IKCS 2022: Quality of Life and Systemic Therapy for Renal Cell Carcinoma

(UroToday.com) The 2022 IKCS North American annual meeting featured a session on side-effect management and quality of life perspectives in kidney cancer treatment, including a presentation by Dr. Elizabeth Wulff-Burchfield discussing quality of life and systemic therapy for renal cell carcinoma (RCC). The World Health Organization defines quality of life as “an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.” Dr. Wulff-Burchfield notes that health-related quality of life narrows the multidimensional concept of quality of life into a focus on one’s health and the ways it contributes, positively or negatively, to well-being. Groundbreaking work by Priestman and Baum in 1976 demonstrated the feasibility and value of collecting serial patient rating of quality of life while on chemotherapy, demonstrating that side effect burden can decrease serial measurement for patients receiving cytotoxic chemotherapy for advanced breast cancer. Importantly, health related quality of life is now considered a crucial component (in addition to efficacy) when defining value of cancer treatment.

There are several reasons why health related quality of life matters:

Ethical – longevity matters if the person experiencing it considers their well-being to be acceptable
Practical – tolerance for medical burden and potential for benefit exists on a spectrum, and understanding the quality of life implications of different interventions or treatment regimens will help support evidence-based decision-making
Scientific – in RCC, data clearly indicates that health related quality of life is a biomarker for improved cancer outcomes during treatment with cytokine therapy, VEGF TKIs, and immune checkpoint inhibitor therapy. In advanced cancer, protocols that assess patient-reported outcomes and rigorously mitigate symptoms are associated with improved overall survival.

Dr. Wulff-Burchfield notes that in clinical trials, patient reported outcome measures are the primary source of health related quality of life data. This includes any report made by the patient to reflect their health functional status, symptoms, quality of life, or other domains outside (ie. clinician) interpretation. In clinical trials, patient reported outcomes include validated questionnaires, which are often specific to the patient population being studied. While quality of life is unavoidably subjective, use of patient reported outcome measures standardize reporting and allows for further analyses beyond simple comparisons of global health related quality of life (ie. quality-adjusted life years, etc). In trials of interventions of RCC, commonly selected measures include the following, which allow for comparisons across regimens, disease states, and disease stages:

EORTC QLQ-C30
FKSI-19
FACT-G
EQ-5D-5L (or 3L)

At ASCO 2022, Dr. Cella and colleagues presented data on the relationship between health related quality of life and clinical outcomes in patients with advanced RCC in CheckMate 214 [1], which was an analyses investigating the prognostic value of health related quality of life data as a clinical biomarker. Cox proportional hazards models were applied to time to event data assessing baseline and longitudinal outcomes, including FKSI-19 total score and disease related symptoms subscale. As follows highlights health related quality of life as a biomarker affecting PFS and OS:

Furthermore, a landmark analysis for overall survival differentiated patients who were health related quality of life responders versus non-responders. Responders were defined as having an improvement in FKSI-19 total score by >=5 points or decline by <=5 points, whereas non-responders were defined as having worsening FKSI-19 total score by >=5 points. In a pooled analysis of all patients, HR was 0.48 (p < 0.001) for health related quality of life responders, which was also confirmed in each separate arm of the trial: nivolumab + ipilimumab HR 0.39 (p < 0.0001) and sunitinib HR 0.57 (p < 0.0001). Of note, Dr. Wulff-Burchfield states that a similar analysis has been performed in CheckMate-9ER and with almost identical findings in that quality of life (both baseline and longitudinal) is an excellent biomarker for OS and PFS.

In addition to patient reported outcomes, other data from trials and/or practice can help complete the picture of health related quality of life associated with systemic therapy regimens. This may include:

Continuous toxicity or limited/intermittent toxicity
Dose reductions
Treatment interruptions
Premature discontinuation of treatment
Frequency of treatment – time-related burdens of care (“time toxicity”), which is under-recognized but can significantly detract from patient and/or caregiver quality of life
Possibility of treatment-free survival

As follows is table comparing quality of life data for frontline regimens in CheckMate 214 [1], KEYNOTE-426 [2], CheckMate-9ER [3], and CLEAR [4]:

Dr. Wulff-Burchfield notes that “The Great Debate” is: Why focus on health related quality of life and toxicity data up front? Why not just choose treatment solely on efficacy and/or disease related factors and titrate the agents to mitigate toxicity? She notes that titration may be unavoidable, but the need for titration means that patients are experiencing grade 3-4 toxicity (or unacceptable grade 2 toxicity). This detracts from patient well being, disrupts work, and undermines their functional status. Additionally, this can start a cascade towards debility and increasing burden on the caregiver. Patient centeredness also must acknowledge that goals and motivations of patients may vary and that longevity may not be the primary goal of all patients.

Elucidating your patient’s goals of care and tolerance for medical burden is the key to understanding how to apply health related quality of life/toxicity data into treatment decisions. However, this is a challenging task in the clinic, particularly for new patients, second opinions, and consultative practices. One framework to use is REMAP as highlighted by the following:

R – Reframe the headline of the medical narrative by starting with “I think that” or “It’s worrisome that”

E – Expect emotion and allow space for emotion by acknowledging it

M – Map patient values

A – Align with the patient by summarizing your understanding the patient’s stated values as they intersect with healthcare

P – Propose a plan by synthesizing your understanding about outcomes, toxicity, and patient goals

Dr. Wulff-Burchfield notes that mapping values crystalizes a patient’s beliefs, fears, and goals of care. There are several strategies that are applicable when considering integration of quality of life into the decision making process:

Asking about values directly – “what is most important to you when you consider cancer care?”
Exploring worries – “as you think about embarking on treatment, is there anything specific that worries you?”
Reflecting on emotion – “you had so much emotion in your expression when you talked about wanting to see your son graduate from law school. Would you say that your main focus is for treatment to help you live as long as possible?”

Patients stated values can help signal that they are (or are not) willing to risk significant medical burden. Typically, patients with a primary focus on longevity are willing to risk more medical burden, but this is highly personal. While efficacy outcomes and disease-related factors are the primary basis for clinical decision-making, health related quality of life data are crucial factors to incorporate into shared decision-making regarding treatment. Understanding and incorporating your patients’ perspectives regarding treatment goals and tolerance for medical burden will ensure optimal treatment selection and patient-centeredness:

Dr. Wulff-Burchfield concluded her presentation discussing quality of life and systemic therapy for RCC with the following take home messages:

Health related quality of life associated with systemic therapy is a multidimensional component and an essential component to shared-decision making for RCC treatment
The REMAP framework can help with assessing patient’s values in order to determine their goals of care and willingness to risk medical burden from their treatment regimens

Presented by: Elizabeth Wulff-Burchfield, MD, University of Kansas Medical Center, Kansas City, MO

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 International Kidney Cancer Symposium (IKCS) North America, November 4-5, Austin, Texas, USA

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