Results from this study found that the 6MWT appears to be highly repeatable in oncological patients scheduled for major surgery. Nonetheless, the high proportion of patients increasing the distance covered during the second 6MWT shows that a learning effect in this population, as observed previously in other clinical settings . Unfortunately, no determinator of improvement was found among the variables studied. These findings suggest that performing at least two attempts is recommended in preoperative cancer patients to accurately determine patients’ functional capacity.
Over the last years, increasing evidence has been generated on the potential of prehabilitation to optimize physical and psychological resilience to cope with stress generated by major oncological surgical procedures  and 6MWT distance is usually considered an outcome of prehabilitation programs . Guidelines to perform the 6MWT were first published by the American Thoracic Society (ATS) over 20 years ago  and initially stated that a practice test was not necessary for most clinical scenarios as the mean change from the first to the second was considered to be low. However, several authors have since then recommended using a familiarization trial to establish a baseline 6MWT [9, 29, 30] while some other studies have neglected the need for a second test [31, 32]. In patients which chronic respiratory diseases as well as cardiac failure, studies have shown that there is a significant difference in the distance covered between the first and the second test, with improvements ranging from 24 to 29 meters . Indeed, a systematic review and meta-analysis conducted in 2014 in COPD, found a pooled mean increase of 26.1m in the second test . Furthermore, this learning effect seems to exist not only when the tests are performed on the same day but also when performed separated by several weeks or months [30, 33]. In cancer patients, the study conducted by Schmidt et al. , also showed a mean increase in the second test of 16.6±29.9 m (95% CI: 5.5 - 27.8) with 80% of the patients walking farther than on the first attempt, which is consistent with our results. Our findings conducted in a more heterogenous sample of recently diagnosed cancer patients, confirmed that there is indeed a learning effect in this population (mean difference 19.5, 95% CI: 15.6 – 23.5) with 80% of patients walking more during the second test. The Bland-Altman plot further confirmed this difference with limits of agreement ranging from -31.3 to 70.4m, well over the MCID reported for several clinical populations . As performing a second 6MWT is time-consuming (an additional 40 minutes including resting from the first test and performing the second) and sometimes it is not well accepted by the patient (severe deconditioning, musculoskeletal impairments, etc.), it would be of great interest to identify potential factors associated with presumably improving the distance walked during the second test. This would allow us to select those patients in which a second test might be necessary for reliable results. Unfortunately, we were not able to identify any determinator of significant improvement among the clinical and anthropometric variables assessed in this study. In addition, no differences in the magnitude of learning effect were found between men and women neither between older and younger patients, which suggest that the variability is due to within subject factors (motivation, readiness, fatigue, etc.). As so, two attempts of the test should be encouraged in this population to accurately assess functional capacity. Nevertheless, in some scenarios, the clinical decision of performing a practice test or not could depend on the purpose of the assessment  and well as the baseline level of functional capacity (i.e: patients walking ≥ 500 meters might not need a second test if the purpose is assessing the surgical risk as they would be already considered low-risk). Undoubtedly, more studies are warrant in this line to determine whether one test could be enough in these cases.
Despite the existence of a learning effect reported in many clinical populations, the 6MWT has shown an excellent test-retest reliability and reproducibility across different populations including chronic cardiovascular and respiratory diseases [15, 31, 35], neurological conditions[36, 37] as well as healthy subjects . However, when comparing studies, we observe that terminology used in these studies (reproducibility, replicability and reliability) is sometimes used interchangeably when they actually refer to different test properties, which hinders the interpretation and comparison of the results across studies. While reproducibility requires measurements to be undertaken under different conditions (i.e: different assessors or different populations), repeatability is measured under identical circumstances over a short period of time . Both constructs are usually assessed with the ICC to quantify reliability between the measurements and/or determination of agreement with a Bland-Altman plot . In our study, as in previous studies with smaller samples in cancer patients [7, 39], we found an ICC of 0.98 between two 6MWT conducted under identical conditions, showing excellent repeatability. In addition, the coefficient of variation was very low and similar to other previous studies [5, 14]. Furthermore, no proportional bias was found showing that limits of agreement do not change significantly with different mean values of the test. So, although this is not the first study to evaluate the reliability and repeatability of the test in a cancer population, it is definitely the one with the highest and heterogeneous sample. In addition, the quality of our data was reinforced by the replicability of the physiological responses observed in both tests (ICC ranging from 0.6 to 0.83).
This study has some limitations that we must address. To start with, this is a sub-analysis derived from a large longitudinal study whose main objective was to analyze the feasibility and effectiveness of a multimodal prehabilitation program in a real-world scenario. Therefore, the sample size used might not be adequate for some of the analysis performed (i.e: identify potential factors associated with a meaningful change in the second 6MWT), although similar studies have been conducted where sample sizes are considerable smaller than ours [14, 39]. In addition, a selection bias might have occurred as some of the patients were excluded from the final sample due to missing data on the 6MWT or refusal to perform a second test. However, in this case, after conducting an exploratory analysis between excluded and included patients, no relevant differences in clinical characteristics were found besides the excluded patients being more likely men (p<.05).
In summary, this study provides new evidence that the 6MWT is a highly replicable test with consistent agreement to assess functional capacity in preoperative cancer patients who are scheduled for major surgery, but with a significant learning effect. Therefore, our findings support the recommendation of a practice 6MWT at baseline assessment for most clinical scenarios. Future studies are needed to determine whether one test could be enough in some selected cases (for instance, highly functional patients).