What Is the Clinical Course of Advanced Solid-Tumor Cancers?

Introduction and Scope of the Problem

Although the National Cancer Institute (NCI) defines advanced cancer as “unlikely to be cured or controlled by treatment,” recent advances in therapy have favorably altered the illness trajectory for patients with many types of cancer. The overall rate of cancer-related deaths in the United States decreased by 15% from 2007 to 2017 and by an average of 1.5% per year from 2013 to 2017. This decrease in mortality is due in part to a reduced incidence of smoking-related cancers, but it is also due to the availability of more effective cancer therapies leading to longer survival ( Fig. 36.1 demonstrates these mortality trends in lung cancer). For example, survival among women with advanced breast cancer improved from 21 months in 1990 to 38 months in 2010. This improvement is associated with the introduction of new treatments such as paclitaxel, trastuzumab, and aromatase inhibitors. Improvements in survival have not been uniform across all cancers. Survival rates among certain poor-prognosis advanced cancers, such as pancreatic cancer and soft tissue sarcomas, have remained stagnant (though recent advances in the management of locally advanced pancreatic cancer have shown promising results). The overall gains in survival across many cancer types have led to a growing population of metastatic cancer survivors.

Illness experience and survival vary widely across patients with advanced cancer based on a number of disease-specific, patient, and health system-level factors. Similarly, aggressiveness and treatment sensitivity differ across cancer types and within subtypes of the same cancer: cancers may be slow growing and require only surveillance; they may progress quickly, with short intervals between lines of cancer treatment; or they may exhibit a range of behavior in between these two ends of the spectrum. Among patients with the same cancer type or subtype, outcomes vary based on comorbidity and functional status due to both the prognostic significance of these factors and their impact on the patients’ ability to receive and tolerate cancer therapy. Finally, health system–level issues such as systemic racism and a lack of health insurance affect patient outcomes through variation in access to timely and high-quality care. Patients who live in rural areas also experience disparities in cancer treatment due to a paucity of specialists and decreased access to clinical trials. Evidence from clinical trials can give clinicians and patients insight into how tumor biology and responsiveness to treatment will affect patients’ trajectory, but the limited representation of patients with impaired performance status and from diverse racial backgrounds and socioeconomic circumstances limits the ability to generalize from clinical trials to the general population.

A growing body of evidence supports the integration of palliative care into oncology care throughout the cancer trajectory to improve patient and family caregiver outcomes for patients with a serious cancer diagnosis. Several clinical trials have demonstrated that palliative care improves patients’ quality of life and mood symptoms, increases advance care planning, and decreases health care utilization at the end of life when integrated with oncology care. As patients live longer with advanced cancer and the growing demand for palliative care clinicians continues to exceed the supply, the optimal timing and frequency of palliative care involvement remains an important area of investigation, resulting in a clear need for all clinicians who care for patients with advanced cancer to gain proficiency in core palliative care skills.

In addition to providing symptom management and psychosocial support, palliative care specialists help patients and families understand what to expect from their cancer so that they may plan for the future. Given the ever-changing landscape of oncology care, palliative care clinicians should not be expected to become experts in the management of all kinds of cancer. Rather, collaboration with oncology teams is critical—specifically, the exchange of salient information to support patients and families in understanding their prognosis and the expected illness trajectory, and in making major decisions. This chapter describes general phases of the advanced cancer trajectory, including diagnosis, treatment, surveillance, and transitions as well as the transition to end of life. It also provides recommendations for the integration of palliative care into the illness trajectory, along with suggested topics for palliative care clinicians to discuss with oncology clinicians to mutually inform their care of individual patients (see Table 36.1 ).

Relevant Pathophysiology

Patients with advanced cancer generally come to medical attention due to symptoms, as opposed to screening such as mammography and colonoscopy, which more commonly detect precancerous or early-stage lesions. Common presenting symptoms of advanced cancer are shown in Fig. 36.2 . Radiographic imaging (such as by X-ray, ultrasound, computed tomography, or magnetic resonance imaging) helps clinicians detect and localize cancers; however, a definitive diagnosis usually requires pathological evaluation of a biopsy sample. Molecular diagnostics, involving evaluation of tumor DNA either from tumor biopsies or from circulating tumor DNA detected in the peripheral blood, are an increasingly important component of the selection of initial diagnostic evaluation and treatment. In addition to defining the cancer type with a biopsy, determining the cancer stage is an important part of the diagnostic workup. The stage of most solid-tumor cancers is determined by the primary tumor size, number of lymph nodes affected, and presence of distant metastases (the TNM staging system). Brain tumors do not follow a staging system, but rather are graded in stages I through IV. The stage and molecular features of a cancer help the oncologist estimate a patient’s prognosis and formulate a treatment plan.