Kidney Cancer - Volume 7, issue 1

Authors: Wang, Luke L. | Saidian, Ava | Pan, Elizabeth | Panian, Justine | Derweesh, Ithaar H. | McKay, Rana R.

Article Type: Review Article

Abstract: The standard of care for localized renal cell carcinoma (RCC) is radical or partial nephrectomy. Despite complete resection, a subset of patients will develop locoregional recurrence or metastatic disease. Adjuvant immunotherapy has been studied since the 1980 s as the primary method to mitigate tumor recurrence after definitive surgery. We herein discuss published and ongoing clinical trials investigating adjuvant therapy in localized or locoregional RCC.

DOI: 10.3233/KCA-220014

Citation: Kidney Cancer, vol. 7, no. 1, pp. 1-11, 2023

Authors: Hapke, Robert | Venton, Lindsay | Rose, Kristie Lindsay | Sheng, Quanhu | Reddy, Anupama | Prather, Rebecca | Jones, Angela | Rathmell, W. Kimryn | Haak, Scott M.

Article Type: Correction

DOI: 10.3233/KCA-229010

Citation: Kidney Cancer, vol. 7, no. 1, pp. 13-14, 2023

Authors: Sharma, Akanksha | Elias, Roy | Christie, Alana | Williams, Noelle S. | Pedrosa, Ivan | Bjarnason, Georg A. | Brugarolas, James

Article Type: Correction

DOI: 10.3233/KCA-229030

Citation: Kidney Cancer, vol. 7, no. 1, pp. 15-15, 2023

Authors: Parikh, Mamta

Article Type: Other

DOI: 10.3233/KCA-239001

Citation: Kidney Cancer, vol. 7, no. 1, pp. 17-18, 2023

Authors: Major, C. Kendall | Rodriguez, Carlos I. | Haas, Naomi B.

Article Type: Systematic Review

Abstract: BACKGROUND: The historical standard of care for locally advanced renal cell carcinoma (RCC) is nephrectomy + active surveillance. Despite a high recurrence rate ( 40%), adjuvant therapy was previously not included in the standard of care. This review of adjuvant pharmacotherapy reflects conflicting results from multiple trials. OBJECTIVE: The objective of this review is to summarize the efficacy of therapy vs surveillance in resected early-stage intermediate to high-risk renal cell carcinoma. METHODS: We performed a systematic literature search using PubMed, EMBASE, and SCOPUS. Keywords such as “renal cell carcinoma”, “adjuvant therapy” and “nephrectomy” were used. In the …literature search, 2,711 studies were identified and screened. RESULTS: We included a total of 21 publications. The most common histology seen in trials was clear cell carcinoma. A variety of interventions were reviewed including immunotherapy, medroxyprogesterone acetate, interferon alfa, and tyrosine kinase inhibitors. Most trials did not demonstrate a benefit in relapse-free survival (RPS) or overall survival (OS). Pembrolizumab demonstrated a significant difference in disease recurrence in the KEYNOTE-564 trial although median data was not reached. Blinded independent reviewers identified a benefit in disease-free survival (DFS) with Sunitinib in the S-TRAC trial. CONCLUSION: There was not a clear benefit in using adjuvant therapy broadly for resected locoregional RCC; however, further investigation should be done in the highest-risk group to elucidate potential benefit. Show more

Keywords: Renal cell carcinoma, adjuvant therapy, immunotherapy, nephrectomy, systematic review

DOI: 10.3233/KCA-220018

Citation: Kidney Cancer, vol. 7, no. 1, pp. 19-35, 2023

Authors: Uhlig, Annemarie | Uhlig, Johannes | Woike, Michael | Fischer, Thomas | Trojan, Lutz | Bergmann, Lothar | Bögemann, Martin | Goebell, Peter J. | Rink, Michael | Schlack, Katrin | Leitsmann, Marianne | Strauß, Arne

