Patients treated with chemoradiotherapy for non-metastatic anal squamous cell carcinoma may continue to experience considerable physical, functional, and social challenges long after treatment has ended, according to a study published in Radiotherapy and Oncology.
The cross-sectional cohort study found that patients reported lower overall health-related quality of life, reduced functioning across every assessed domain, and a greater burden of symptoms compared with people of a similar age, sex, and comorbidity profile without cancer.
The findings highlight a central challenge in anal cancer survivorship: successful cancer treatment does not always mark the end of treatment-related difficulties.
Title: “Patient-reported quality of life after chemoradiotherapy in patients with non-metastatic anal squamous cell carcinoma: A cross-sectional cohort study”
Authors:R. A. Lunenberg, F. N. van Erning, F. P. C. Sijtsma, I. H. J. T. de Hingh, B. van Triest, B. A. Grotenhuis, M. Koopman, M. P. W. Intven, J. M. L. Roodhart, J. J. M. Kwakman, PLCRC Study Group
Looking Beyond Disease Control
Chemoradiotherapy is the standard treatment for most patients with stage I–III anal squamous cell carcinoma. The approach can provide locoregional disease control while allowing many patients to avoid abdominoperineal resection and a permanent stoma.
However, information about the long-term effect of chemoradiotherapy on patients’ everyday lives remains limited.
The researchers noted that treatment may affect bowel, urinary, sexual, physical, emotional, and social functioning. These effects may persist after treatment, even when the cancer has been successfully controlled.
To better understand this burden, the investigators examined patient-reported outcomes from the Prospective Dutch ColoRectal Cancer cohort and linked them with clinical information from the Netherlands Cancer Registry.
Assessing Life After Treatment
The analysis included 72 adults diagnosed with stage I–III anal squamous cell carcinoma between 2016 and 2025.
All patients had completed at least one health-related quality-of-life questionnaire six months or more after finishing chemoradiotherapy. The median interval between the end of treatment and completion of the main quality-of-life questionnaires was 21.7 months.
The median age at diagnosis was 65 years, 67% of the participants were women, and nearly half had stage III disease.
Most patients received chemoradiotherapy with mitomycin and capecitabine, and 83% completed the planned chemotherapy regimen.
Patient-reported outcomes were assessed using several questionnaires covering general quality of life, physical and emotional functioning, colorectal symptoms, bowel dysfunction, and quality of life among people living with a stoma.
The results from the main quality-of-life questionnaire were compared with those of 216 individuals from the Dutch general population who were matched by age, sex, and comorbidity burden.
Lower Quality of Life Across Every Functional Domain
Patients treated for anal cancer reported a lower global health status than the matched population.
The mean global health score was 68.5 among patients compared with 78.5 among controls. The overall questionnaire summary score was also lower, at 79.3 compared with 91.1.
All assessed functioning domains were reduced by at least 10 points, indicating clinically relevant differences.
The largest gap was observed in social functioning. Patients had a mean social functioning score of 73.1, compared with 94.7 in the matched population, a difference of 21.6 points.
Physical, emotional, cognitive, role, and social functioning were all affected, showing that the consequences of treatment extended beyond individual symptoms and influenced multiple aspects of daily life.
Fatigue and Diarrhoea Remain Important Concerns
Patients reported a higher symptom burden across all assessed symptom categories compared with the normative population.
Fatigue and diarrhoea were the symptoms that exceeded the threshold for clinical relevance.
Additional commonly reported problems included urinary frequency, buttock pain, abdominal discomfort, bloating, flatulence, faecal incontinence, altered stool frequency, and embarrassment related to defecation patterns.
Urinary frequency had a mean symptom score of 33.1, while buttock pain had a mean score of 27.1. Flatulence was particularly prominent among patients without a stoma.
Patients also reported difficulties involving body image, anxiety, sexual interest, and sexual function. Among men who answered the relevant question, the mean score for erectile dysfunction was 56.4.
Although relatively few participants completed the sexual health items, the available responses suggested that sexual consequences remain an important component of survivorship care.
Major Bowel Dysfunction Reported by Most Patients Without a Stoma
Bowel dysfunction emerged as one of the study’s most significant findings.
Among patients without a stoma who completed the Low Anterior Resection Syndrome questionnaire, 62% reported symptoms consistent with major LARS, while a further 19% reported minor LARS.
The most frequently reported severe bowel symptoms included:
- Strong urgency to open the bowels
- Incontinence for gas
- Needing to open the bowels again within one hour
At baseline, before treatment, only 13% of the patients with available data reported major LARS, while 56% reported no LARS.
