), prostate (radiotherapy P=0.0012 and hormonal therapy P=0.004) and ovarian cancer (chemotherapy P=0.00002). CONCLUSIONS: Prognosis and treatment depends upon the primary neoplasm. There is some survival benefit in well selected patients receiving treatment following a diagnosis of a bladder secondary.

The role of URO17™ biomarker to enhance diagnosis of urothelial cancer in new hematuria patients-First European Data.

Introduction and objectives: Novel biomarker research is vital for the progression of safe and thorough diagnostic medicine. There is now a need to improve the diagnosis of bladder cancer via a noninvasive urine test while balancing the risks of harm from investigational procedures, such as cystoscopy and radiological tests, against the likelihood of malignancy. We evaluate the diagnostic accuracy and sensitivity of Uro17™ urinary biomarker for the detection of urothelial cancer in hematuria patients in a prospective blinded validation study. Uro17™ is an immunobiomarker which binds to the oncoprotein Keratin 17, which is involved in the replication cycle of malignant cells. This study compared cystoscopic and histological investigations against Uro17™ results in patients being investigated for symptoms of urothelial cancer. Materials and methods: After receiving both local and national ethics/protocol approval, 71 patients were consented and recruited into the study. All patients were scheduled to undergo cystoscopic investigation, and following recruitment, a urine sample was collected. Urine samples were anonymized and processed as per standard cytology protocols and stained using Uro17™ immunobiomarker. The pathologists assessing the results were blinded to the patient and background history, and the results were compared to the biopsy histology. Results: The full cohort of enrolled patients consisted of 71 participants included. There were 55 males and 16 females, with an average age of 70. Thirteen were current smokers, 42 ex-smokers, and 16 nonsmokers. The malignancies detected included both muscle-invasive (n = 6) and non-muscle-invasive tumors (n = 38), and tumors of all grades and carcinoma in situ. Uro17™ was shown to have an overall sensitivity of 100% and a specificity of 92.6%, with a positive predictive value of 0.957 and negative predictive value of 1. Uro17™ investigation was positive in every case of urothelial malignancy. Conclusions: Our current data indicates Uro17™ is a highly sensitive noninvasive bladder cancer urine detection test that can improve the diagnosis of Bladder cancer. This can further improve diagnostic capabilities in primary care, reduce the number of referrals to Urology department, and reduce the number of unnecessary invasive procedures for new patients with a suspected urinary bladder cancer.

Incidental Lymphoplasmacytic Lymphoma Diagnosed Following Robotic-Assisted Laparoscopic Prostatectomy for Prostate Cancer.

We report a case of prostatic lymphoma of the Walden-ström's macroglobulinemia subtype in a 64-year-old gentleman who underwent a robotic-assisted laparoscopic prostatectomy following lower urinary tract symptoms and high grade adenocarcinoma on transperineal prostate biopsy's. Histopathological and immunohistochemistry analysis at the time of surgery was consistent with a CD5-negative small B-cell lymphoma. To our knowledge this is the first reported prostatic lymphoma identified following robotic-assisted laparoscopic prostatectomy and the first documented case of lymphoplasmacytic lymphoma involving prostate. Lymphoma of the prostate is an uncommon entity in surgical practice and their diagnosis often poses considerable difficulty as they often mimic carcinoma. We discuss this rare diagnosis and review the literature for current considerations and prognosis.

The neurovascular structure-adjacent frozen-section examination (NeuroSAFE) approach to nerve sparing in robot-assisted laparoscopic radical prostatectomy in a British setting - a prospective observational comparative study.

OBJECTIVES: To evaluate the neurovascular structure-adjacent frozen-section examination (NeuroSAFE) technique in a British setting in men undergoing robot-assisted laparoscopic radical prostatectomy (RALP) . PATIENTS AND METHODS: We retrospectively analysed our prospectively maintained database of patients who underwent RALP between November 2008 and February 2017. We examined preoperative pathological and functional parameters, intraoperative nerve sparing (NS), postoperative histology, as well as functional and oncological follow-up. We compared those who had a NeuroSAFE approach and those who had NS without NeuroSAFE. We also compared all the RALPs before and after the introduction of NeuroSAFE. Statistical analysis was done using the two-tailed t-test and chi-squared analysis. RESULTS: This single surgeon series included 417 RALPs, including 120 NeuroSAFEs. The NeuroSAFE cohort had a greater proportion of D'Amico high-risk disease (30.8% vs 9.6%, P < 0.001), higher Gleason scores and higher pT stage compared to the non-NeuroSAFE NS cohort. After the introduction of NeuroSAFE, more preoperatively potent men underwent bilateral NS with pT2 disease (84.6% vs 66.3%, P = 0.002) and more overall NS were performed in patients with pT3 disease (65.1% vs 36.7%, P = 0.012). Overall positive surgical margin (PSM) rates were lower in the NeuroSAFE cohort compared to those who had NS without NeuroSAFE (9.2% vs 17.8%, P = 0.04). The 12-month potency rates were also higher in the NeuroSAFE cohort for both bilateral (77.3% vs 50.9%, P = 0.009) and unilateral (70.6% vs 40%, P = 0.04) NS. Pad-free continence was also higher in the NeuroSAFE group (85.7% vs 70.9%, P = 0.019), but there was no significant difference between those who were wearing ≤1 safety pad. Although we only had short-term oncological follow-up, it did not significantly differ between the two groups. CONCLUSION: Adoption of NeuroSAFE allowed us to offer NS in higher risk patients, whilst reducing PSM rates and at the same time improving potency at 12 months.

