Low rate of severe-end-stage kidney disease after SABR for localised primary kidney cancer.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC. METHODS AND MATERIALS: This was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012-2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan-Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models. RESULTS: Seventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70-83), tumor size of 4.5 cm (IQR 3.9-5.8) and follow-up of 42.2 months (IQR 23-60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1-2. By last follow-up, 1/35 (2.8%) of baseline CKD 1-2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4-5. The estimated probability of freedom from CKD stage 4-5 at 1 and 5 years was 89.6% (CI 83.0-97.6) and 65% (CI 51.4-81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4-5 CKD though only the former remained significant in multivariable model. CONCLUSION: In this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.

Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study.

BACKGROUND: High-risk localised prostate cancer (HRCaP) has high rates of biochemical recurrence; [177Lu]Lu-PSMA-617 is effective in men with advanced prostate cancer. OBJECTIVE: To investigate the dosimetry, safety, and efficacy of upfront [177Lu]Lu-PSMA-617 in men with HRCaP prior to robotic radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In this single-arm, phase I/II trial, we recruited men with HRCaP (any of prostate-specific antigen [PSA] >20 ng/ml, International Society of Urological Pathology (ISUP) grade group [GG] 3-5, and ≥cT2c), with high tumour uptake on [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PSMA PET/CT), and scheduled for RP. INTERVENTION: Cohort A (n = 10) received one cycle and cohort B (n = 10) received two cycles of [177Lu]Lu-PSMA-617 (5 GBq) followed by surgery 6 weeks later. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was tumour radiation absorbed dose. Adverse events (AEs; Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), surgical safety (Clavien-Dindo), imaging, and biochemical responses were evaluated (ClinicalTrials.gov: NCT04430192). RESULTS AND LIMITATIONS: Between May 29, 2020 and April 28, 2022, 20 patients were enrolled. The median PSA was 18 ng/ml (interquartile range [IQR] 11-35), Eighteen (90%) had GG ≥3, and six (30%) had N1 disease. The median (IQR) highest tumour radiation absorbed dose after cycle 1 for all lesions was 35.5 Gy (19.5-50.1), with 19.6 Gy (11.3-48.4) delivered to the prostate. Five patients received radiation to lymph nodes. Nine (45%) patients achieved >50% PSA decline. The most common AEs related to [177Lu]Lu-PSMA-617 were grade 1 fatigue in eight (40%), nausea in seven (35%), dry mouth in six (30%), and thrombocytopenia in four (20%) patients. No grade 3/4 toxicities or Clavien 3-5 complications occurred. Limitations include small a sample size. CONCLUSIONS: In men with HRCaP and high prostate-specific membrane antigen (PSMA) expression, [177Lu]Lu-PSMA-617 delivered high levels of targeted radiation doses with few toxicities and without compromising surgical safety. Further studies of [177Lu]Lu-PSMA-617 in this population are worthwhile to determine whether meaningful long-term oncological benefits can be demonstrated. PATIENT SUMMARY: In this study, we demonstrate that up to two cycles of [177Lu]Lu-PSMA-617 given prior to radical prostatectomy in patients with high-risk localised prostate cancer are safe and deliver targeted doses of radiation to tumour-affected tissues. It is tolerated well with minimal treatment-related adverse events, and surgery is safe with a low rate of complications. Activity measured through PSA reduction, repeat PSMA PET/CT, and histological response is promising.

Metabolic and magnetic resonance imaging: complementary modalities for the preoperative assessment of lateral pelvic lymph nodes in rectal cancer.

BACKGROUND: The management of lateral pelvic lymph nodes for rectal cancer is a topical and controversial issue. The aim of this study was to assess the relationship between lateral pelvic lymph node features on magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) with oncological outcomes in patients with rectal cancer. METHODS: A retrospective analysis of 284 patients with primary locally advanced rectal cancer treated with neoadjuvant therapy and surgical resection with curative intent between January 2003 and Dec 2018 was undertaken. From this study population, a select cohort of 77 patients with abnormal lateral pelvic lymph nodes on preoperative imaging had imaging re-analysed by radiologists blinded to clinical outcomes. Pre and post neoadjuvant therapy MRI and PET-CT lateral pelvic lymph node features were correlated with oncological outcomes. RESULTS: A lateral pelvic lymph node short axis size ≥5 mm on post neoadjuvant therapy MRI was a significant predictor of worse 3-year local recurrence free survival (HR 8.35, P = 0.001). Lateral pelvic lymph node avidity on post neoadjuvant therapy PET-CT was a significant predictor of worse 3-year distant recurrence free survival (HR 5.62, P = 0.001). No correlation of oncological outcomes with overall survival was identified. CONCLUSION: Lateral pelvic lymph node imaging features on post-neoadjuvant therapy MRI and PET-CT predicted those at risk of rectal cancer recurrence. Further studies are required to confirm these findings that suggest restaging MRI and PET-CT are complementary modalities for the preoperative assessment of lateral pelvic lymph nodes in rectal cancer.

The identification and internal validation of a preoperative serum biomarker panel to determine extracapsular extension in patients with prostate cancer.

BACKGROUND: Accurate preoperative staging of prostate cancer (PCa) is important but current diagnostic methods cannot accurately determine extracapsular extension (ECE), resulting in the possible triage of patients towards a less appropriate arm of therapy. This has consequences to patient care and better methods of preoperatively determining ECE are required. METHODS: We followed a biomarker development pathway and compared the preoperative serum expressions of VEGF-D, PEDF, IGF-I, IGFBP3, and CD14 in patients from the Irish Prostate Cancer Research Consortium (PCRC) with radical prostatectomy determined ECE against patients with nonECE. RESULTS: The expression measurements of five proteins were fitted into a logistic regression model and backwards variable elimination methods were applied which resulted in a model with IGFBP3 and CD14 as the best combination biomarker panel. This panel was tested in an independent cohort of patients using an optimized multiplex electrochemiluminescence assay. Receiver operating characteristic curves were generated and the areas under the curve (AUC) were calculated as an estimation of prediction accuracy. The biomarker panel was validated with an AUC of 76.6%, and a sensitivity and specificity of 80% and 75% was obtained. CONCLUSIONS: This is the first internally validated, preoperative serum biomarker panel that identifies ECE in patients with Gleason score 7 PCa with AUC 76.6%. The panel surpasses the routinely used diagnostic standards in accuracy and may help to improve preoperative cancer staging, better inform treatment options, and improve the referral patterns of patients with urgently treatable cancers towards more appropriate arms of therapy.

Epstein criteria for insignificant prostate cancer.

UNLABELLED: Study Type - Prognosis (systematic review). LEVEL OF EVIDENCE: 2b. What's known on the subject? and What does the study add? Overtreatment of prostate cancer is a major problem in contemporary urological practice. The Epstein Criteria reduces overtreatment by identifying insignificant prostate cancers that may be amenable to surveillance therapy. This systematic review of the Epstein Criteria validation studies provides a collective insight into the application and accuracy of the Epstein Criteria to predict for insignificant prostate cancer across different institutions and geographies. OBJECTIVE: • To review the accuracy of the Epstein Criteria for insignificant prostate cancer and to explore the effect of the modified Gleason classification system on this system. METHODS: • We searched PubMed, EMBASE and the Cochrane Database using search terms 'Epstein Criteria', 'Prostate Cancer', 'Validation' and 'Insignificant Cancer' between 1994 to 2010 for validation articles. • These were divided into pre-2005 and post-2005 and concordances for organ-confined status, Gleason score ≤ 6 and insignificant cancer were analysed. RESULTS: • A pre-2005 study showed concordance for insignificant prostate cancer, Gleason score ≤ 6 and organ-confined status at 84%, 90.3% and 91.6%, respectively. • Five post-2005 validation studies were concordant for insignificant cancer, Gleason score ≤ 6 and organ-confined status at 37-76%, 54.3-75.9% and 80.0-96.9%, respectively. CONCLUSIONS: • The Epstein Criteria has a suboptimal accuracy for predicting for insignificant prostate cancer. • The modification to Gleason scoring may be responsible for a reduced accuracy over time. • However, significant heterogeneity in the validation studies means better quality validation studies are required.

