Time to Treatment in Advanced Lung Cancer: A Quality Improvement Project Using Nurse Navigation and Liquid Biopsy

Abstract

BACKGROUND

Newly diagnosed patients with lung cancer experience significant challenges navigating a fragmented health system. Nurse navigators can use clinical expertise and coordination to address barriers to care.

OBJECTIVES

This quality improvement project aimed to expedite the selection and initiation of first-line treatment for patients with stage III or IV lung cancer. Using a nurse navigator process early on in care, coupled with liquid biopsy, this project focused on reducing the time from tissue biopsy to treatment decision.

METHODS

The team performed a retrospective chart review 12 months preimplementation and 8 months postimplementation.

FINDINGS

Using liquid biopsy, the time to treatment initiation was 21 days compared to 36 days with tissue biopsy only (p = 0.003). Postimplementation, median days to treatment decreased from 34 to 23.5 (p = 0.027), and treatment decisions made during the initial medical oncology visit increased from 38% to 55%.

LUNG CANCER REMAINS THE SECOND MOST DIAGNOSED CANCER in the United States (American Cancer Society, 2024). With rapid evolution in treatment modalities across oncology, it is imperative that oncology nurse navigators (ONNs) stay up to date on these modalities, tests, and guidelines to offer patients evidence-based care coordination and education. Patient understanding of the rationale and expectations behind various tests, as well as how they contribute to deciding the best treatment, is a key focus for ONNs (Oncology Nursing Society, n.d., 2017). Barriers for patients undergoing a complete workup can include lack of transportation to multiple appointments, financial barriers with co-pays or test costs, barriers to insurance coverage, anxiety, a lack of support, or other social determinants of health (SDOHs). ONNs can assess and provide proactive resources to address barriers, eliminating additional delays or hindrances to the clinical workup (Oncology Nursing Society, n.d., 2017).

Treatment modalities for lung cancer depend on numerous factors in the workup and can involve multiple specialties, including medical oncology, thoracic surgery, interventional pulmonology, and radiation oncology. In addition, positron-emission tomography scan, computed tomography scan, brain magnetic resonance imaging, or lung function tests (National Comprehensive Cancer Network [NCCN], 2023) guide the treatment decision-making process.

The most common lung cancer subtype is non-small cell lung cancer, which accounts for about 85% of lung cancer cases. With the advent of targeted therapies for lung cancer, molecular testing for tumor biomarkers is also an important part of the diagnostic workup (NCCN, 2023). The percentage of patients with lung cancer with actionable variants can vary. However, about 10%–15% of patients with non-small cell lung cancer have actionable variants (i.e., there are targeted therapies available to treat those specific variants). These variations often include alterations in genes such as EGFR, ALK, ROS1, and BRAF, among others. To date, 34 targeted therapies for lung cancer are approved by the U.S. Food and Drug Administration (National Cancer Institute, 2024). It is essential for patients with lung cancer to undergo comprehensive genomic testing to identify any actionable variants to determine the most appropriate treatment options (Chevallier et al., 2021).

Targeted therapies offer significant advancements in the management of lung cancer. The process of assessing the appropriateness of targeted therapies for treatment consideration involves conducting biomarker tests to identify tumor biomarkers (NCCN, 2023). However, obstacles can impede the testing process at various stages, most notably the length of time required to obtain test results. Current timing for biomarker tissue testing results is an average of 20–29 days (Choudhury et al., 2022; Eagle, 2023).

Biomarker tissue testing can be impeded by insufficient tissue specimens, repeated biopsies, the risk of depleting available tissue, the difficulty of accessing or the inability to access the area for tissue biopsy, cost, and a lack of infrastructure to send tissue samples for testing. These impediments offer insight into why fewer than 20% of patients with advanced lung cancer undergo complete biomarker testing when they are initially diagnosed (Eagle, 2023). All of these barriers may also contribute to delays in treatment or decision-making because of incomplete information (Aggarwal et al., 2021; Thompson et al., 2022).

