Evolving Concepts in the Management of IBD in Patients with Cancer

March 18, 2025

Introduction

The objectives of this presentation were to create a framework for thinking about management of inflammatory bowel disease (IBD) in the setting of active and past cancer, review available data on cancer risk in IBD, the impact of cancer therapies on IBD, and the role of immunosuppressive therapies on cancer, and lastly, to translate these data into actionable items for clinical practice.

A Canadian population-based study published in 2001 found an increased risk of colon and hepatobiliary cancer in ulcerative colitis (UC) and Crohn’s disease (CD), an increased risk of rectal cancer specific to UC, and increased risk of lymphoma specific to males with CD.¹ More recent data from Canada have shown a decrease in the incidence of intestinal cancer (-1.2%), but an increased risk of extraintestinal digestive cancers such as liver or bile duct cancer (+3.3%).²

In practice, gastroenterologists often see patients who receive a cancer diagnosis or have a history of cancer. In these situations, first, it is important to recognize cancers related to active IBD (colorectal, small bowel, intestinal lymphoma, anal carcinoma, cholangiocarcinoma) and those related to IBD therapy (lymphoma, melanoma, non-melanoma skin cancer, genitourinary).³ When gastroenterologists are faced with a patient with IBD who has cancer, they should consider the nature of their cancer, the impact of IBD on their cancer, and the impact of cancer therapy on their IBD (Figure 1).

Impact of IBD Therapies on Cancer

While data on active cancer in IBD are limited, studies have examined de novo cancers associated with the use of immunosuppressive medication in IBD. These have consistently identified an increased risk of certain types of cancers with thiopurines (non-melanoma skin cancer [NMSC], lymphoma, urinary tract cancer), anti-TNFs (lymphoma, potentially melanoma), and their use in combination (lymphoma).^4-7 More limited data on newer agents including anti-interleukin (IL)-12/23, IL-23 inhibitors, and anti-integrins do not suggest an increased risk of malignancy.^8-10 Based on limited data, Janus Kinase (JAK) inhibitors include a warning of increased risk of lymphoma, lung cancer, and NMSC in their product monographs.^11,12

Impact of Cancer Therapy on IBD

When treating a patient with IBD and active cancer, it is also important to consider the potential impact of the cancer therapy on their IBD.

Checkpoint Inhibitors

Checkpoint inhibitors include cytotoxic T-lymphocyte associated protein 4 (CTL4A), programmed cell death (PD)-1, or partner protein programmed cell death ligand (PD-L)-1 agents, which are used to treat breast, bladder, cervical, colorectal, head and neck, Hodgkin lymphoma, liver, lung, renal cell, skin (melanoma), and stomach cancer. This class of agents is associated with gastrointestinal (GI) side effects such as hepatitis and colitis.¹³

In terms of their use in individuals with IBD, a meta-analysis on the safety and tolerability of checkpoint inhibitors in patients with pre-existing IBD (n=193) found that 40% had a relapse of their IBD, of which 76% required steroids, and 37% required biologics. Overall, 35% discontinued checkpoint inhibitors but GI complications (perforation or surgery) occurred in less than 5% of patients. Furthermore, CTLA-4 agents were associated with a higher risk of IBD relapse than PD-1 and PD-L1 inhibitors.¹⁴ The American Gastroenterological Association (AGA) Clinical Practice Update on the Management of Checkpoint Inhibitor Colitis and Hepatitis provided expert recommendations stating that patients with IBD may have increased risk of GI side effects with checkpoint inhibitors but may derive benefit for the treatment of their cancer. For those that develop colitis on checkpoint inhibitor therapy, the recommendations were that prednisone over 4–6 weeks is effective and that infliximab and vedolizumab are reasonable options for steroid refractory colitis. Furthermore, checkpoint inhibitors may be restarted if clinical remission of IBD is achieved.¹⁵

Chemotherapy

Interestingly, patients with IBD receiving chemotherapy often go into remission and several small studies support this clinical experience. For example, a US study in 84 patients with active IBD and extraintestinal cancer found that almost all treated with cytotoxic chemotherapy achieved remission of their IBD and remained in remission at 5 years.¹⁶ Similarly, a European study of 41 IBD patients who received chemotherapy found a significantly lower mean number of IBD exacerbations after chemotherapy than before, as well as a significant reduction in IBD therapy use after chemotherapy.¹⁷

Hormone Deprivation Therapy

Hormone deprivation therapy in prostate cancer reduces the production or action of testosterone and in breast cancer reduces estrogen levels and/or estrogen binding to tumour cells. A US retrospective study assessed the impact of hormone therapy for prostate or breast cancer and risk for relapse of IBD and found that hormone deprivation therapy was associated with an increased risk of IBD relapse.¹⁸

Radiation Therapy

Data on the safety or radiation therapy in patients with IBD are accumulating. A systematic review of patients with prostate cancer and IBD included 12 retrospective studies (n=194) and found the rate of acute and late Grade 2+ GI events to be 15.3% and 11.3%, respectively, while Grade 3+ GI acute and late events occurred in 3.4% and 2.3% of patients, respectively.¹⁹ Furthermore, a study in patients with IBD and concomitant prostate cancer treated with radiation therapy found increased rates of IBD flares at 6 months compared to those treated with non-radiation modalities (10.6% vs. 5.7%).²⁰ In addition, a multicentre cohort study from the Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) investigated the impact of abdominal or pelvic radiotherapy on IBD activity and found rates of survival without IBD flare at 1 and 3 years after radiotherapy of 82.5% and 70.6%, respectively. However, an area of specific risk is patients with ileal pouches, as pelvic radiation has been shown to be associated with a significantly higher rate of pouch failure and pouch-related symptoms. Thus, careful consideration is needed in this patient population.²¹

History of Cancer

For patients with IBD and a history of cancer, both the nature of their prior cancer and their current or proposed IBD therapy should be considered. Whether prior cancer was completely eradicated or is at risk of re-activation, the risks of cancer recurrence associated with IBD therapy must be balanced against the risk of IBD flares and complications. Trials of IBD therapies generally exclude patients with active cancer or cancer within the previous 5 years, therefore data remain limited. However, the greatest risk factor for incident cancer is the stage and type of previous cancer.

An analysis of the CESAME prospective cohort (n=17047) found an increased risk of new cancer after a first cancer, with no increased risk associated with immunosuppressants.²² A meta-analysis of 31 studies assessing the risk of cancer recurrence with immunosuppressive therapies across immune-mediated diseases also found no difference by medication.²³ These findings align with results from retrospective studies finding no association between cancer recurrence and use of anti-TNF biologics ustekinumab, or vedolizumab.^24,25 Furthermore, an interim analysis from the ongoing prospective SAPPHIRE registry on the safety of immunosuppression in IBD patients with a history of cancer (n=305), with a median follow-up period of 4.8 years, found no significant association between receipt of immunosuppression and incident cancer.²⁶

What to do: Active Cancer and IBD therapy

In most patients with IBD and active cancer, it is recommended to stop thiopurines (see Table 1). There is insufficient data for newer IBD therapies (vedolizumab, ustekinumab, JAK inhibitors), thus patients should be assessed on a case-by-case basis. In collaboration with the oncologist, it is reasonable to stop IBD therapy during the active cancer phase.

Specialized Management of IBD Based on Type of Cancer Therapy

GI toxicity associated with checkpoint inhibitors are often managed with medications used in IBD, so for patients at high risk for complications from IBD and high risk of progression/death from not being treated with checkpoint inhibitors, consider continuing biologic therapy.^3,27

Given that chemotherapy is often associated with remission or reduced IBD activity, stopping IBD therapy can be considered to avoid excess immunosuppression. Flares are associated with hormone deprivation therapy, but there is little guidance available with respect to management.^3,27

For patients receiving radiation therapy, associated toxicity is often minor and manageable, therefore radiation therapy should not be withheld for patients with controlled IBD. Rather it is recommended to consider ways to minimize the risk of GI toxicity, including newer techniques that limit intestinal radiation exposure.^28,29

What to do: History of Cancer and IBD therapy

In terms of what to do with IBD therapy for a patient with a history of cancer, the guidelines and literature summarized in Table 2 indicate it is generally acceptable to use most advanced therapies, but data are limited, particularly for JAK inhibitors. Anti-TNFs and JAK-inhibitors have black box warnings so it may be advisable to avoid their use in cancers with which they have been associated.

Conclusions

In conclusion, the data on cancer in IBD are limited. In practice, treatment decisions must weigh the risks and benefits, consider the natural history of the cancer based on type/stage, time-elapsed since cancer, cancer status and IBD prognosis, and prioritize treatment of the active cancer in most cases.

The available data do not support active or past cancer as a contraindication to biologic or small molecule therapy but withholding immunosuppressive IBD therapy is reasonable in certain scenarios, including the active phase of cancer. Importantly, coordination with the oncologist is crucial in all cases to address nuances given data limitations.

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Clinical Case

Sarah is a 27-year-old patient with known history of ulcerative colitis (UC). She presented at age 16 with moderate UC with a partial response to steroids and 5-ASA. Biologic therapy was recommended but her parents were hesitant and saw several specialists prior to starting infliximab in combination with methotrexate (MTX), requiring a prolonged steroid taper.

She had a good response to infliximab but over time required dose escalation; MTX was discontinued after 1 year due to nausea. She had a flare of her disease with a secondary loss of response with antibodies to infliximab (ATI) at age 20. She was then started on ustekinumab as part of a clinical trial. She responded to therapy, remained on ustekinumab (UST) 90 mg every 8 weeks, and achieved remission (clinical, biochemical, and endoscopic).

She calls your office and speaks to the nurse to let you know that she has been diagnosed with breast cancer and is waiting for her appointment at the cancer clinic. She wants to know if she should stop her UST.

Commentary

• The majority of gastroenterologists would recommend continuation of UST.
• Whether to stop IBD treatment will come down to a case-by-case discussion with the oncologist. For example, if the patient has active advanced cancer, outcome is mainly determined by their cancer, with consideration of quality of life with IBD, so it is important to look at the full clinical picture.
• If a patient has active cancer, oncologists are usually very reluctant to initiate anything that could perturb the immune system and are more likely to wait until cancer therapy is completed.

Case Evolution

The IBD nurse (in consultation with you) recommends no treatment change and books Sarah for a clinic visit with you. Her labs and fecal calprotectin (FCP) are normal, and you discuss the benefits and risks of continuing versus stopping therapy. Specifically, you discuss that stopping therapy will increase her risk of flaring and next steps may be impacted by her cancer treatment plan.

She undergoes a lumpectomy and axillary lymph node (LN) sampling. She is estrogen receptor (ER)/progesterone receptor (PR) negative, and HER2 negative (triple negative), but since the tumor is small without spread, chemotherapy is not recommended. She is reassured and remains on UST through treatment. Her FCP remains normal.

She moves out of province for employment and stops all medications. A year ago, she had a flare of her disease and started on upadacitinib as she wanted to avoid prednisone for induction. She had a good response and was maintained on 30 mg daily.

She then discovers that she has recurrent breast cancer and promptly moves back to your city to be closer to family. You receive an urgent referral to help manage her IBD while she undergoes assessment and treatment of her recurrent malignancy. You book her for your next available clinic spot.

Commentary

• The majority of gastroenterologists would continue upadacitinib, while some would switch to ustekinumab or vedolizumab.

Case Evolution

You continue upadacitinib while she undergoes assessment by the cancer clinic. Complete blood count (CBC) and FCP are normal. As part of her malignancy work-up, it becomes clear that she will require chemotherapy, including cyclophosphamide and doxorubicin.

Commentary

• Most gastroenterologists would stop upadacitinib and watch for flare (symptoms and biomarkers), while also discussing the case with the oncologist.
• Collaboration with oncologists and open discussion with patients is crucial, as there are many case-specific considerations, particularly given the limited data and guidance available

Case Evolution

You discuss the case with the oncologist and due to the interaction of upadacitinib with her chemotherapy regimens, you stop upadacitinib. You book her for a clinic visit to discuss next steps

Commentary

• Most gastroenterologists would wait and watch for flare (FCP every 3 months), as she may remain in remission while on chemotherapy.

Commentary

You decide (with the patient and oncologist) to not start therapy while on chemotherapy. Fortunately, she remains well with FCP remaining <250 during her treatment. She completes the regimen and returns to you for follow-up; Hb 119, CRP 0.5, FCP 190.

• The majority of gastroenterologists would not start maintenance therapy post-chemotherapy, only starting biologic therapy if FCP increases.
• It is important not to assume patients’ need to return to the same therapy they were on before chemotherapy.

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References

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2. Murthy SL. Tandon P, Matthews P, et al. A Population-based matched cohort study of digestive system cancer incidence and mortality in individuals with and without inflammatory bowel disease. Am J Gastroenterol. 2024;119(11):2275–87.
3. Axelrad JE, Hashash JG, Itzkowitz SH. AGA clinical practice update on management of inflammatory bowel disease in patients with malignancy. Clin Gastroenterol Hepatol. 2024;22(7):1365–72.
4. Lemaitre M, Kirchgesner J, Rudnichi A, et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA. 2017;318(17):1679–86.
5. Chupin A, Perduca V, Meyer A, et al. Systematic review with meta-analysis: comparative risk of lymphoma with anti-tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2020;52(8):1289–97.
6. Long MD, Martin CF, Pipkin CA, et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology. 2012;143(2):390–99.
7. Pasternak B, Svanström, H, Schmiegelow K, et al. Use of azathioprine and the risk of cancer in inflammatory bowel disease. Am J Epidemiol. 2013;177(11):1296–305.
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13. National Cancer Institute. Immune checkpoint inhibitors. Available at: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/checkpoint-inhibitors. Accessed February 2025.
14. Meserve J, Facciorusso A, Holmer AK, et al. Systematic review with meta-analysis: safety and tolerability of immune checkpoint inhibitors in patients with pre-existing inflammatory bowel diseases. Aliment Pharmacol Ther. 2021;53(3):374–82.
15. Dougan M, Want Y, Rubio-Tapia A, et al. AGA clinical practice update on diagnosis and management of immune checkpoint inhibitor colitis and hepatitis: expert review. Gastroenterology. 2021;160(4):1384–93.
16. Axelrad JE, Fowler SA, Friedman S, et al. Effects of cancer treatment on inflammatory bowel disease remission and reactivation. Clin Gastroenterol Hepatol. 2012;10(9):1021–7.e1.
17. Koc OM, van Kampen RJW, van Bodegraven AA. Cancer-associated chemotherapy induces less IBD exacerbations and a reduction of IBD medication afterwards. Inflamm Bowel Dis. 2018;24(7):1606–11.
18. Axelrad JE, Bazarbashi A, Zhou J, et al. Hormone therapy for cancer is a risk factor for relapse of inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2020;18(4):872–80.
19. Trotta M, Patel KR, Singh S, et al. Safety of radiation therapy in patients with prostate cancer and inflammatory bowel disease: a systematic review. Pract Radiat Oncol. 2023;13(5):454–65.
20. Feagins LA, Kim J, Chandrakumaran A, et al. Rates of adverse IBD-Related outcomes for patients with IBD and concomitant prostate cancer treated with radiation therapy. Inflamm Bowel Dis. 2020;26(5):728–33.
21. Gnanapandithan K, Stuessel LG, Shen B, et al. Pelvic radiation therapy increases risk of pouch failure in patients with inflammatory bowel disease and ileal pouch. Dig Dis Sci. 2024;69(9):3392–401.
22. Beaugerie L, