Changes in health-related outcomes among colorectal cancer patients undergoing inpatient rehabilitation therapy: a systematic review of observational and interventional studies

Figures & data

Table 1. Characteristics of included observational studies, relevant findings among CRC rehabilitants, and results of the quality assessment.

							Re-assessment^b		Relevant findings /quality assessment (total score)
First author Year Country	Study design Comparison group never included	Inclusion criteria	Included CRC patients^a	Therapy / duration (days)	Relevant outcomes	Instruments used	Short-term	Long-term
Mix 2017 USA [35]	Retrospective patient cohort	Cancer diagnosis Age ≥18 years First rehabilitation program Survived through to discharge Discharged between Oct 2010 and Sept 2012	1732	Routine inpatient rehab. therapy ∼11.3^c	Functional status	FIM (Functional Independence Measure)	✓		Functional gain was observed at discharge. Patients with digestive cancers had the largest functional gain. TS 3≙ moderate limitations
Biskup 1994 Germany [36]	Prospective patient cohort	Breast, CRC All stages All ages First rehab. program	40	Routine inpatient rehab. therapy 28	Physical status	Beschwerdenliste B-L (Zerssen’s list of somatic complaints)	✓	✓	Significant improvement in physical status during rehabilitation. Increase of impairments beyond the initial level 6 months after rehabilitation. TS 2≙ strong limitations
	b. Prospective patient cohort	Breast, CRC All stages All ages	83	Routine inpatient rehab. therapy^d	Physical status	Beschwerdenliste B-L (Zerssen’s list of somatic complaints)	✓	✓	No improvements in physical status during or 3 and 6 months after rehabilitation. TS 3≙ moderate limitations
Allgayer 2012 Germany [38]	Prospective patient cohort^e	Cancer and non-cancer patients after ano-rectal surgery Stage I–III Age ≤70 years No tumor recurrence Fecal incontinence Karnofsky index ≥ 80 No severe comorbidities	67^f (rectal cancer)	Routine inpatient rehab. therapy including intensive pelvic floor exercise with/without biofeedback 21–28	Fecal Incontinence	MCIS (Modified Cleveland Incontinence Score)	✓	✓	No difference in levels of fecal incontinence between non- and irradiated-rehabilitants at admission. Significant reduction in levels of fecal incontinence in both groups during rehabilitation. Deteriorations 1 year after rehabilitation up to initial values. TS 4≙ moderate limitations
Allgayer 2005 Germany [37]	Prospective patient cohort	CRC Stage I–III Age ≤ 75 years Fecal incontinence Karnofsky index ≥ 80 No severe comorbidities	95	Routine inpatient rehab. therapy including intensive pelvic floor exercise with biofeedback 21	Fecal Incontinence	MCIS (Modified Cleveland Incontinence Score)	✓	✓	Irradiation was significantly associated with higher levels of fecal incontinence at the start of rehabilitation. Significant reduction in levels of fecal incontinence during and 1 year after rehabilitation compared to admission in both groups.
									Slight increase in levels of fecal incontinence 1 year after rehabilitation.
									Treatment failure during and 1 year after rehabilitation: in 9 (9/95) and 19 (19/71)
					Anal pressure sensation/pain spincter length	Rectal manometry Ballon instillation Rectal endoscopy	✓	(✓)^g	No significant change in anal pressure or sensation / pain during rehabilitation. TS 4≙ moderate limitations
Klocker 2018 Austria [40]	Prospective patient cohort	Cancer diagnosis Returned questionnaire at discharge	291	Routine inpatient rehab. therapy 21	QOL (health status)	EuroQoL-EQ-5D-VAS (EuroQoL five-dimensional Questionnaire)	✓	(✓)^h	QOL improved during rehabilitation.
					Anxiety and depressive symptoms	HADS (Hospital Anxiety and Depression Scale)	✓	(✓)^h	Levels of anxiety and depression decreased during rehabilitation. TS 2≙ strong limitations
Lamprecht 2017 Germany [39]	Prospective patient cohort	Breast, prostate, colon cancer Stage I–III Age 18–75 years No tumor recurrence First rehabilitation program	37	Routine inpatient rehab. therapy^d	QOL	EORTC-QLQ-C30^i (EORTC Core Quality of Life Questionnaire)	✓	✓	QOL improved during rehabilitation (except financial problems) with greatest and significant improvement in global QOL and fatigue. Smaller improvements or deteriorations were reported 3 months after rehabilitation. Largest and significant improvements in physical functioning.
					Anxiety and depressive symptoms	HADS (Hospital Anxiety and Depression Scale)	✓	✓	No significant change in number of positive screened individuals for anxiety and depression in the course of time TS 4≙ moderate limitations
Singer 2009 Germany [31]	Prospective patient cohort	Cancer diagnosis Age >69 years Completed or immediately preceding anti-tumor therapy	54^f	Routine inpatient rehab. therapy 21	QOL	EORTC-QLQ-C30^i (EORTC Core Quality of Life Questionnaire)		✓	Clinically relevant and positive change in global QOL and in the following functional scales 4 months after rehabilitation: physical, emotional, role and social as well as in the symptom scales: fatigue, dyspnea, nausea and vomiting, pain, appetite loss. No or no clinically relevant change in the scales: cognitive functioning, financial problems, sleep, diarrhea and constipation TS 4≙ moderate limitations