The advent of liquid biopsy testing for circulating tumor DNA to evaluate for biomarkers can address many of the obstacles presented with tissue biomarker testing (García-Pardo et al., 2022; Rolfo et al., 2018). Liquid biopsy testing is completed with a peripheral blood sample and evaluates for circulating tumor DNA biomarkers recommended under NCCN guidelines for lung cancer (National Cancer Institute, 2020; NCCN, 2023; U.S. Food and Drug Administration, 2020). Liquid biopsy testing is approved by the U.S. Food and Drug Administration as a biomarker-testing method for stage III and IV lung cancer, and results are available in about seven days (Guardant Health, n.d.; National Cancer Institute, 2020). Liquid biopsy can test for the following biomarker point and deletion variants: KRAS, BRAF, EGFR, ERBB2, and MET. The following fusions can be tested with liquid biopsy: ALK, NTRK1, NTRK2, NTRK3, RET, and ROS1. Programmed cell death-ligand 1 can also be tested with liquid biopsy (Guardant Health, n.d.). In multiple studies of patients with lung cancer, tissue testing and liquid biopsy had 90% or more concordance in results (Choudhury et al., 2022; Thompson et al., 2022). Liquid biopsy testing is fully covered by Medicare and many private insurance companies, eliminating a cost barrier for patients or health systems, and it has been shown to be a cost-effective additional step for patients with advanced lung cancer (Ezeife et al., 2022; Guardant Health, n.d.).

Patients with advanced lung cancer (stage III or IV) often require urgent treatment to prevent progression (Mohammed et al., 2011; Mullin et al., 2020). However, delays in essential testing and evaluation can hinder healthcare providers from making well-informed and expedited treatment recommendations. These delays can lead to heightened patient anxiety, increased and prolonged patient distress, postponed treatment initiation, and the progression of disease (Mullin et al., 2020; Yang et al., 2023). Making decisions without full clinical data can also put patients at unnecessary risk for side effects or sequalae. If patients begin treatment and subsequent biomarker results reveal they received an unnecessary or contraindicated treatment type, this may affect later treatment choices and cause deleterious side effects with targeted therapy use (Calles et al., 2020; McCoach, 2019).

In 2022, at the Abramson Cancer Center at Pennsylvania Hospital (ACC PAH) in Philadelphia, 83% of thoracic oncology visits for lung cancer involved patients with an initial diagnosis of stage III or IV disease. The absence of a standardized process using nurse navigation and liquid biopsy testing resulted in many newly diagnosed patients attending medical oncology appointments without a complete workup, based on reports from the thoracic oncology providers. Consequently, patients were presented with various treatment options during their appointments, but providers lacked the necessary information to make a singular informed treatment recommendation. As a result, no definitive treatment decisions were made at the first visit, requiring a follow-up appointment once test results became available. These instances caused an inefficient use of provider and patient time, treatment and decision-making delays, increased co-pays, increased transportation difficulties, reduced patient comprehension, and heightened patient anxiety. The diagnostic components of lung cancer staging workup exist in an increasingly fragmented healthcare system, presenting barriers and confusion for patients (Byrne et al., 2020). Lack of timely and organized care coordination may contribute to delays in a patient receiving treatment (Byrne et al., 2020; Hunnibell et al., 2012; Kunos et al., 2015; Muñoz et al., 2018; Seek & Hogle, 2007; Zibrik et al., 2016). The use of ONNs has been shown to support improved care coordination for patients with cancer and decrease the time to treatment (Common et al., 2018; Hunnibell et al., 2012; Kunos et al., 2015; Seek & Hogle, 2007; Zibrik et al., 2016).

Purpose

This quality improvement project aimed to assess whether the implementation of a standardized procedure involving ONNs early on, combined with liquid biopsy testing, could reduce the treatment selection and initiation time for patients diagnosed with advanced stage III or IV lung cancer.