Do antispasmodics or rectal enemas improve image quality on multiparametric prostate MRI? An 'Evidence-Based Practice' review of the literature.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate is increasingly used for the preoperative detection and staging of prostate cancer. Image quality of prostate mpMRI can be significantly degraded by motion related artefact due to bowel peristalsis and susceptibility related artefact, which reduces cancer detection sensitivity. The use of several different methods including anstispasmodic medications and rectal enemas were proposed as potential methods to reduce mpMRI artefacts, but current recommendations in the scientific literature are conflicting and inconsistent. This article seeks to identify the best available evidence to determine which patient preparation method is most effective in improving prostate mpMRI, and provides recommendations for further areas of research. We used the five-step 'Evidence-Based Practice' systematic approach of 'Ask, Search, Appraise, Apply and Evaluate' described by the McMaster University and National Health Service for critical appraisal of topics. We developed a focused clinical question using a PICO format, and performed a primary and secondary literature search through Ovid Medline, Ovid Embase and Cochrane CENTRAL (Wiley). All identified articles were appraised for strength and validity. Seven articles were retrieved which demonstrated conflicting sensitivities and specificities for intravenous hyoscine butylbromide and rectal enema in improving image susceptibility artefact, motion artefact, and anatomic distortion on the T2 or diffusion weighted imaging sequences. Intravenous hysoscine butylbromide is the optimum patient preparation method for improving T2W and DWI image quality in prostate mpMRI. The use of a preparatory rectal enema is not currently recommended, but better quality studies are required.

Contrast-enhanced ultrasound of the kidney: a single-institution experience.

BACKGROUND: Focal renal masses are typically evaluated by means of triphasic contrast-enhanced CT or MRI scan but use of iodinated contrast or gadolinium is unsuitable for some patients. Contrast-enhanced ultrasound (CEUS) is an imaging alternative in this scenario but has limited availability in Ireland. AIM: The aim of the study was to retrospectively evaluate experience with selective use of CEUS for non-invasive characterization of focal renal masses in a tertiary referral institution in Ireland, with a particular focus on cystic renal lesions and the influence of CEUS on final Bosniak classification and treatment outcomes. METHODS: All cases of renal CEUS between 2009 and 2017 were identified. Imaging history, patient records, histopathology reports, urology conference notes, clinical follow-up details, details of lesion progression or stability on surveillance, biopsy and/or resection details and pre- and post-CEUS Bosniak scores were recorded. RESULTS: Thirty-one patients underwent renal CEUS (7 solid renal lesions, 21 cystic renal lesions and 3 'indeterminate' renal lesions). After CEUS, the CEUS-modified Bosniak score was upgraded in nine patients and downgraded in two patients. All three lesions upgraded from Bosniak III to IV were renal cell carcinomas. One of two lesions downgraded from Bosniak IV to III was resected (cystic nephroma) and the other showed no progression after 19 months of surveillance. CONCLUSION: CEUS is a valuable alternative to CT in assessing complex cystic or solid renal lesions where iodinated CT contrast or gadolinium is inappropriate. CEUS can also refine the Bosniak category of atypical cystic renal lesions and help facilitate treatment decisions.

Evaluation of suspected renal colic with noncontrast CT in the emergency department: a single institution study.

BACKGROUND AND PURPOSE: Noncontrast CT (NCCT) has become the standard Imaging study in the emergency department (ED) diagnosis of nephro- and ureterolithiasis. We undertook to audit the results from the first 500 NCCTs performed for patients presenting to the ED with suspected renal colic. PATIENTS AND METHODS: In a retrospective study at one institution from October 2003 to February 2006, 500 patients with suspected stone disease were investigated. In the study, NCCT findings, patient clinical records, and urinary microscopy results were evaluated for 166 women and 334 men. RESULTS: Renal or ureteral calculi were identified in 279 (56%) of NCCTs performed. Of the 500, 112 (19%) NCCTs performed identified unexpected intra-abdominal pathology. When the findings deemed to be of low clinical significance were excluded, the number of scans with additional pathology amounted to 67 (13%). These included vascular emergencies, new cancer diagnoses, and gastrointestinal conditions. CONCLUSIONS: The variety of diagnoses found unexpectedly on the NCCT that alter a patient's treatment demonstrates the pivotal role of NCCT in the triage of these patients rapidly toward optimal therapy. The rapid acquisition time of NCCT has enabled definitive ED patient diagnosis and less bed occupancy for clinically insignificant calculi.