CRC: colorectal cancer; QOL: Quality of Life, TS: Total Score.

^aNumber of rehabilitants with CRC that were included in the analyses (first re-assessment);

^bShort-term is defined as at the end of treatment or at discharge; Long-term is defined as 3 to 12 months after inpatient rehabilitation therapy;

^cMean duration of treatment was 11.3 days in the group of patients with digestive cancer sites;

^dInformation about duration is not provided. Standard therapy in Germany lasts for about 21–28 days;

^eOriginally reported as prospective, comparative study (evaluating the predictive value of medical findings by endorectal ultrasound and real-time elastography on fecal continence);

^fNumber of CRC patients at baseline. Results are not stratified by entity or disease but ≥70% of study population or relevant subgroup are patients with CRC;

^g22 patients were reexamined during a second rehabilitation clinic stay;

^hOnly a subset of participants was followed-up 6 and 12 months after rehabilitation therapy. Relevant information was not reported separately for cancer entities;

ⁱQuality of life core questionnaire by the European Organisation for Research and Treatment of Cancer.

Table 2. Characteristics of included interventional studies, relevant findings among CRC patients and results of the quality assessment.

							Re-assessment^b		Relevant findings/quality assessment (total score)
First author Year Country	Study design	Inclusion criteria	Included CRC patients^a	Intervention duration (days)	Relevant outcomes	Instruments used	Short-term	Long-term
Ross 2015 Denmark [43]	RCT	Breast, prostate, CRC Low and high risk cancer Time since diagnosis ≤2 years Completed primary treatment Life expectancy ≥5 months	124^c Intervention arm: 54 Controls: 70	Multi-focus psychosocial empowerment intervention Controls: usual clinical care 6	Distress	TMD (Total mood Disturbance score derived from the Profile of mood short Form)	(✓)^d	✓	No association between changes in distress and group assignment, even when stratified by age, education and cancer site. TS 5≙ minor limitations
Allgayer 2008 Germany [42]	RT^e	CRC Stage I to III Age ≤75 years Completed anti-tumor therapy Karnofsky index ≥80 No severe comorbidities	44 Higher exercise intensity: 27 Lower exercise Intensity: 17	Routine care + aerobic exercise (50–60% vs. 30–40% × max. exercise capacity)^f 14	DNA-damage (Urinary 8-oxo-dG^g)	Mass spectrometry	✓		Significant decrease in 8-oxo-dG execration levels in the lower exercise intensity group. Non-significant increase in the higher exercise intensity group. TS 2≙ strong limitations
Allgayer 2004 Germany [41]	RT	CRC Stage II or III Age ≤65 years Completed anti-tumor therapy Karnofsky index ≥85 No severe comorbidities	23 Higher exercise intensity: 13 Lower exercise Intensity: 10	Routine care + aerobic exercise (55–65% vs. 30–40% × max. exercise capacity)^f 14	Inflammatory cytokines and antagonist response	Blood samples under LPS-stimulation^h	✓		LPS-stimulated interleukin-1 receptor antagonist decreased (IL-1 ra) significantly with higher exercise intensity. Possible link to pro-inflammatory response and decreased susceptibility to infection. TS 2≙ strong limitations

CRC: colorectal cancer; RCT: randomized controlled trial; RT: randomized trial (randomization to different exercise intensity groups, no quantitative comparison between groups, only within groups).