Article Type: Research Article

Abstract: Objective: To evaluate the effectiveness and safety profile of the tyrosine kinase inhibitor Axitinib for patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Methods: Adult patients from the German non-interventional post-approval multicenter STAR-TOR registry with a/mRCC (NCT00700258) were included if treated with Axitinib in second line or beyond. Overall survival (OS), progression-free survival (PFS) and adverse events were evaluated across subgroups using descriptive statistics and survival analyses. Results: Between November 2012 and December 2020, 75 study sites recruited 210 patients treated with Axitinib (69,6% male; median age 69 years; median Karnofsky …Index 80%). Clear cell RCC was the most frequent histological subtype (81.0%). Axitinib was administered as second-line in 51.4%, third-line in 24.8%, and fourth-line treatment and beyond in 23.8% of the patients, respectively. MSKCC score was 15.0% favorable, 33.6% intermediate, and 51.3% poor risk. Median PFS was 5.6 months, and median OS 18.3 months. Patients with lactate dehydrogenase (LDH) levels > 300U/l had a nominally significantly shorter OS than patients with LDH≤300U/l (8.2 vs. 19.0 months, p  = 0.008). Drug related adverse and serious adverse events were reported in 56.7% and 17.6% of the patients, respectively (most common adverse event: gastrointestinal disorders; 37.6%). Conclusions: This real-world study confirms the clinical relevance of Axitinib in the second-line and beyond setting for a/mRCC with OS and PFS reported in concordance with pivotal trials, while demonstrating a favorable safety profile. A high LDH serum level could be a negative predictive marker for Axitinib effectiveness, which can aid in clinical decision making. Show more

Keywords: Renal cell carcinoma, Axitinib, survival, LDH, MSKCC score

DOI: 10.3233/KCA-220011

Citation: Kidney Cancer, vol. 7, no. 1, pp. 37-48, 2023

Authors: Cignoli, Daniele | Fallara, Giuseppe | Re, Chiara | Cei, Francesco | Musso, Giacomo | Basile, Giuseppe | Rosiello, Giuseppe | Salonia, Andrea | Larcher, Alessandro | Montorsi, Francesco | Capitanio, Umberto

Article Type: Systematic Review

Abstract: BACKGROUND: The influence of age and comorbidities during decision-making for patients with renal cell carcinoma remains controversial. OBJECTIVE: To comprehensively review the available evidence regarding the impacts of age and comorbidities on the decision to perform partial nephrectomy (PN). EVIDENCE ACQUISITION: A systematic review was conducted in accordance with PRISMA and registered with PROSPERO (CRD42022344759). Only randomized control trials, prospective cohort studies, registry-based studies, or single/multi-institutional retrospective cohort studies comparing PN to other therapeutic options for cT1N0M0 renal masses were considered. The primary outcome was to assess differences in patients’ baseline characteristics between different treatments in …order to investigate how those aspects have influenced clinical decision-making. Finally, perioperative outcomes were compared across the different options. EVIDENCE SYNTHESIS: Overall, patients who underwent PN were 3 to 11 years younger than those who underwent other treatments. Baseline renal function was slightly better in patients who underwent PN than in those who underwent radical nephrectomy (RN), active surveillance (AS), or tumor ablation. Patients undergoing PN had an average pre-treatment eGFR 4 to 6 points (mL/min/1.73 m2 ) higher than patients undergoing RN or tumor ablation. Likewise, the proportion of baseline chronic kidney disease (CKD) before treatment was higher in patients undergoing other treatments, with a rate of CKD between 6% and 56% higher compared with that for PN. A slightly higher proportion of baseline diabetes mellitus (DM) and cardiovascular comorbidities (CVD) were found in patients who underwent PN than in those who underwent RN (20% vs. 21% for DM and 37% vs. 41% for CVD). On average, patients who underwent AS and tumor ablation had more comorbidities, in terms of Charlson comorbidity index (CCI), DM, and CVD (50% vs. 38% for CCI ≥2; 25% vs. 20% for DM; and 43% vs. 37% for CVD). In terms of Eastern Cooperative Oncology Group (ECOG) Performance Status and American Society of Anesthesiologists (ASA) classification, no major differences were found between PN and other treatments, but a trend emerged whereby more fit patients underwent PN compared with RN (16% of ECOG >1 for PN vs. 18% for RN and 15% of ASA grade ≥3 for PN vs. 26% for RN). Again, tumor ablation was preferred for less fit patients (31% of ASA grade ≥3). No study included in our systematic review reported the baseline frailty status of patients treated for cT1 renal masses. The rates of perioperative complications and length of hospital stay (LOS) were similar between different techniques. CONCLUSIONS: Patients who underwent PN tended to be younger and fitter than those who underwent other available treatments for cT1 renal masses. Since this technique aims at reducing renal function impairment after surgery, a greater effort should be made to optimize patient selection to include more comorbid patients for whom PN might be useful. Show more

