Introduction
Prostate cancer is the most common cancer in UK men with almost 47,000 men diagnosed every year [
1]. Higher prevalence is associated with older age and 54% of all new cases are in men aged 70 and over [
1]. Poorer survival is also associated with older age, in particular for people over 70 [
2]. The reasons for this include multi-morbidity, which can make older men less able to tolerate treatment and its adverse effects resulting in worse adherence and non-completion [
1,
2]. Furthermore, poor levels of fitness may impact negatively on clinician and patient decision-making and consequently reduce access to curative cancer treatment [
3,
4]. With the advent of early chemotherapy for advanced disease and more complex adjuvant therapies, assessment of fitness prior to prostate cancer treatment is needed to optimise clinical outcomes in older men.
Cardiopulmonary fitness has traditionally been assessed before radical prostatectomy, as part of enhanced recovery pathways [
5] or prior to prehabilitation [
6]. It is well recognised that surgery can have a significant impact on catabolism and oxygen demand, and the length and extent of surgery is directly related to the risk of developing post-surgery complications [
7]. Eligibility for radical prostatectomy is often based on chronological age, but evidence shows that post-surgery complications are affected more by comorbidities than age [
8]. In clinical trials, even if there is no age limit, people are required to be “fit for treatment” as drug tolerance may decrease and toxicity may increase in those with poor fitness [
9]. For example, in the STAMPEDE prostate cancer trial, only men without a history of significant cardiovascular disease were recruited, reducing the number of older men in the study [
10]. Comorbidities can therefore be a significant barrier to clinical trial entry [
3].
Assessing patients in order to decide on the most appropriate treatment can be complex. Integrating functional and specialist assessments has been proposed as part of the international guidance for managing prostate cancer [
11]. The health status of older people with cancer can be very diverse. This means that they need a tailored approach to treatment that considers their cardiopulmonary fitness as well as their functional performance status [
12]. Cardiopulmonary fitness is associated with cardiovascular risk [
13,
14], and like physical strength, can be improved by physical activity [
15,
16].
People with cancer in comparison to age-matched people without cancer, have lower levels of cardiopulmonary fitness [
17‐
19]. This can be attributed, in part, to treatment morbidity, but may also be linked to a sedentary lifestyle, which has been found to increase the risks of some cancers, including prostate cancer [
20‐
23]. Exercise has been shown to alleviate Androgen Deprivation Therapy (ADT) related symptoms [
24] and increase survival in prostate cancer [
25,
26]. However, the design and delivery of appropriate lifestyle interventions requires a safe and simple assessment of fitness, to provide a personalised exercise prescription as a part of prehabilitation and rehabilitation programmes. Furthermore, it can provide an important pre-treatment benchmark to motivate patients to improve or sustain their physical activity levels. The development of a cheap and easy to implement assessment that provides a valid and reliable measure of fitness remains a challenge.
The cardiopulmonary exercise test (CPET) provides a direct measurement of aerobic capacity and peak oxygen consumption (VO
2peak) and is a gold standard in preoperative cardiopulmonary fitness assessment [
27,
28]. In prostate cancer, CPET is used for physical assessment and to evaluate preoperative risks [
29], alongside the American Society of Anesthesiologists Physical Status Classification System [
30,
31]. However, wider implementation of CPET in routine clinical practice is limited due to unavailability or high costs. The Siconolfi step test (SST) is simpler (it can be performed in any clinical or non-clinical setting) and cheaper than CPET. It has been validated to predict VO
2peak in healthy adults [
32,
33]. It has also been evaluated as a cardiopulmonary fitness assessment in patients with systemic lupus erythematosus [
34] and rheumatoid arthritis [
35]. To our knowledge, there is no study to evaluate the validity and reliability of SST in men with prostate cancer. SST is performed at a submaximal intensity of exercise, making it safe and suitable for elderly and frail men or people with disability. In this study, we evaluated SST against CPET and reported on the validity and reliability of SST in predicting cardiopulmonary fitness in men with prostate cancer. The reliability refers to the stability of SST in predicting cardiopulmonary fitness across time.
Discussion
The purpose of this study was to propose a valid and reliable methodology for a rapid fitness evaluation that requires minimal space and was easy to implement. Step tests have traditionally been used as an alternative to CPET for assessing cardiopulmonary fitness (e.g. Chester Step Test) [
46‐
49]. SST was selected because it has previously been validated to predict VO
2peak in healthy adults [
32,
33] and in other clinical populations [
34,
35]. The benefits of SST over CPET include simpler and cheaper implementation as well as equipment that is easily obtainable and transportable. An important advantage of SST is also that it fits within limited space e.g. a small clinical room and it can be delivered by non-clinical staff with minimal training. In this context, SST can also be safer than CPET because it is performed at a submaximal intensity of exercise.
Notably SST is one of many tests developed for a safe and pragmatic assessment of cardiopulmonary fitness. Other submaximal testing procedures that can be used for indirect estimation of VO
2peak include modified exercise ergometry protocols without spirometry, such as the Astrand-Ryhming nomogram to predict cardiopulmonary fitness [
43]. However, the main limitation of these assessments is that they require an expensive research-grade cycle ergometer. Treadmill protocols also exist, as well as walking or running tests [
50,
51], but they are not pragmatic in the context of non-laboratory, minimal space settings.
This study identifies the important issue of the need for evaluation of cardiopulmonary fitness of men with prostate cancer. The assessment is not only important in risk stratification of men prior to treatment. It also can be used to guide personalised exercise recommendations to optimise prehabilitation and rehabilitation interventions. The benefits of exercise on health-related quality of life are well evidenced in systematic reviews of randomized controlled trials [
52,
53]. Improving fitness has been shown to improve health outcomes and reduce cancer-related symptoms [
54,
55]. Furthermore, increased physical activity is associated with reduced risk of recurrence and improved survival [
26].
The aim of this study was to provide a scalable solution to these problems by improving men’s engagement in physical activity and their fitness. A growing body of evidence in support of the benefits of physical activity has led to the publication of exercise guidelines for cancer survivors [
56,
57]. Despite this, it is estimated that only 10–32% of cancer survivors meet the recommended physical activity levels [
58]. Therefore, an important first step in promoting physical activity, is to define individual fitness levels. The results of this study show that SST can provide a pragmatic and scalable alternative to CPET for the assessment of cardiopulmonary fitness in men with prostate cancer. It can be used to help tailor physical activity interventions to the needs and priorities of individual patients.
Barriers to the routine implementation of a fitness assessment in men with prostate cancer include resource constraints, time pressures to begin treatment and limited evidence regarding the benefits of testing men prior to treatment. CPET is expensive as it requires highly trained staff, specialist facilities and equipment such as a stationary exercise bike or a treadmill as well as ECG and oxygen uptake monitoring systems. While the British Thoracic Society 2017/2018 guidance [
56] states that CPET in outpatient or day-case settings in the UK costs £244, this does not cover the capital expenditure to purchase CPET equipment. In comparison, SST requires significantly less resources, no specialist equipment and less space. The equipment (a 10 in. (25.4 cm) step and a heart rate monitor) is cheap (total capital expenditure is approximately £162), small and portable.
CPET is a well validated benchmark measure of cardiopulmonary fitness, and it was used here to validate SST. This is an important strength of this study. In addition, both CPET and SST were performed twice in the same population, with the repeated measures allowing the reliability of SST to be assessed. Another strength of this study is the relatively large sample size, and a wide age range of participants (47–83) that is representative of the UK prostate cancer population. The reliability analysis cohort was 15% smaller than that which was available for the validity analysis. This was due to study attrition and missing data which are the main limitations of this study. In addition, VO
2peak (not VO
2max) was measured at the point of volitional termination. This is a more common measure in clinical populations of patients who are not trained athletes and unaccustomed to maximal intensity exercise. However, VO
2peak is a validated measure of cardiopulmonary fitness and similarly to VO
2max it represents cardiac output, vascularisation and oxygen utilisation by muscles [
41,
42].
Conclusions
This study highlights the importance of conducting validity and reliability work for SST as a predictor of VO2peak in men with prostate cancer. Age had a clear effect on the validity of SST for predicting cardiopulmonary fitness. For men aged 60 years and younger, SST predicted VO2peak values that were significantly lower than those measured with CPET. Caution is therefore advised when using SST to predict VO2peak in patients ≤ 60 years old, and further work is needed to establish the effect of age and HR on the validity of SST. Nevertheless, SST was a stable and reliable measure of fitness over time. In conclusion, these data present new evidence to support SST as a valid and reliable method for clinicians and rehabilitation specialists to assess and monitor cardiopulmonary fitness in men with prostate cancer. This assessment could be used to guide personalised exercise advice in pre- and post-treatment rehabilitation interventions. It could also be used in treatment decision making as it may help predict short and long-term outcomes of treatment. SST can be used in a wide range of clinical and non-clinical settings, and therefore could provide an alternative to the more expensive and resource demanding CPET.
Acknowledgements
We acknowledge funding to support this study from the Movember Foundation and Prostate Cancer UK grant number 250-20. We thank men and their families for their participation and contribution to the project. We thank clinicians from the Royal Surrey County Hospital NHS Foundation Trust and Newcastle upon Tyne Hospitals NHS Foundation Trust. We thank all members of the Study Advisory Committee for their contribution and their advisory role on the project, in particular John Heyworth and John Marshall, Patient and Public Involvement (PPI), Prostate Cancer UK. Fiona Archer is thanked for leading data collection and data entry aspects.