Rajan Gupta

PURPOSE: PI-RADS 4 lesions are considered to have a "high" likelihood of clinically-significant prostate cancer (csPCa). However, patients undergoing targeted biopsy have a range of histologic findings. Understanding discordant cases is critical to improve diagnostic accuracy and inform subsequent management. We studied early findings from implementation of a multidisciplinary Quality Improvement (QI) protocol for reconciling discordance and evaluate the potential heterogeneity of PI-RADS 4. METHODS: Patients with mpMRI PI-RADS 4 lesions undergoing fusion-targeted biopsy from January 2017 to May 2021 were retrospectively reviewed. The discordant targeted biopsy pathology (benign/GG1) was evaluated utilizing a QI protocol and all lesions were subcategorized based on ADC values. Positive Predictive Value (PPV) for PI-RADS 4 lesions overall and the Cancer Detection Rate (CDR) for subcategorized lesions were calculated. RESULTS: 248 patients with 286 lesions were reviewed. Prior to re-review, PI-RADS 4 PPV for ≥ GG1 and ≥ GG2 lesions were 0.55 and 0.34, increasing to 0.67 and 0.43 following reconciliation. Lesion subcategorization based on ADC value as higher suspicion (4+) and lower suspicion (4-) resulted in 158 and 117 lesions, with reverse-fusion analysis revealing that 61% and 17% of lesions contained csPCa, respectively. Subgroup analysis among PI-RADS 4+ lesions led to an increase in the CDR to 75% and 61% for ≥ GG1 and ≥ GG2. CONCLUSION: Use of multidisciplinary QI protocol to review discordance cases of PI-RADS 4 improves diagnostic accuracy and guides subsequent management. Our findings highlight the known heterogeneity of this category with reference to csPCa CDR, suggesting the potential value of PI-RADS 4 subcategorization.

Renal cell carcinoma is a complex group of highly heterogenous renal tumors demonstrating variable biological behavior. Pretreatment imaging of renal cell carcinoma involves accurate assessment of the primary tumor, presence of nodal, and distant metastases. CT and MRI are the key imaging modalities used in the staging of renal cell carcinoma. Important imaging features that impact treatment include tumor extension into renal sinus and perinephric fat, involvement of pelvicalyceal system, infiltration into adrenal gland, involvement of renal vein and inferior vena cava, as well as the presence of metastatic adenopathy and distant metastases. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Background This guideline was prepared by the Fever Assessment Guideline Development Group, a group organized by the Program in Evidence-Based Care at the request of the Cancer Care Ontario Systemic Treatment Program. The mandate was to develop a standardized approach (in terms of definitions, information, and education) for the assessment of fever in cancer patients receiving chemotherapy. Methods The guideline development methods included a search for existing guidelines, literature searches in medline and embase for systematic reviews and primary studies, internal review by content and methodology experts, and external review by targeted experts and intended users. Results The search identified eight guidelines that had partial relevance to the topic of the present guideline and thirty-eight primary studies. The studies were mostly noncomparative prospective or retrospective studies. Few studies directly addressed the topic of fever except as one among many symptoms or adverse effects associated with chemotherapy. The recommendations concerning fever definition are supported mainly by other existing guidelines. No evidence was found that directly pertained to the assessment of fever before a diagnosis of febrile neutropenia was made. However, some studies evaluated approaches to symptom management that included fever among the symptoms. Few studies directly addressed information needs and resources for managing fever in cancer patients. Conclusions Fever in patients with cancer who are receiving systemic therapy is a common and potentially serious symptom that requires prompt assessment, but currently, evidence to inform best practices concerning when, where, and by whom that assessment is done is very limited.

PURPOSE: To define the optimal model of care for patients receiving outpatient chemotherapy who experience a fever. Fever is a common symptom in patients receiving chemotherapy, but the approach to evaluation of fever is not standardized. METHODS: We conducted a search for existing guidelines and a systematic review of the primary literature from database inception to November 2015. Full-text reports and conference abstracts were considered for inclusion. The search focused on the following topics: the relationship between temperature and poor outcome; predictors for the development of febrile neutropenia (FN); the timing, location, and personnel involved in fever assessment; and the provision of information to patients receiving chemotherapy. RESULTS: Eight guidelines and 38 studies were included. None of the guidelines were directly relevant to the target population because they dealt primarily with the management of FN after diagnosis. The primary studies tended to include fever as one of many symptoms assessed in the setting of chemotherapy. Temperature level was a weak predictor of poor outcomes. We did not find validated prediction models for identifying patients at risk of FN among patients receiving chemotherapy. Several studies presented approaches to symptom management that included fever among the symptoms, but results were not mature enough to merit widespread adoption. CONCLUSION: Despite the frequency and risks of fever in the setting of chemotherapy, there is limited evidence to define who needs urgent assessment, where the assessment should be performed, and how quickly. Future research in this area is greatly needed to inform new models of care.

INTRODUCTION: We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa). METHODS: The primary outcome was the detection of a ≥5 point deterioration in any of the four main expanded prostate index composite (EPIC) functional domains. Pretreatment multiparametric magnetic resonance imaging (mpMRI) and transperineal targeted and systematic saturation biopsy were used to select patients with prostate-specific antigen (PSA)≤20 ng/mL, Gleason grade group (GG) ≤4, mpMRI lesion volume ≤ 3 mL (for a single lesion) or ≤1.5 mL (where two lesions were present). Focal cryotherapy was performed with a minimum 5 mm margin around each target lesion. EPIC scores were obtained at baseline and posttreatment at 1, 3, 6, and 12 months. Mandatory repeat mpMRI and prostate biopsy were performed at 12 months to determine the infield and outfield recurrence. RESULTS: Twenty-eight patients were recruited. The mean age was 68 years, with PSA of 7.3 ng/mL and PSA density of 0.19 ng/mL2 . No Clavien-Dindo ≥3 complications occurred. Transient worsening of EPIC urinary (mean diff 16.0, p < 0.001, 95% confidence interval [CI]: 8.8-23.6) and sexual function scores (mean diff 11.0, p:0.005, 95% CI: 4.0-17.7) were observed at 1-month posttreatment, with recovery by Month 3. A subgroup who had ablation extending to the neurovascular bundle had a trend to delayed recovery of sexual function to Month 6. At 12-month repeat mpMRI and biopsy, 22 patients (78.6%) had no detectable csPCa. Of the six patients (21.4%) who had csPCa recurrences, four were GG2, one GG3, and one GG4. Four patients underwent repeat FT, one underwent radical prostatectomy, while the remaining one patient with low-volume GG2 cancer opted for active surveillance. CONCLUSION: FT using cryotherapy was associated with a transient deterioration of urinary and sexual function with resolution at 3 months posttreatment and with reasonable early efficacy in well-selected csPCa patients.