^aNumber of rehabilitants with CRC that were included in the analyses (first re-assessment);

^bShort-term is defined as at the end of treatment or at discharge; Long-term is defined as 12 months after inpatient rehabilitation therapy;

^cResults are not provided by cancer site but statistical testing showed no interaction between treatment effect and cancer site;

^dShort-term assessment after treatment and further re-assessments have been published elsewhere [44,45] but relevant information about entity-specific outcomes is not provided for participants with CRC;

^eSwitching to the alternate exercise group was allowed after randomization;

^fType of exercise was not reported but stationary bike was used for max. exercise capacity test;

^g8-Oxo-2′-deoxyguanosine;

^hLPS Lipopolysaccharide.

Figure 1. PRISMA flow diagram of literature search and study selection process. *The article by Biskup et al. [36] covers two individual studies.

Mix JM, Granger CV, LaMonte MJ, et al. Characterization of cancer patients in inpatient rehabilitation facilities: a retrospective cohort study. Arch Phys Med Rehabil. 2017;98(5):971–980.

 PubMed Web of Science ®Google Scholar

Biskup M, Uhlemann T, Gärtner U. Veränderungen körperlicher Beschwerden und Belastungen von Tumorpatienten nach stationärer onkologischer Rehabilitation [Changes in physical complaints and stress in tumour patients after inpatient oncological rehabilitation]. Prax Klin Verhaltensmed Rehabil. 1994;28:219–229. German.

 Google Scholar

Allgayer H, Ignee A, Zipse S, et al. Endorectal ultrasound and real-time elastography in patients with fecal incontinence following anorectal surgery: a prospective comparison evaluating short- and long-term outcomes in irradiated and non-irradiated patients. Z Gastroenterol. 2012;50(12):1281–1286.

 PubMed Web of Science ®Google Scholar

Allgayer H, Dietrich CF, Rohde W, et al. Prospective comparison of short-and long-term effects of pelvic floor exercise/biofeedback training in patients with fecal incontinence after surgery plus irradiation versus surgery alone for colorectal cancer: clinical, functional and endoscopic/endosonographic findings. Scand J Gastroenterol. 2005;40(10):1168–1175.

 PubMed Web of Science ®Google Scholar

Klocker J, Klocker-Kaiser U, Pipam W, et al. Langzeitverbesserung der biopsychosozialen Situation onkologischer Patienten durch 3-wöchige stationäre onkologische Rehabilitation [Long-term improvement of the bio-psycho-social state of cancer patients after 3 weeks of inpatient oncological rehabilitation: a long-term study at the Humanomed Zentrum Althofen]. Wien Med Wochenschr. 2018;168(13–14):350–360. German.

 PubMed Web of Science ®Google Scholar

Lamprecht J, Thyrolf A, Mau W. Health-related quality of life in rehabilitants with different cancer entities. Eur J Cancer Care. 2017;26(5):e12554.

 Web of Science ®Google Scholar

Singer S, Schulte T. Lebensqualitat von alteren Tumorpatienten. Bedarf an und Nutzen von Anschlussheilbehandlungen [Quality of life in elderly cancer patients-need for and benefit of inpatient rehabilitation]. Dtsch Med Wochenschr. 2009;134(4):121–126. German.

 PubMed Web of Science ®Google Scholar

Ross L, Rottmann N, Andersen KK, et al. Distress after a psychosocial cancer rehabilitation course. Main effects and effect modification in a randomised trial at 12 months of follow-up. Acta Oncol. 2015;54(5):735–742.

 PubMed Web of Science ®Google Scholar

Allgayer H, Owen RW, Nair J, et al. Short-term moderate exercise programs reduce oxidative DNA damage as determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry in patients with colorectal carcinoma following primary treatment. Scand J Gastroenterol. 2008;43(8):971–978.

 PubMed Web of Science ®Google Scholar

Allgayer H, Nicolaus S, Schreiber S. Decreased interleukin-1 receptor antagonist response following moderate exercise in patients with colorectal carcinoma after primary treatment. Cancer Detect Prev. 2004;28(3):208–213.

 PubMedGoogle Scholar

Ibfelt E, Rottmann N, Kjaer T, et al. No change in health behavior, BMI or self-rated health after a psychosocial cancer rehabilitation: results of a randomized trial. Acta Oncol. 2011;50(2):289–298.

 PubMed Web of Science ®Google Scholar

Rottmann N, Dalton SO, Bidstrup PE, et al. No improvement in distress and quality of life following psychosocial cancer rehabilitation. A randomised trial. Psychooncology. 2012;21(5):505–514.

 PubMed Web of Science ®Google Scholar