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Background and objective: Clinical practice guidelines for prostate cancer (PCa) are a valuable resource for everyday clinical practice. The clinical practice guidelines and recommendations produced by various societies should demonstrate a considerable level of consistency in terms of quality, regardless of the society that developed these given the common evidence base. However, to date, no study has assessed the quality of PCa clinical practice guidelines. As part of the Optimal Treatment for Patients with Solid Tumours in Europe Through Artificial intelligence (OPTIMA) project, we evaluated the quality of the most frequently used national and international clinical practice guidelines for PCa using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool. Methods: The quality of the identified clinical practice guidelines was assessed independently by two assessors using the AGREE II tool. The AGREE II tool comprises 23 different items organised into six domains, rated on a 7-point scale (1: strongly disagree to 7: strongly agree). The total score of the appraisal was the mean value of the two assessments. The agreement between assessors’ scores was calculated using the interclass correlation coefficient (ICC). Four key recommendations were compared among the included clinical practice guidelines to assess consistency. Key findings and limitations: Sixteen clinical practice guidelines were assessed using their latest available version (cut-off April 2024). The European Association of Urology, S3LL PCa, Belgian Health Care Knowledge Centre, National Comprehensive Cancer Network, and Prostatacancer—Nationellt vårdprogram guidelines received the highest overall scores with a mean domain score of 82.4% (range: 75.5–88.3%). The de l’Association Française d’Urologie (AFU), American Urological Association, and National Institute for Health and Care Excellence received a mean domain score of 77.6% (range: 73.7–84.0%). Below average were the European Society for Medical Oncology, localised (L) and systemic (S) CPPC American Society of Clinical Oncology, and Nederlandse Vereniging voor Urologie (NVU) with a mean domain score of 58.4% (range: 43.5–76.3%). The reasons for scoring below average included the following: inadequate information about the methodology applied, limited scope of the guideline, and limited patient engagement. The highest inter-rater variability was observed in NVU (ICC: 0.58) and the lowest in AFU-L (ICC: 0.84). When examining the scores of each domain, “clarity of presentation” (domain 4) achieved the highest score with a mean of 86.9% ± 12.6%. The domain with the lowest score was applicability (domain 5), with a mean of 48.3% ± 24.8%. The ICC was calculated to be 0.72 (±0.08). Conclusions and clinical implications: This is the first study in which a comprehensive quality assessment of the majority of international and national clinical practice guidelines was undertaken, and the key recommendations were compared to assess consistency. Our study shows that the majority of international and national clinical practice guidelines demonstrate high-quality standards when assessed using the AGREE II evaluation tool. The clinical practice guidelines that did not meet the expected standards could be improved by adopting several key recommendations outlined by our study. Patient summary: The OPTIMA project used the Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool to evaluate the quality of 16 commonly used national and international clinical practice guidelines for prostate cancer. While some of these international and national clinical practice guidelines received the highest score, few guidelines scored below average due to methodological deficiencies and limited patient engagement. These findings highlight the need for a standardised process to ensure high-quality, consistent guidelines across practices.

Context: Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications. Objective: The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain. Evidence acquisition: A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function. Evidence synthesis: After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain. Conclusions: Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain. Patient summary: Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.

Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making. One solution is a core outcome set (COS): an agreed minimum set of outcomes. Objective: To describe outcome reporting, definitions, and measurement heterogeneity as the first stage in co-creating a COS for localised renal cancer. Evidence acquisition: We systematically reviewed outcome reporting heterogeneity in effectiveness trials and observational studies in localised RCC. In total, 2822 studies (randomised controlled trials, cohort studies, case-control studies, systematic reviews) up to June 2020 meeting our inclusion criteria were identified. Abstracts and full texts were screened independently by two reviewers; in cases of disagreement, a third reviewer arbitrated. Data extractions were double-checked. Evidence synthesis: We included 149 studies and found that there was inconsistency in which outcomes were reported across studies and variability in the definitions used for outcomes that were conceptually the same. We structured our analysis using the outcome classification taxonomy proposed by Dodd et al. Outcomes linked to adverse events (eg, bleeding, outcomes linked to surgery) and renal injury outcomes (reduced renal function) were reported most commonly. Outcomes related to deaths from any cause and from cancer were reported in 44% and 25% of studies, respectively, although the time point for measurement and the analysis methods were inconsistent. Outcomes linked to life impact (eg, global quality of life) were reported least often. Clinician-reported outcomes are more frequently reported than patient-reported outcomes in the renal cancer literature. Conclusions: This systematic review underscores the heterogeneity of outcome reporting, definitions, and measurement in research on localised renal cancer. It catalogues the variety of outcomes and serves as a first step towards the development of a COS for localised renal cancer. Patient summary: We reviewed studies on localised kidney cancer and found that multiple terms and definitions have been used to describe outcomes. These are not defined consistently, and often not defined at all. Our review is the first phase in developing a core outcome set to allow better comparisons of studies to improve medical care.

Background: No liquid biomarkers are approved in renal cell carcinoma (RCC), making early detection of recurrence in surgically treated nonmetastatic (M0) patients dependent on radiological imaging. Urine- and plasma free glycosaminoglycan profiles—or free GAGomes—are promising biomarkers reflective of RCC metabolism. Objective: To explore whether free GAGomes could detect M0 RCC recurrence noninvasively. Design, setting, and participants: Between June 2016 and February 2021, we enrolled a prospective consecutive series of patients elected for (1) partial or radical nephrectomy for clinical M0 RCC (cohort 1) or (2) first-line therapy following RCC metachronous metastatic recurrence (cohort 2) at Sahlgrenska University Hospital, Gothenburg, Sweden. The study population included M0 RCC patients with recurrent disease (RD) versus no evidence of disease (NED) in at least one follow-up visit. Plasma and urine free GAGomes—consisting of 40 chondroitin sulfate (CS), heparan sulfate, and hyaluronic acid (HA) features—were measured in a blinded central laboratory preoperatively and at each postoperative follow-up visit until recurrence or end of follow-up in cohort 1, or before treatment start in cohort 2. Outcome measurements and statistical analysis: We used Bayesian logistic regression to correlate GAGome features with RD versus NED and with various histopathological variables. We developed three recurrence scores (plasma, urine, and combined) proportional to the predicted probability of RD. We internally validated the area under the curve (AUC) using bootstrap resampling. We performed a decision curve analysis to select a cutoff and report the corresponding net benefit, sensitivity, and specificity of each score. We used univariable analyses to correlate each preoperative score with recurrence-free survival (RFS). Results and limitations: Of 127 enrolled patients in total, 62 M0 RCC patients were in the study population (median age: 63 year, 35% female, and 82% clear cell). The median follow-up time was 3 months, totaling 72 postoperative visits —17 RD and 55 NED cases. RD was compatible with alterations in 14 (52%) of the detectable GAGome features, mostly free CS. Eleven (79%) of these correlated with at least one histopathological variable. We developed a plasma, a urine, and a combined free CS RCC recurrence score to diagnose RD versus NED with AUCs 0.91, 0.93, and 0.94, respectively. At a cutoff equivalent to ≥30% predicted probability of RD, the sensitivity and specificity were, respectively, 69% and 84% in plasma, 81% and 80% in urine, and 80% and 82% when combined, and the net benefit was equivalent to finding an extra ten, 13, and 12 cases of RD per hundred patients without any unnecessary imaging for plasma, urine, and combined, respectively. The combined score was prognostic of RFS in univariable analysis (hazard ratio = 1.90, p = 0.02). Limitations include a lack of external validation. Conclusions: Free CS scores detected postsurgical recurrence noninvasively in M0 RCC with substantial net benefit. External validity is required before wider clinical implementation. Patient summary: In this study, we examined a new noninvasive blood and urine test to detect whether renal cell carcinoma recurred after surgery.