Eligibility and Radiologic Assessment for Adjuvant Clinical Trials in Kidney Cancer

Abstract

To harmonize the eligibility criteria and radiologic disease assessment definitions in clinical trials of adjuvant therapy for renal cell carcinoma (RCC).METHOD On November 28, 2017, US-based experts in RCC clinical trials, including medical oncologists, urologic oncologists, regulators, biostatisticians, radiologists, and patient advocates, convened at a public workshop to discuss eligibility for trial entry and radiologic criteria for assessing disease recurrence in adjuvant trials in RCC. Multiple virtual meetings were conducted to address the issues identified at the workshop. RESULTSThe key workshop conclusions for adjuvant RCC therapy clinical trials were as follows. First, patients with non-clear cell RCC could be routinely included, preferably in an independent cohort. Second, patients with T3-4, N+M0, and microscopic R1 RCC tumors may gain the greatest advantages from adjuvant therapy. Third, trials of agents not excreted by the kidney should not exclude patients with severe renal insufficiency. Fourth, therapy can begin 4 to 16 weeks after the surgical procedure. Fifth, patients undergoing radical or partial nephrectomy should be equally eligible. Sixth, patients with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials. Seventh, all suspicious regional lymph nodes should be fully resected. Eighth, computed tomography should be performed within 4 weeks before trial enrollment; for patients with renal insufficiency who cannot undergo computed tomography with contrast, noncontrast chest computed tomography and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be performed. Ninth, when feasible, biopsy should be undertaken to identify any malignant disease. Tenth, when biopsy is not feasible, a uniform approach should be used to evaluate indeterminate radiologic findings to identify what constitutes no evidence of disease at trial entry and what constitutes radiologic evidence of disease. Eleventh, a uniform approach for establishing the date of recurrence should be included in any trial design. Twelfth, patient perspectives on the use of placebo, conditions for unblinding, and research biopsies should be considered carefully during the conduct of an adjuvant trial. CONCLUSIONS AND RELEVANCEThe discussions suggested that a uniform approach to eligibility criteria and radiologic disease assessment will lead to more consistently interpretable trial results in the adjuvant RCC therapy setting.

Prognostic significance of pathologic nodal positivity in non-metastatic patients with renal cell carcinoma who underwent radical or partial nephrectomy

“…A recent study from Raddia et al supported our findings, and they suggested that the thorough clinical staging with preoperative imaging studies was an important factor for identifying the high-risk LN+ group and providing the beneficiary role of LND in the survival outcomes of nmRCC patients who underwent curative nephrectomy 20,21 . In these backgrounds, a recent adjuvant clinical trial suggesting several eligibility and radiologic assessments for kidney cancer that either CT or MRI within 4 weeks should be performed, and every patient with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials to all suspicious regional lymph nodes 22 . Thus, previous papers supported the complete removal of suspicious LN, and the efficacy of LN dissection is important for survival prognoses [22][23][24] .…”

“…In these backgrounds, a recent adjuvant clinical trial suggesting several eligibility and radiologic assessments for kidney cancer that either CT or MRI within 4 weeks should be performed, and every patient with microscopically positive soft tissue or vascular margins without gross residual or radiologic disease may be included in trials to all suspicious regional lymph nodes 22 . Thus, previous papers supported the complete removal of suspicious LN, and the efficacy of LN dissection is important for survival prognoses [22][23][24] . Babaian et al 23 showed the effectiveness of LN dissection in 1270 nmRCC patients and reported that OS, CSS, and RFS among pNx, pN0, and pN1 cases were statistically significant (p < 0.001).…”

Accuracy of CT texture analysis for differentiating low-grade and high-grade renal cell carcinoma: systematic review and meta-analysis

“…Low-grade RCC patients may undergo partial nephrectomy, whereas high-grade RCC patients may require more invasive and extensive surgery. 34 As an important prognostic factor, it is important to preoperatively differentiate the grade of RCC in clinical practice and provide more valuable guidance for clinicians.…”

Eligibility Criteria and Endpoints in Metastatic Renal Cell Carcinoma Trials

“…Differences in renal function may affect trial results; for example, patients with chronic renal dysfunction may have shorter survival. 35 Thus, trials requiring better renal function may generate better results. In total, 3/4 trials requiring a higher creatinine clearance were newer immunotherapy trials, possibly because of concern that immunotherapies may cause immune-mediated renal injury.…”

“…Some also suggest loosening or omiting renal function criteria altogether from RCC trials if study agents are not renally metabolized, thus expanding access to clinical trials for RCC patients. 35 The 29 mRCC trials also differed in whether or not they considered patients with CNS metastases as trial eligible. Over one third of the trials disallowed CNS metastases (Fig.…”