The concept of prehabilitation is as old as humanity. Physical, psychological, and emotional training improves tolerance to subsequent stressors. This has been true in hunting communities in the Pleistocene, and still is for sporting events or performances today. The stimulatory effects of low‑dose insults, termed hormesis, has entered our understanding as a fundamental biphasic dose‑response present in many biological systems.¹ Thus, small insults prepare organisms to withstand more severe ones.

The term prehabilitation was introduced in the 1940s, and first appeared in a scientific journal when the British Army developed a prehabilitation program as part of an experiment to increase the quality of young recruits.² The program remarkably increased the recruits’ physical health and intellectual capacity.³ After being forgotten, these ideas resurfaced in the 1980s and programs of preoperative training and support were developed to decrease complications in patients undergoing major orthopedic, thoracic, and abdominal surgery. In the following decades, an increasing number of prehabilitation trials has been published, including studies preparing oncological patients for surgery, and, in some instances, for radiotherapy or systemic anticancer therapies.

In 2011, the first systematic review reported on 11 randomized controlled prehabilitation trials,⁴ and in the following years multiple systematic reviews and meta‑analyses as well as umbrella reviews targeting different aspects of the topic have been published. All reviews agreed that the methodological quality of prehabilitation studies is low, still allowing only cautious conclusions about the benefits of these programs. Four recent meta‑analyses focusing on different surgical populations, and each including more than 1200 patients, arrived at similar conclusions, agreeing that prehabilitation programs decrease hospital length of stay (LOS) by around 1 day, decrease complication rates by 40%–50%, and improve quality of life and 6‑minute walking distance.^5-8 The largest of these 4 meta‑analyses, including 186 randomized controlled trials (RCTs) and 15 684 participants, compared prehabilitation based on 1) nutritional support, 2) exercise, 3) exercise plus nutritional support, and 4) trimodal combined exercise, nutritional, and psychosocial support.⁸ The authors reported that all types of programs decreased LOS and complication rates, but that all findings were based on very low certainty of evidence. Interestingly, findings remained robust when trials with a high risk of bias were excluded.⁸

Since implementing a rehabilitation program requires considerable resources, the lack of high‑certainty evidence (and lack of reimbursement) has led to the development of lower‑cost home‑based rehabilitation programs based on a reduced number of patient education sessions. A recent review and meta‑analysis included 29 home‑based prehabilitation trials with 3508 patients and observed decreases in postoperative complication rates (by 16%) and LOS (by 0.3 days), though to some lesser degree than in‑hospital prehabilitation. Interestingly, the authors also detected significant improvements in depression and anxiety scores.⁹

Considering these results, the plausibility of the prestress training concept is somewhat weakened by the difficulties, even with a large and growing evidence base, to reach medium or high certainty of evidence supporting mono-, bi-, or trimodal prehabilitation programs. Calabrese et al¹⁰ concluded that the magnitude of hormetic effects, while present, is modest, and in the percentage range, not fold, making it not easy to assess. Certainly, there are a number of problems and heterogeneities in trial designs and methodological quality to be found in the accumulated data on prehabilitation. These include differences in the type of surgery, patient condition (eg, age, performance index, diagnosis, cancer stage, comorbidities, degree of malnutrition, or cachexia), type of intervention (nutrition and / or exercise, psychosocial support, timing pre- / peri- / or postsurgery, duration, intensity, compliance), and choice of an adequate control. Overall methodological quality depends on the risk of bias arising from the randomization process, protocol deviations, missing outcome data, measurement of the outcome, and selection of the reported results.¹¹ In combination, low methodological quality and large heterogeneity in trial designs contribute to the present unsatisfactory situation.

In these circumstances, it is difficult to draw new significant conclusions out of the available data without access to new and better designed and executed trials. However, in this issue of Polish Archives of Internal Medicine, Grońska et al¹² try to rise to this challenge. They present a systematic review of 12 studies, with 10 RCT and 2 observational studies (1 with a historical, the other without a control arm). The trials were performed in patients with cancer of the stomach (n = 4), pancreas (n = 2), or colorectum (n = 6); all 2‑armed trials compared oral or enteral nutritional supplements with a standard diet pre- or perioperatively (n = 11) or before systemic anticancer treatment (n = 1). The studies reported findings on 15 different parameters in 7 categories and 6 of 11 trials reported significant findings (improvements in LOS, 2/9; complication rates, 2/10; body weight, 2/3 studies). However, omitting the nonrandomized studies, most trials were compromised because of a lack of blinding (all trials), overall high risk of bias (5 of the 6 trials reporting significant findings), and / or a lack of statistical correction for multiple testing (3 of 6 trials reporting significant findings). These factors make it difficult to extract new information in addition to what is known today.

In their Abstract, stating that dietary prehabilitation appears to convey a benefit, the authors are more optimistic than I would dare to be, given the collected data. But at the end of their article, they are more cautious and they wisely accept that definitive conclusions are not possible. And in this we agree with the assessments of the authors of the recent meta‑analyses. As long as professional prehabilitation is not routinely reimbursed, home‑based prehabilitation with guidance on nutrition and exercise may be offered widely. However, to gather more reliable evidence on the effects of prehabilitation, appropriately powered multicenter trials with a low risk of bias are required.⁸