Can Anterior Prostatic Fat Harbor Prostate Cancer Metastasis? A Prospective Cohort Study.

OBJECTIVES: Traditionally anterior prostatic fat (APF) hasn't been included in pelvic lymph node (LN) dissection templates following radical prostatectomy. In this study we evaluate the incidence of lymphoid tissue in the APF and the incidence of LN metastasis in APF in patients who have undergone robotic-assisted laparoscopic radical prostatectomy (RALP). METHODS: A prospective database of RALP has been maintained between January 2010 and September 2015. APF is routinely excised and sent separately for histopathological evaluation to identify lymphoid tissue and metastatic prostate cancer. RESULTS: A total of 629 underwent RALP. Forty-six (7.3%) of the patients had lymphoid tissue on histopathological evaluation. Two patients had meta-static disease. Both patients with positive LNs were intermediate risk on pre-operative evolution (A-PSA 16.6 ng/ml, Gleason 3 + 4; B PSA 7.3 ng/ml, Gleason 4 + 3) and upgraded on final prostate pathological evaluation to high risk disease (A-Gleason 4 + 5, pT3b, B-Gleason 4 + 3, pT4). CONCLUSION: There appears to be lymphatic drainage to the APF from the prostate. Hence APF should be included in pelvic LN dissection templates when lymphadenectomy is contemplated in patients undergoing radical prostatectomy.

Atypical Small Acinar Proliferation and High Grade Prostatic Intraepithelial Neoplasia: Should We Be Concerned? An Observational Cohort Study with a Minimum Follow-Up of 3 Years.

INTRODUCTION: Atypical small acinar proliferation (ASAP) and high grade prostatic intraepithelial neoplasia (HGPIN) are considered precancerous. We aimed to measure the rate of repeat biopsy and adenocarcinoma in patients with ASAP and HGPIN and identify any clinico-pathologic parameters at diagnosis of ASAP/HGPIN that are predictive of adenocarcinoma. MATERIALS AND METHODS: Patients with a diagnosis of ASAP/HGPIN with no previous or concomitant cancer were identified. Prostate specific antigen (PSA) and magnetic resonance imaging (MRI) changes were monitored. Re-biopsy was at clinician discretion. RESULTS: Nineteen were diagnosed with ASAP and 17 with HGPIN. Seven with ASAP (37%) and 6 with HGPIN (35%) underwent re-biopsy. Three (16%) with ASAP and 5 with HGPIN (29%) were diagnosed with adenocarcinoma. The difference in cancer detection rates between ASAP and HGPIN was not significant (p = 0.35). Five (14%) in total required definitive therapy for adenocarcinoma. Twenty-three (64%) did not undergo repeat biopsy. Parameters at diagnosis of HGPIN and ASAP, including PSA, prostate volume and PSA density, were compared between the cancer and non-cancer cohorts with none found to be predictive of adenocarcinoma. CONCLUSION: By monitoring PSA and MRI changes, we managed to spare re-biopsy in two-thirds of patients. Further evaluation is necessary to characterize a surveillance protocol in these populations.

Intraoperative Frozen Section of the Prostate Reduces the Risk of Positive Margin Whilst Ensuring Nerve Sparing in Patients with Intermediate and High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy: First Reported UK Series.

INTRODUCTION: Nerve sparing during robotic radical prostatectomy (RRP) considerably improves post-operative potency and urinary continence as long as it does not compromise oncological outcome. Excision of the neurovascular bundle (NVB) is often performed in patients with intermediate and high risk prostate cancer to reduce the risk of positive surgical margin raising the risk of urinary incontinence and impotence. We present the first UK series outcomes of such patients who underwent an intra-operative frozen section (IOFS) analysis of the prostate during RRP allowing nerve sparing. PATIENTS AND METHODS: We prospectively analysed the data of 40 patients who underwent an IOFS during RRP at our centre from November 2012 until November 2014. Our IOFS technique involved whole lateral circumferential analysis of the prostate during RRP with the corresponding neurovascular tissue. An intrafascial nerve spare was performed and the specimen was removed intra-operatively via an extension of the 12 mm Autosuture™ camera port without undocking robotic arms. It was then painted by the surgeon and sprayed with "Ink Aid" prior to frozen section analysis. The corresponding NVB was excised if the histopathologist found a positive surgical margin on frozen section. RESULTS: Median time to extract the specimen, wound closure and re-establishment of pneumoperitoneum increased the operative time by 8 min. Median blood loss for IOFS was 130 ± 97 ml vs. 90 ± 72 ml (p = NS). IOFS was not associated with major complications or with blood transfusion. PSM decreased significantly from non-IOFS RRP series of 28.7 to 7.8% (p < 0.05). Intra-operative PSM on the prostate specimen was seen in 8/40 margin analysis (20%) leading to an excision of the contra-lateral nerve bundle. On analysis of the nerve bundle on a paraffin embedded block, 6 nerve bundle matched tumor on the specimen whereas 2 NVB were retrospectively removed unnecessarily in our series. All 40 patients have undetectable PSA at a mean follow up of 21.2 months (SD 7.79). Functional data at 18 months confirms a reduction in the urinary incontinence from 37% in the IOFS group vs 57% in the non-IOFS group (p = NS). IOFS technique has resulted in a significant increase in intravesical nerve sparing in both T2/T3 patients with intermediate and high risk prostate cancer when appropriately counselled and selected (T2 from 100% in the IOFS group versus 67% and T3 from 100% in the IOFS group to 42%) (p < 0.05). CONCLUSION: Introduction of the IOFS analysis during intrafascial nerve spare RRP has reduced PSM and the rate of urinary incontinence.