Methods

Project Design

The quality improvement project employed a single-center, retrospective, pre-/post-test design. One year of preimplementation data were compared to eight months of postimplementation data. The Plan-Do-Study-Act methodology was used to plan and direct the performance improvement efforts. The University of Pennsylvania Institutional Review Board assessed this project and determined that it qualified as a quality improvement project and did not require additional review.

Sample and Setting

This project took place at ACC PAH, which is a part of the University of Pennsylvania Health System. The outpatient oncology practice supports patients in the prevention, diagnosis, and treatment of cancer. In the 2022 fiscal year, the annual visit (new patient and returning patient) count was about 14,000 medical oncology visits, with about 4% being thoracic oncology specialist visits. The project was a collaborative effort among the interventional pulmonary section, thoracic oncology ONN and providers, thoracic disease team, quality improvement advisor, and administrative leaders.

The data collection included all adult patients aged 18 years or older who had stage III or IV lung cancer, were referred to ACC PAH, had completed biopsy testing, and whose treatment decision was selected between January 1, 2022, and August 31, 2023. Exclusion criteria included the following: patients who had stage I or II lung cancer, had selected another provider, had elected for hospice, had another diagnosis, had died prior to treatment, had been diagnosed previously, were seeking a second opinion, had no biopsy completed, were not treated, or were uninsured. The preimplementation period spanned from January 1 through December 31, 2022, and the postimplementation period spanned from January 1 through August 31, 2023. During this project, ACC PAH received 97 new referrals. The quality improvement team excluded 48 patients (see Figure 1), for a total of 49 included patients (N = 29 preimplementation; N = 20 postimplementation).

FIGURE 1.

QUALITY IMPROVEMENT PROJECT SAMPLE INCLUSION AND EXCLUSION FLOW DIAGRAM

Procedures

The team created a standardized workflow incorporating ONN interventions coupled with a standardized use of concurrent liquid biopsy at time of tissue biopsy. The interventional pulmonology provider referred patients with a suspected advanced lung cancer diagnosis to the ONN the same day as the interventional pulmonology evaluation visit that resulted in plans for tissue biopsy. The ONN initiated a process for patient contact along with care coordination, including arranging for concurrent liquid and tissue biopsy (see Figure 2).

FIGURE 2.

PREIMPLEMENTATION AND POSTIMPLEMENTATION PROJECT WORKFLOW

appt—appointment; IP—interventional pulmonologist; LB—liquid biopsy; ONN—oncology nurse navigator; SDOHs—social determinants of health

Note. Dashed lines indicate times when an ONN could become involved in a patient’s care. Preimplementation workflow could take 29–40 days, whereas postimplementation workflow could take as many as 8 days.

The ONN–patient follow-up telephone call included a navigation assessment evaluating SDOHs and educating the patient about the role of biomarkers in lung cancer and the liquid biopsy process in addition to tissue biopsy. Other diagnostic testing, such as positron-emission tomography or magnetic resonance imaging scans, were also coordinated by the ONN. At referral, the ONN held a medical oncology new patient appointment based on the estimated availability of diagnostic results. The ONN entered the liquid biopsy order online for the provider’s signature and ensured that the liquid biopsy testing kit was available in the operating room.

After the patient’s initial telephone call with the interventional pulmonologist for tissue biopsy results and diagnosis, the ONN called the patient, offered support, and confirmed previously attended medical oncology and radiation oncology appointments. The ONN placed any needed referrals to interprofessional departments to address any SDOHs barriers and made providers aware of SDOHs that could affect treatment. Prior to the medical oncology visit, the ONN monitored the liquid biopsy portal dashboard for results and ensured that results were distributed to all thoracic oncology providers.

Data Analysis

Preimplementation data were compared to postimplementation data. The team completed a retrospective electronic health record review for the patients who met inclusion criteria and entered the data into a database adherent to the Health Insurance Portability and Accountability Act. An independent review process ensured data entry accuracy.

The quality improvement team defined the time to treatment as the time from the date of diagnostic tissue biopsy to the selection date for the first-line treatment therapy (Thompson et al., 2022). For all patients, time to treatment involving a targeted oral therapy was measured by date of prescription for treatment initiation to account for variance in insurance factors for approvals and dispensing, which were outside of the control of this project. Overall liquid biopsy testing prior to or the same day as tissue biopsy was evaluated using descriptive statistics. Median time to treatment selection and initiation were evaluated for reduction between groups using a percentage change calculation and Mood’s Median Non-Parametric Hypothesis Test, a nonparametric test that compares the medians of two or more independent samples. The team measured overall and early referrals to ONNs, as well as the selection of first-line therapy at the first medical oncology visit using descriptive statistics and a percentage change calculation between groups. Mood’s Median Non-Parametric Hypothesis Test also determined the significance of ONN referrals and liquid biopsy testing on time to treatment selection and initiation. Use of liquid biopsy compared to tissue next-generation sequencing for first- and second-line therapies was measured using descriptive statistics. Days from biopsy to next-generation sequencing results as well as days from tissue biopsy to liquid biopsy results were measured using descriptive statistics.

Results

Demographic and clinical characteristics are reported in Table 1. The sample consisted of 49 patients, of whom 29 were women. Patients’ ages ranged from 53 to 90 years (X̄ = 68). Most patients (n = 29) were White and had a primary diagnosis of adenocarcinoma (n = 31).

TABLE 1.

PATIENT DEMOGRAPHICS AND CLINICAL CHARACTERISTICS (N = 49)

CHARACTERISTIC	X̄	SD
Age (years)	68	9.83
CHARACTERISTIC		n
Cancer stage (non-small cell) (N = 44)
IV		32
III		11
Classified as recurrence		1
Cancer stage (small cell) (N = 5)
Extensive		1
Unstaged		4
Diagnosis
Adenocarcinoma		31
Small cell		5
Squamous cell		9
Unspecified		4
Ethnicity
Hispanic and Latino		1
Non-Hispanic and non-Latino		48
Gender
Female		29
Male		20
Race
Asian		2
Black		17
White		29
Unknown		1

Liquid biopsy completion was shown to support a decrease in time to treatment initiation from 36 days to 21 days. Liquid biopsy completion also supported improved time to treatment selection from 19 days to 13 days (see Table 2).

TABLE 2.

NURSE NAVIGATION AND LIQUID BIOPSY EFFECTS ON TIME TO TREATMENT SELECTION AND INITIATION

VARIABLE	MEDIAN TIME TO TREATMENT SELECTION				p	MEDIAN TIME TO TREATMENT INITIATION				p
	NO ONN INVOLVED		ONN INVOLVED			NO ONN INVOLVED		ONN INVOLVED
	DAYS	n	DAYS	n		DAYS	n	DAYS	n
ONN referral per project pathway	35.5	2	14	47	0.132	42.5	2	29	47	0.141
VARIABLE	MEDIAN TIME TO TREATMENT SELECTION				p	MEDIAN TIME TO TREATMENT INITIATION				p
	NO LIQUID BIOPSY		LIQUID BIOPSY			NO LIQUID BIOPSY		LIQUID BIOPSY
	DAYS	n	DAYS	n		DAYS	n	DAYS	n
Liquid biopsy cases	19	24	13	25	0.085	36	24	21	25	0.003

ONN—oncology nurse navigator

Postimplementation, the use of liquid biopsy testing increased from 9 (N = 29) to 16 patients (N = 20), and the percentage completed prior to or on the same day as tissue biopsy use rose from 3 (N = 9) to 15 patients (N = 20). The median days from liquid biopsy sample collection to results was 7 days compared to 28 days for tissue test results (see Table 3).

TABLE 3.

DAYS FROM TISSUE BIOPSY TESTING RESULTS OR LIQUID BIOPSY RESULTS (N = 49)

VARIABLE	PREIMPEMENTATION (N = 29)			POSTIMPLEMENTATION (N = 20)
	X̄	MEDIAN	SD	X̄	MEDIAN	SD
Days from tissue biopsy to results	26.09	27	6.01	27.3	28	4.92
Days from liquid biopsy to results	11.78	10	6.48	7.31	7	3.08

An improvement was seen in overall referral to ONNs (8%) and in earlier referral to ONNs (14%) during this project; however, this improvement was not statistically significant. When an ONN was involved, the median days to treatment selection was 14 days compared to 35.5 days when an ONN was not involved. Involvement of an ONN affected earlier treatment selection and initiation. Overall treatment selection at the first medical oncology visit improved from 38% to 55%.

Discussion

ONNs function in a unique and necessary role for patients with cancer. Being one of the earliest contacts the patients have with the oncology interprofessional team, ONNs address patient barriers to care, including SDOHs that affect access to and timeliness and delivery of care. Research supports that patients with cancer who work with an ONN experience a reduced time from their diagnosis to treatment (Hunnibell et al., 2012; Kunos et al., 2015). This is most often seen with the effect of care coordination across a health system for testing and appointment scheduling (Byrne et al., 2020; Pautasso et al., 2018). Patients with cancer who receive help from an ONN also have documented improvement in their perception of involvement in care and knowledge about their treatment plan, as well as increased satisfaction and lower rates of distress (Loiselle et al., 2020).

ONNs address health system barriers using clinical and evidence-based practice to aid patients and the oncology interprofessional team in achieving timely access to care and treatment, as well as adherence to the testing and workups necessary to meet these goals (Peckham & Mott-Coles, 2018). Diagnosis and staging of lung cancer to determine treatment selection involves many testing modalities that are unfamiliar to patients and require care coordination across many departments. The evolution of treatments, such as immunotherapy and targeted therapies, necessitates biomarker testing as a recommended component of the staging and treatment determination workup (NCCN, 2023).

This project addressed barriers at the patient and process levels to reduce treatment time for patients with advanced lung cancer. The effects of early ONN involvement resulted in patients and providers determining treatment selection and initiation 21 days and 13.5 days sooner, respectively, than patients with no referral to an ONN. Although these data may not have been statistically significant, to any patient with an advanced stage of disease or their family members, reducing delays or wait times in choosing a treatment is clinically significant.

Recognizing that biomarker testing is recommended by NCCN guidelines for patients with adenocarcinoma and is strongly suggested for patients with squamous cell carcinoma, and with the current technology not allowing for rapid tissue molecular results, liquid biopsy testing can have a key role in receiving results sooner for a complete staging workup for patients with advanced lung cancer. Liquid biopsy testing is minimally invasive and cost-effective for patients, and can be easily incorporated into a standardized interprofessional workflow without significant disruption to patients, providers, or health systems. About 20% of liquid biopsy testing resulted in discovering actionable variants for first-line therapy. This is highly concordant with the actionable variants for first-line therapy identified from tissue biomarker testing (17%) in this study. Although tissue testing will remain the gold standard, the rapid turnaround time and high specificity of liquid biopsy testing has shown that oncology providers can have confidence in initiating targeted treatments without waiting on tissue testing results. Standardized use of liquid biopsies provided diagnostic results 20 days sooner, on average, and providers could better determine treatment plans earlier in the care continuum.

Limitations

There were several limitations to this project. The project leads and providers were unblinded to the objectives of this study, and it was conducted at a single center with a nonrandomized small sample size, limiting the generalizability and reflecting selection bias. Inclusion criteria were limited, and uninsured patients were excluded from the study, although these patients may have had different results with the added barrier to care. Internal validity may have been influenced by confounding variables, such as the time to schedule imaging studies or the first medical oncology visit. SDOHs, including transportation barriers, may influence a patient’s ability to attend appointments scheduled on short notice. In addition, when patients were prescribed an oral treatment, the prescription date was used as the treatment initiation date. This may not reflect the date when treatment started because of variables beyond project control (e.g., insurance clearances, specialty pharmacy delivery timelines); however, the project scope did not contain interventions applicable to these variations. For the purposes of data analysis, this measure was the same across the pre- and postimplementation groups. The results were not normally distributed, resulting in limited options for statistical analysis methods.

Although not measured within the scope of this project, expediting the completion of all workup testing before initial medical oncology appointments could streamline discussions about treatment choices. This approach aims to provide a more focused dialogue between patients and providers, reducing information overload and enabling conversations about treatment effects and goals of care. Future studies should include a larger sample size and more than one location for generalizable results.

Implications for Nursing

Proactive engagement and early intervention of ONNs can facilitate the coordination of tests, address access barriers, and serve as a valuable resource for patients, families, and the interprofessional care team, all of which can help to expedite treatment selection and initiation. Oncology nurses and ONNs have a role in identifying and facilitating oncology workup and treatment plans that adhere to best practices, including understanding the role of biomarker testing and its results. Liquid biopsy testing completed at the time of tissue biopsy can expedite the identification of first-line treatment options and accelerate the initiation of treatment. By involving ONNs earlier, all diagnostic tests are coordinated and the time to treatment is improved. ONNs are integral to identifying barriers, gaps, and areas for process improvement among interprofessional oncology teams, enhancing patient care and outcomes.

Conclusion

In a patient population with high anxiety because of a potentially life-limiting diagnosis, time to treatment decision and initiation is crucial for the patient experience and disease outcome. Providers and health systems can recognize and use available resources that will result in patients receiving needed treatments sooner.

Research continues to document the improved experience of treatment and time initiation for patients who receive assistance from an ONN. However, early ONN involvement, paired with a standardized process for liquid biopsy completed simultaneously with tissue biopsy testing, demonstrates an even greater reduction in time to treatment selection and initiation. With early involvement, ONNs can educate patients about liquid biopsy testing and facilitate the interprofessional coordination needed to ensure the timing of its completion. If liquid biopsy testing is not performed at the time of tissue biopsy, ONNs can facilitate this testing initiation prior to a patient’s first medical oncology visit.

Nurse navigation often focuses on assessing and addressing patient barriers to care, but it also focuses on system-level barriers beyond care coordination or appointment scheduling. Recognizing evolving and best practices, ONNs can influence processes, educate patients about those processes, and achieve better outcomes for patients and health systems. Most discussions on SDOHs focus on patient-level metrics; however, health systems also have their own SDOHs based on location, access to resources (e.g., in-house advanced testing capabilities), and staffing challenges among specialties. Using ONNs and liquid biopsies can enhance patient- and health system–level resources to provide access to the highest level of care in a more timely and efficient manner.

IMPLICATIONS FOR PRACTICE.

• ■ Facilitate the coordination of tests, address access barriers, and serve as a valuable resource for patients, families, and the clinical care team early on in the cancer care continuum to expedite determining treatment plans.

• ■ Perform concurrent liquid biopsy testing at the time of tissue biopsy to quicken the identification of first-line treatment options and accelerate the initiation of treatment.

• ■ Optimize patient care via nurse navigation by combating barriers caused by social determinants of health, while simultaneously addressing health system barriers using evidence-based practice and clinical expertise.

PROFESSIONAL DEVELOPMENT ACTIVITY.

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Consider how you can apply findings from this article to your own practice using the following questions:

• ■ How could the implementation of nurse navigation and liquid biopsy testing improve the time to treatment initiation for patients in your healthcare setting, and what specific barriers might you need to address to achieve similar results?

• ■ Reflecting on the challenges and delays in treatment decision-making highlighted in the article, what strategies could you adopt to streamline diagnostic processes and ensure timely and informed treatment decisions for your patients or team?