Keywords: Partial nephrectomy, age, comorbidity, frailty, renal function, kidney cancer, kidney surgery

DOI: 10.3233/KCA-230001

Citation: Kidney Cancer, vol. 7, no. 1, pp. 49-65, 2023

Authors: Brundage, James Nicholas | Sahu, Kamal Kant | Maughan, Benjamin Louis

Article Type: Systematic Review

Abstract: BACKGROUND: Papillary renal cell carcinoma (PRCC) has a relatively poor prognosis in the metastatic setting. In contrast to clear cell kidney cancer, there are limited treatment options specifically tested in PRCC. Alterations in the MET pathway are common in PRCC and may play a pivotal role in promoting tumor growth and the development of resistance to systemic therapy. OBJECTIVE: Current data on the efficacy of MET inhibitors over standard of care in PRCC is immature and evolving. The purpose of this systematic review is to assess and summarize the results and limitations of landmark trials of MET inhibitors …for PRCC as well as to discuss barriers faced by trials of these drugs. METHODS: Manuscripts and abstracts were collected from PubMed, the American Society of Clinical Oncology (ASCO) historical abstracts and European Society for Medical Oncology (ESMO) historical abstracts. Included studies must have been either a clinical trial, systematic review or narrative review and included PRCC patients. Patients must have been treated with a selective or non-selective MET inhibitor. After the final application of criteria, 30 studies were included. RESULTS/CONCLUSIONS: Cabozantinib has the best evidence for use showing improved outcomes in PRCC. Other MET inhibitors, including savolitinib, crizotinib, and foretinib have shown possible benefit in patients with MET-positive disease, but the inconsistent definition of MET status and a low patient accrual rate prevented further extrapolation of the individual trial results. Future trials of single agent savolitinib, as well as combination MET inhibitor/ immuno-oncology (IO) therapies, have the potential to change the therapeutic landscape of using MET inhibitors for PRCC. Show more

Keywords: MET inhibitor, renal cancer, papillary subtype, MET/HGF pathway

DOI: 10.3233/KCA-230005

Citation: Kidney Cancer, vol. 7, no. 1, pp. 67-80, 2023

Authors: Schindler, Nicholas R. | Braun, David A.

Article Type: Review Article

Abstract: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced renal cell carcinoma (RCC), but most patients still do not receive a long-term benefit from these therapies, and many experience off-target, immune-related adverse effects. RCC is also different from many other ICI-responsive tumors, as it has only a modest mutation burden, and total neoantigen load does not correlate with ICI response. In order to improve the efficacy and safety of immunotherapies for RCC, it is therefore critical to identify the antigens that are targeted in effective anti-tumor immunity. In this review, we describe the potential classes of target antigens, and …provide examples of previous and ongoing efforts to investigate and target antigens in RCC, with a focus on clear cell histology. Ultimately, we believe that a concerted antigen discovery effort in RCC will enable an improved understanding of response and resistance to current therapies, and lay a foundation for the future development of “precision” antigen-directed immunotherapies. Show more

Keywords: Renal cell carcinoma, tumor antigen, neoantigen, cancer vaccine, T cell receptor, chimeric antigen receptor T cell

DOI: 10.3233/KCA-230006

Citation: Kidney Cancer, vol. 7, no. 1, pp. 81-91, 2023

Authors: Parikh, Mamta

Article Type: Other

DOI: 10.3233/KCA-239002

Citation: Kidney Cancer, vol. 7, no. 1, pp. 93-94, 2023