A Tribute to Dr. Christopher G. Wood, MD

Tributes to individuals who have passed away share one common purpose: to help us heal. We find comfort by sharing the legacies of the loved ones we’ve lost. Today we pay tribute to Dr. Christopher G. Wood, Professor of Urology.

How Can We Predict pT3a Kidney Cancer and What Does It Mean?

The ability to predict pathologically advanced renal cell carcinoma (RCC) within the primary tumor upfront can be helpful to guide prognostic counseling and hold implications for both surgical approach and multimodal therapeutic strategies. Herein, the investigators undertook a comprehensive assessment of radiographic features predictive of pT3a stage by querying 11 radiological findings across a robust retrospective cohort of patients with RCC. They found that an irregular tumor-sinus border (ITSB) correlated most strongly with pT3a stage and recurrence-free survival (RFS).

Radiological Correlates of pT3a Kidney Cancer: Importance of Irregular Tumor Sinus Border

Purpose: Preoperative assessment of T3a renal-cell-carcinoma (RCC) in absence of main renal vein involvement or lymph node enlargement is challenging but has potential implications for counseling and prognosis. Materials and Methods: A retrospective review of 1129 cT1-T3aN0M0 RCC patients managed with partial/radical nephrectomy (PN/RN) in our institution (2012-2014) was performed. Exclusion criteria included radiological evidence of main renal vein involvement or substantial lymphadenopathy. Eleven radiological findings suggestive of aggressive tumor biology or invasive phenotype based on prior literature were assessed for correlation with pT3a status. These included perinephric-findings (stranding, enhancing-nodule, collateral-vessels, or irregular-perinephric-tumor-contour), findings within the sinus (stranding, collecting-system invasion, branch-vein enlargement, or irregular-tumor-sinus-border [ITSB]), and tumor-necrosis, infiltrative-features, and tumor-size. Radiological assessment was blinded to final pathology. Sensitivity/specificity and logistic-regression analyses assessed the performance of each imaging-finding for detecting pT3a tumors. Results: Median tumor-size was 4.0cm and R.E.N.A.L. was 8. Median follow-up was 53 months (IQR:28-64). pT3a tumors were found in 281 patients (25%) and strongly correlated with local and systemic recurrence (p<0.02). ITSB was found in 350 patients (31%) and was the strongest predictor of pT3a status. Sensitivity/specificity/PPV/NPV/OR/C-Index for ITSB were 75%/84%/61%/91%/15.8(11.4-21.9)/0.80, for correlation with pT3a, respectively. The best predictive model included ITSB(yes/no) and tumor-size as a continuous variable (C-index=0.84). Addition of other imaging-findings did not improve the model (C-index=0.84). ITSB was the strongest contributor in all multivariable-models and also strongly correlated with recurrence-free-survival. Inter/intra-observer correlations for assessment of ITSB were 0.89/0.98, respectively. Conclusions: Our data suggest that ITSB and tumor-size associate with pT3a RCC, which could impact patient counseling.

Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial

Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor-risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.

Expert perspectives on currently evolving therapeutic landscape of metastatic renal cell carcinoma: Nicholas J. Vogelzang, MD, FASCO, FACP.

The major phenomenon that we are all dealing in the kidney cancer space is the power of the immuno-oncology agents to effect complete responses. For the first- line therapy, physicians have f our FDA approved regimens to choose from: nivolumab/ipilimumab, pembrolizumab/axitinib, nivolumab/cabometyx, pembro/lenvantinib, and of course clinical trials. Nivolumab/ipilimumab combination has big advantages and performs dramatically well in eliminating the tumors in certain RCC patients. In some patients, complete response is attained fairly quickly within three months. Such complete responses are well documented both clinically and sometimes surgically by nephrectomy. Such highly impressive outcomes are driving a lot of physicians who are on the fence between nivolumab/ipilimumab versus pembrolizumab/axitinib to go with nivolumab and ipilimumab.

The Current and Evolving Therapeutic Paradigm in the Management of Metastatic Renal Cell Carcinoma

There has been tremendous progress in the treatment landscape of advanced or metastatic RCC with novel and efficacious targeted therapies, immunotherapies and combinatorial regimens, leading to an expansion of therapeutic armamentarium over the last two decades. New advances have offered considerable improvement in prognosis, treatment-related toxicities, quality of life, and survival for patients with mRCC. Despite such advantages, there is unmet need for developing novel biomarkers predictive of treatment response, optimize treatment selection, and also improving strategies to overcome therapeutic resistance in heterogenous RCC tumors. Herein, we outline currently available first- and subsequent-lines treatment strategies, unprecedented changes, and also discuss challenges in treatment landscape of RCC.

mTOR and VEGF Tissue Biomarkers and Sunitinib/Everolimus Outcomes in Non-Clear Cell Renal Cancer

Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.

Editor's Memo

The COVID-19 pandemic has exposed fundamental disparities in the provision of health care across our nation and exacerbated the differences in health outcomes associated with race, socioeconomic and other demographic factors. A silver lining however is that pandemic precarity has inspired tremendous scientific collaboration among clinicians, researchers, and key opinion leaders. In this line, this year’s Annual Meeting of the American Society of Clinical Oncology (ASCO21) which was kicked off virtually on June 4 through June 8, not only celebrated latest breakthroughs in cancer research, treatment and patient care, but also focused on health equity in cancer care. ASCO21’s fitting theme - Health equity “doing right by the patients for whom we care” reflected addressing complex forces and systems that have created disparities in cancer care, treatment, and research and identifying ways to ensure that all patients have access to and benefit from the latest cancer advances and high-quality cancer care.

Practice Changing Results in RCC come from ASCO 2021

For the second year in a row, the annual meeting of the American Society of Clinical Oncology (ASCO) was held virtually due to the ongoing COVID-19 pandemic. Nonetheless, the meeting was hailed as a great success and brought much practice changing data in the field of genitourinary medical oncology, including kidney cancer.