The comparison suggests that bowel-related symptoms may become substantially more pronounced following chemoradiotherapy.
Although the LARS questionnaire was originally developed for patients who had undergone rectal surgery, the researchers used it as a practical measure of bowel dysfunction after pelvic radiotherapy.
Living With a Stoma
Twenty-three patients completed questions related to stoma quality of life.
Their mean overall satisfaction-with-life score was 66.5. Five patients reported that they often or always worried about travelling because of their stoma.
Three patients said they were never or rarely able to carry out hobbies, while another three reported being unable or rarely able to complete the same household tasks they had managed before.
The study included only three patients who had undergone abdominoperineal resection, meaning the effect of this surgery on quality of life could not be determined separately.
Some Symptoms Improve, While Others Emerge
Baseline quality-of-life information was available for only a limited number of patients and should therefore be interpreted cautiously.
Nevertheless, the available comparisons suggested that some cancer-related symptoms improved after treatment, while several treatment-related effects became more prominent.
Blood or mucus in the stool, constipation, and bloating were worse before treatment than during follow-up.
In contrast, patients reported worsening urinary incontinence, dry mouth, changes in taste, hair loss, faecal incontinence, body image, and pain after treatment.
The researchers noted that these patterns may reflect the successful control of tumour-related symptoms alongside the development of persistent effects associated with chemoradiotherapy.
Survivors May Face More Than They Expected
Previous research has shown that clinicians may underestimate the severity of symptoms reported by patients after chemoradiotherapy for anal cancer.
The authors also highlighted evidence that some patients experience long-term adverse effects that are more severe than they expected before treatment.
This makes early and honest communication particularly important. Patients may benefit from receiving clear information not only about the likelihood of cancer control, but also about possible long-term changes in bowel function, urinary symptoms, sexual health, fatigue, pain, and social functioning.
Preparing patients for these possibilities may help manage expectations and encourage earlier reporting of symptoms.
A Need for Structured Supportive Care
The study supports a broader role for patient-reported outcome measures during routine follow-up.
Regular assessment could help healthcare professionals identify persistent symptoms that may not emerge during standard clinical discussions. It may also allow supportive care to be tailored to the needs of each patient.
Potential areas of support may include bowel and continence management, fatigue care, pain management, pelvic rehabilitation, sexual health services, stoma support, psychological care, and assistance with returning to work and social activities.
The authors emphasised that survivorship care should address not only disease recurrence but also the lasting consequences of treatment.
Can Treatment Become Less Burdensome?
Efforts are underway to reduce treatment-related side effects without compromising cancer control.
The PLATO-ACT4 phase 2 trial has investigated reduced-dose intensity-modulated radiotherapy with concurrent chemotherapy for patients with early-stage anal cancer. Early findings suggested lower rates of severe acute toxicity with the reduced-dose approach while maintaining comparable short-term oncological outcomes.
Other studies are evaluating proton radiotherapy and more personalised approaches to treatment planning.
At the same time, clinical trials are exploring the addition of immune checkpoint inhibitors to improve disease outcomes. The challenge will be to balance treatment intensification with the need to protect long-term quality of life.
Important Study Limitations
The authors acknowledged several limitations.
The study included patients who had enrolled in the PLCRC cohort and agreed to complete questionnaires, which may have introduced selection bias.
Baseline patient-reported outcome data were available for only a small proportion of participants, and the study could not examine how symptoms changed at standardised intervals over time.
The timing of questionnaire completion also varied between patients, although questionnaires completed within six months of treatment were excluded and the assessment closest to 24 months was selected whenever possible.
In addition, the study did not use an anal cancer-specific quality-of-life questionnaire. Future research is expected to incorporate the EORTC QLQ-ANL27, which was developed to assess bowel symptoms, stoma care, pain, urinary problems, sexual health, and other concerns specific to anal cancer.
Survivorship Must Extend Beyond Cure
The study demonstrates that patients with non-metastatic anal squamous cell carcinoma may experience reduced quality of life and substantial functional difficulties long after chemoradiotherapy.
Fatigue, diarrhoea, bowel dysfunction, urinary symptoms, pain, and limitations in social and role functioning remained prominent nearly two years after treatment for many participants.
The findings reinforce the need to make supportive care, patient education, and routine symptom assessment central components of anal cancer follow-up.
For survivors, the goal should extend beyond controlling the disease. It should also include helping patients recover function, manage persistent symptoms, and rebuild their quality of life after treatment.
Written by Nare Hovhannisyan, MD
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