Discussion
To our knowledge, the FORCE trial is the first to study the effects of a structured pelvic floor rehabilitation (PFR) program after sphincter-saving rectal cancer surgery in a prospective randomized controlled trial with a well-defined rehabilitation program that uses all four important parts of pelvic floor training (pelvic floor muscle training, biofeedback, electrostimulation, and rectal balloon training) and includes an evaluation of quality of life and cost-effectiveness.
Previous studies that evaluated PFR after low anterior resection differed in terms of patient selection criteria and study design but differed most of all in the PFR protocols and fecal incontinence scoring systems [
11‐
15] used. Visser et al. (2014) noted the importance of consistent quality of life assessment in future trials with PFR since only one study had assessed this outcome before [
33]. This study protocol meets this need and will add a cost-effectiveness analysis for full implementation of the PFR.
The authors choose to publish this study protocol to prevent wasteful duplication of research effort and expenses but most of all to provide an insight into the decisions that were made during designing the FORCE trial. Several points will be discussed below.
Choices of questionnaires
The outcomes of this study will be assessed by standardized questionnaires. To date no consensus exists on how to evaluate the severity of fecal incontinence and its consequences for the Quality of Life [
21,
22,
34,
35]. A combination of the Wexner score and FIQL score is considered to give the most objective outcomes [
21], which is why these were incorporated into the study design. The DeFeC is used since this questionnaire incorporates various Rome IV criteria and scoring tools for constipation and fecal incontinence but also has reference population data available, which is important for the interpretation of results [
20]. For a better insight into the quality of life after LAR, the EORTC QLQ-CR29 was chosen. This list was preferred over several other questionnaires (i.e., the RAND36 or WHOQoL) since this one is a colorectal-specific module while the others asses the QoL from a general point of view. The presence of comorbidity, unrelated to defecation problems, in this aging group of patients might otherwise interfere with the reported quality of life.
The choices for the other questionnaires do not require additional explanation in our opinion.
Inclusion of patients regardless of the degree of their complaints
Where several previous studies selected patients with a specific amount of complaints/incontinence, we choose to include all patients without a predefined selection on the degree of postoperative complaints. This decision was based on the high percentage of patients that experience different types of functional bowel complaints after LAR and the hypothesis that all patients receiving the operation possibly could benefit from PFR. In addition, no uniformity exists in the cut-off value for our chosen primary endpoint, namely the Wexner incontinence score. The additional advantage of including unselected patients is that it allows a valid and more extensive statement to be made about a broad spectrum of patient’s characteristics, including their continence status, which are important in predicting a specific outcome after PFR.
Postoperative inclusion
The FORCE trial protocol was initially based on preoperative inclusion and included a preoperative measurement. Unfortunately, patients experienced an overload of preoperative information, and they stated that they wished to focus on their planned surgery. Therefore, we encountered serious difficulties in enrolling patients in the study, which is why we chose postoperative inclusion only. We are aware that this decision might introduce a selection bias, since patients already know the severity of their complaints. To report which specific type of patients refuse to participate, we started to ask patients who had denied full study participation to only fill in a single questionnaire regarding functional bowel complaints. We are also aware of the difficulties in reporting valid statements on the patient’s continence level before surgery. Determining the impact of surgery and/or radiotherapy in consideration of the preoperative continence level of the patient would be interesting, but this turned out to be infeasible. Since patients with serious postoperative complications (i.e., anastomotic leakage) are in a poor condition after surgery, this might induce selection bias as well. Therefore, this study likely cannot provide hard conclusions on FI and PFR after such serious problems.
Extensive anorectal manometric and function testing
Having patients fully examined with regard to manometry and anorectal functioning and objectively measuring what the effects of PFR are after rectal surgery [
36] would have been interesting. Especially since rectal (cancer) surgery with the construction of a low anastomosis might interfere with the puborectal continence reflex [
37,
38] and could induce clinical symptoms of fecal incontinence. However, such an examination turned out to be logistically infeasible for all patients due to the geographical spread of hospitals throughout the country and limited accessibility of anorectal function centers. In addition, the anorectal function devices that are currently used show a lot of variation regarding quality of measurements, which would make it difficult to make valid comparisons.
As with many randomized controlled trials, the FORCE trial is designed to make a difference in clinical daily practice. We believe that the results of this study can substantially improve care for patients with bowel dysfunction after LAR for rectal cancer. Subsequently, positive study results may be used in future guidelines, clinical practice algorithms, and eventually in the decision-making process of health insurances to reimburse PFR after LAR as standard care.
