Early-phase trials, particularly phase I studies, occupy a distinctive position in oncology. They are designed primarily to evaluate the safety, dosing, and preliminary activity of investigational agents rather than to establish definitive efficacy, and the patients who enroll in them typically have advanced disease that has progressed through standard therapies. Historically, some clinicians worried that frank discussions about goals of care and end-of-life preferences might undermine patients’ hope or their willingness to participate in research. That assumption has been increasingly challenged. Guidelines from the American Society of Clinical Oncology, updated in 2024, recommend that palliative care be integrated alongside active cancer treatment for patients with advanced cancer, and the European Society for Medical Oncology has similarly emphasized advance care planning as a core component of palliative care practice since its 2014 clinical practice guidelines on the subject.

Advance care planning encompasses a spectrum of activities: conversations in which patients articulate their values and preferences for future care, the designation of a healthcare proxy or surrogate decision-maker, and the formal documentation of those preferences in advance directives or medical orders. In the context of early-phase trials, planning takes on particular significance. Patients in these studies face inherent uncertainty about whether an experimental agent will benefit them, and trial protocols can impose demanding schedules of visits, imaging, and laboratory monitoring. When serious adverse events or disease progression occur, patients and families who have already discussed their priorities may find it easier to make consequential decisions about whether to continue on protocol therapy, transition to hospice, or pursue other options.

The original study that prompted the correspondence, conducted by a team including researchers at a major oncology center and published in Supportive Care in Cancer in January 2026, investigated the use of supportive care services and advance care planning among early-phase oncology clinical trial participants. Supportive care in this setting spans a wide range of services: palliative care consultations, pain management, psychological and psychiatric support, social work services, nutrition support, and symptom-directed interventions that run alongside the experimental treatment. The study’s central finding, as characterized in the correspondence, is an association between the use of these services and advance care planning, raising the question of what that association actually means and how it should be interpreted.

Xue and Yan’s commentary focuses precisely on this interpretive challenge. An observed association between two clinical behaviors does not by itself reveal the direction of causation, and the authors underscore that several explanations are plausible. One possibility is that engagement with supportive care services creates natural opportunities for advance care planning discussions. Palliative care clinicians, social workers, and other supportive care professionals are trained to elicit patient values and to facilitate conversations about future care, so patients who connect with these services may simply have more structured occasions to formalize their preferences. In this framing, supportive care acts as a gateway that normalizes and operationalizes planning conversations that might otherwise never occur in the busy environment of a phase I clinic.

An alternative interpretation runs in the opposite direction: patients who have already engaged in advance care planning may be more receptive to supportive care services, or their clinicians may be more likely to refer them. A patient who has documented preferences and articulated goals may signal to the care team that supportive care involvement would be aligned with their wishes. Selection effects may also be at work, since patients who are more engaged, more health-literate, or more trusting of the medical system may be more likely both to accept supportive care referrals and to complete planning documentation. The correspondence emphasizes that disentangling these possibilities matters, because the practical implications differ depending on which mechanism predominates.

The clinical stakes of this interpretive question are considerable. If supportive care use genuinely promotes advance care planning, then interventions that expand access to palliative and supportive services in early-phase trial populations could yield benefits that extend beyond symptom control, improving the alignment of care with patient values at the end of life. Prior research summarized in the surrounding literature supports this possibility. A 2024 review in Cancer Treatment Reviews examined the role of palliative care in optimizing early-phase cancer trials, and work published in Current Problems in Cancer in 2023 addressed the integration of palliative care for patients on phase I trials. An Australian single-center study published in Cancers in 2025 documented advance care planning practices specifically in early-phase trial participants, adding international perspective to a conversation that has been dominated by United States-based cohorts.

The correspondence also speaks to a persistent documentation gap. Advance care planning that occurs in conversation but is never recorded in the medical record has limited utility when patients deteriorate acutely, because clinicians who are unfamiliar with the patient cannot act on undocumented preferences. Studies across oncology settings have repeatedly found that documentation rates lag well behind the frequency of discussions, and early-phase trial populations are no exception. Xue and Yan’s commentary implicitly argues that researchers and clinicians should attend not only to whether planning occurs but to how it is captured, communicated, and honored across the multiple teams involved in trial care, including research coordinators, treating oncologists, hospitalists, and emergency personnel who may encounter these patients during acute events.

For trial design and clinical operations, the message is that supportive care and research participation should be viewed as complementary rather than competing. The traditional concern that palliative care involvement might depress trial enrollment or blur the assessment of investigational agents has not been borne out in the literature; instead, integrated models appear to support patients through the demands of protocol participation while safeguarding their broader goals. The correspondence’s authors, writing from a radiotherapy department in a Chinese provincial hospital, bring a perspective that highlights the global relevance of these questions, since norms around end-of-life communication vary across health systems and cultures, and the infrastructure for supportive care differs markedly between high-resource trial centers and other settings.

Ultimately, the correspondence by Xue and Yan serves as a reminder that the statistical association between supportive care use and advance care planning in early-phase trial participants is a starting point for inquiry rather than a conclusion. Understanding whether supportive services catalyze planning, whether planning opens the door to supportive care, or whether both reflect an underlying orientation toward proactive, values-concordant care will require longitudinal designs, careful measurement of the timing of each behavior, and attention to the conversations that connect them. What is already clear is that patients who volunteer for early-phase trials are not exempt from the need for thoughtful planning about their future care, and that the clinical teams who run these trials are well positioned to ensure that supportive care and advance care planning travel together as standard practice rather than as afterthoughts.

Subject of Research: The association between supportive care service use and advance care planning among early-phase oncology clinical trial participants

Article Title: Interpreting the association between supportive care use and advance care planning in early-phase trial participants

Article References: Interpreting the association between supportive care use and advance care planning in early-phase trial participants. (n.d.). https://doi.org/10.1007/s00520-026-11295-5

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11295-5

Keywords: advance care planning, supportive care, palliative care, early-phase clinical trials, phase I oncology, cancer patients, end-of-life care, clinical trial participants, patient preferences, oncology guidelines, documentation, correspondence

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Subject of Research: EGFR-mutated non-small cell lung cancer (NSCLC), bispecific antibody-drug conjugate therapy

Article Title: Early Clinical Results Highlight Iza-bren’s Promise in Treating EGFR-mutated NSCLC

News Publication Date: September 6, 2025

Web References: www.iaslc.org

Keywords: Lung cancer, EGFR mutation, non-small cell lung cancer, antibody-drug conjugate, bispecific antibody, HER3, topoisomerase I inhibitor, targeted therapy, iza-bren, BL-B01D1, clinical trial, phase I/II trials