Prehabilitation is the Gateway to Better Functional Outcomes for Individuals with Cancer

Abstract

Prehabilitation is a clinical model that introduces components of rehabilitation to patients prior to undergoing intensive medical interventions, such as surgery, in order to optimize function and improve tolerability to the intervention. Cancer care introduces a continuum of sequential or concurrent intensive anti-neoplastic medical interventions that are known to be detrimental to a patient’s function. Prehabilitation evidence has grown across several areas of oncology care delivery demonstrating that a multi-modal rehabilitative intervention, delivered prior to oncology-direct therapies, leads to better functional outcomes and improves important endpoints associated with surgery and cancer treatment. This commentary article provides a brief history of the emergence of prehabilitation in cancer care delivery, reviews the current evidence base and guidelines for prehabilitation, and offers insights for future implementation of this model as a standard in oncology care. A prehabilitation program is an optimal starting point for most patients undergoing anti-neoplastic therapy as it serves as a gateway to improving functional outcomes throughout the cancer continuum. Future research in prehabilitation should aim to reach beyond measuring functional outcomes and to explore the impact of this model on important disease treatment endpoints such as tumor response to oncology-directed treatment, impact on treatment-related toxicities, and disease progression.

Introduction

Cancer prehabilitation is defined as a “process in the cancer continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment and includes physical and psychological assessments that establish a baseline functional level, identify impairments, and provide interventions that promote physical and psychological health to reduce the incidence and/or severity of future impairments.”¹ Prehabilitation, as a model of care in rehabilitation, evolved from getting soldiers physically and emotionally ready for combat.² Physicians recognized that helping patients get stronger before an upcoming stressor, such as surgery, would likely help to decrease morbidity and mortality. Evidence of prehabilitation models is found across medicine in orthopedics and sports medicine, cardiac care, as well as cancer. Thus, for decades prehabilitation has been documented in the medical literature with more exponential growth recently focused on cancer. (Figure 1a and 1b).

Figure 1a and 1b -.

PubMed database yearly change in publications using “prehabilitation” as the search term

Since the United States (US) passed the National Cancer Act of 1971, US medical institutions have significantly expanded their infrastructure for providing high quality cancer research. Following this milestone, advancements in drug development and technology escalated and improved cancer care outcomes so significantly that a new issue of cancer survivorship came into focus and required further attention. In 1999, the National Cancer Institute, which is part of the federally funded National Institutes of Health, established the Office of Cancer Survivorship which brought into sharp focus, the needs of this growing segment of the population. Over the last two decades the enhanced emphasis on survivors’ functional outcomes has led to a growing evidence base in oncology rehabilitation³ as well as policy initiatives aimed at improving access to high quality cancer care^{4, 5} and survivorship supportive care services⁶, in an effort to improve long-term survivorship. Prehabilitation has featured prominently in this dialogue.⁷

Prehabilitation in oncology

Prehabilitation is introduced to the cancer care delivery continuum in a variety of ways under many different clinical scenarios. For example, while most of the literature has focused on prehabilitation prior to surgery, these interventions may also support the health and well-being of patients who are anticipating non-operative oncology directed therapies such as neoadjuvant chemotherapy or first line targeted agents.⁸ Single modality prehabilitation, frequently utilizing either exercise or nutritional interventions have been commonly employed; however, research suggests a multi-modal approach may be more effective.^9-11 For example, exercise combined with nutrition interventions, smoking cessation, stress reduction, and other modalities are beneficial.¹² Prehabilitation fits nicely into the care continuum as a component of early recovery programs such as enhanced recovery after surgery (ERAS) protocols which are implemented during the peri-operative period.¹³

The evidence base in oncology has developed primarily across three common disease types: gastrointestinal cancers, lung cancer and hematologic malignancies. Program examples in colon cancer emphasize multi-modal interventions and demonstrate improvement in functional outcomes as well as peri-operative outcomes.^14-17 Prehabilitation programs in lung cancer demonstrate functional status improvements in patients deemed high-risk or poor surgical candidates. Improving pulmonary function and walking tolerance through prehabilitation enhances the patient’s performance status and ability to tolerate surgery and adjuvant therapies.^{18, 19} Prehabilitation is also feasible for individuals prior to hematopoietic stem cell transplant (HSCT), with high adherence to exercise prescription and improved self-reported quality of life, blood count markers, and fatigue reported.²⁰ Exercise outcomes are optimized when started before the transplant, as with a prehabilitation program.²¹ While these examples provide evidence for the impact of prehabilitation on overall physical performance and function, there are also myriad clinical examples that demonstrate improvements in impairment and reduced functional morbidity when prehabilitation interventions are used. Examples include reducing post-operative incontinence and loss of muscle mass through prostate cancer prehabilitation^22-25 and enhancing upper quadrant function and preventing chronic lymphedema in breast cancer.^26-28

Additional evidence supports that prehabilitation impacts cancer treatment-related surgical mortality among frail and elderly patients,^{29, 30} and may assist with addressing worsening health status due to factors related to the COVID-19 infection and sequelae among individuals with cancer.³¹

Leveraging prehabilitation models to integrate rehabilitation in cancer care

Rehabilitation medicine is a specialty traditionally focused on improving quality of life (QOL) in terms of improved independence and functional performance. The emphasis on QOL outcomes such as function may be a contributor to cancer rehabilitation’s chronic problem of under-referral from oncology services^32-34 as the outcome oncology specialists are typically most concerned with is survival. Oncologists often center their attention on restaging examinations and tumor markers while issues like cancer-related fatigue, chemotherapy induced peripheral neuropathy, or musculoskeletal dysfunction may receive less attention.

The traditional model for cancer rehabilitation integration into oncology care is reactive, when cancer and cancer treatment-related impairments are identified often months or years after diagnosis, leading to later rehabilitation referral. This model may lead to missed opportunities for preventive cancer rehabilitation and earlier rehabilitation involvement to maintain function and reduce cancer related symptoms.

Prehabilitation has garnished increasing interest amongst oncology clinicians because its ultimate goal speaks to what most oncologists and surgeons are focused on: improving survival. Outpatient prehabilitation consults at MD Anderson Cancer Center have increased more than 200% over the past four years and currently account for approximately 50% of new physiatry outpatient consults ⁱ. The prehabilitation program started with pancreatic cancer through gastrointestinal surgical oncology referrals and focuses the intervention prior to Whipple procedures. This service has grown to include hematopoietic stem cell transplants and most recently chimeric antigen receptor T-cell (CAR-T) therapy patients.

Summary

Although prehabilitation has been incorporated into some clinical practice guidelines and other authoritative reports,^35-37 there are still many gaps in the science and recommendations.⁹ Nevertheless, prehabilitation involves an important set of clinical interventions which can not only improve physical, psychological, and functional outcomes but also may be cost effective¹⁰ and amenable to use with new technologies in virtual care.³⁸

We believe that the rapidly growing field of prehabilitation should be embraced by professionals across rehabilitation medicine and in oncology. The expertise of rehabilitation professionals in neuromusculoskeletal conditions, including an understanding of physical impairment and function and skilled interventions in remediating functional limitation for the medically complex individual with cancer make us an optimal member of the oncology care team. However, integration of prehabilitation into oncology care will require a different and more proactive engagement of the rehabilitation professional. Because of the rapidly growing survivor population and the substantial and growing burden of their functional needs, early referral to prehabilitation and rehabilitation services should become a standard in the cancer care continuum. There is great opportunity for early cancer rehabilitation involvement and follow patients throughout Dietz’s stages of cancer rehabilitation³⁹ perhaps under a prospective surveillance care model.⁴⁰ Prehabilitation introduces the concepts of function and exercise to the patient at diagnosis and serves as the gateway to better functional outcomes for individuals with cancer.