In case this study does not shows the hypothesized results, or in an insufficient amount, our considerations are in line with the statements of Bols et al. [
8] that the received physiotherapeutic interventions can still be of value. The patients’ awareness and capability to coordinate their pelvic floor system have increased, which are positive and expected to be useful in the future for this aging population.
Acknowledgements
The authors acknowledge the surgery departments; research assistants; and the participating physicians, nurses and pelvic floor physiotherapists of the participating hospitals and Pelvic Floor Physiotherapy centers for carrying out this study and comprising the FORCE Trial Group.
The FORCE trial group consists of all principal investigators, including surgeons, research coordinators, research/oncology/gastroenterology nurses, colorectal case managers, and participating pelvic floor physiotherapists. The following list of persons are included in the Force Trial Group:
Surgical staff and research staff: BR Klarenbeek, MWJ Stommel, JHW de Wilt, AJA Bremers, C Rosman, PR de Reuver, SAW Bouwense, BM van der Kolk, LM Garms, K Meerten-van den Belt, MRM Olde Hartman-Hofsté, JWM Peters, L Olsder, I Huizing, PMA Broens, M Trzpis, EJB Furnée, K Havenga, PHJ Hemmer, B van Etten, A Koop, L van der Heide, D Kamphuis, SA Koopal, C Hoff, H Eker, JPEN Pierie, HHM Junte, IJH Schoenaker, HL van Westreenen, S Quaedackers, MJ Bos, H Gardien, TC van Sprundel, PD de Vries, JF Ashruf, L Geurts, I Nielen, J Pfeil, M van Ark, SW Polle, B Hansson, F Polat, H de Vries, E ten Berge-Groen, AK Talsma, R Bosker, E Veurink, M Papa, AJG Maaskant-Braat, FJC van den Broek, WKG Leclercq, GD Slooter, F Caers, M Boeijen, R van den Broek, K van Schaik, DK Wasowicz-Kemps, BS Langenhoff, MJ van den Bogaard, J van der Sluis, D Arisz, S Bruinsma, DA Hess, EJ Mulder, B Wiering, S Kok, J Woltering, B Raap-van Sleuwen, L Schoonderwoerd, D Hendriks, N van den Elzen, I van de Laak, M Valk, W van der Meij, BJ van Wely, MJ van Hoogstraten, M van der Sluis, I Paulusma, MJW Möllers, R Looijen, HCJ van der Mijle, ITA Pereboom, PMC Tijink-Callenbach, RA Schasfoort, W van de Meer, M Lubberink, M van Haskera, F Wit, M Jeeninga, R ten Hoeve, FCW Slootmans, B Inberg, L de Nes, Dianne Toonen, MA Wilmsen, O Buyne, and F Ferenschild.
Pelvic Floor Fysiotherapists: C Adamse, BL Hettema-Beets, MK Goudswaard, M van der Velde, DW Elving, RE Arends-Smit, JR Buiter, I van der Witte-van Aerle, K Jansma, L Kooistra, S Lohof-Venema, MR Kruijer, G Dijkstra, MA van der Werf-Elling, V Kats-de Boer, A M Rinsema, M Haarlemmer – Lutjeboer, A Van der Vegt, SMH Berends-Pors, AJ Ponstein, G Klaassen, AM Nieuwint, M Veninga-Jansen, V Dries-Jansen, FJ Arends, NE Stellingwerf-Goinga, NWG Overmars, H Van Asma, K Beverdam, MJAC Ploumen, M Tijhuis, AH Visser Duiven, M Former, MAL Smans-Kaal, CMJ Vorsterman van Oijen-Linthorst, N.N. Hövels-Kamp, LR Vorsteveld, N Vermeulen, A Alkemade- van Veghel, LJW Steentjes, HGM Cornelisse-Theunissen, J Strijbosch, S Sniekers, JMA Oerlemans-van Oijen, HMJ Hoefnagels, CJDA Sniekers, S Biemans, Y Bomert-Wendt, HGM van Gaal, AHCW Smulders, W Adams, JM Kappen, AM Vermeltfoort-Jansen, MGC Zegger, C Vrielink, HM Slotman, NJH Claessens, AWM Manders-de Groot, CTPG van Beuzekom- van der Vorst, MWC Swinkels- Nijssen, P van Oeveren, JPF van Leeuwen-Nellestijn, M Bleijenberg, JJF Valenteyn-Hidden, MG van Rutten-de Groot, M van den Nieuwenhuizen, PG Boorsma, N Broodman, ME Elling, E Bokkers-Engelen, GH Hilhorst-Droppers, and Mein, HJC.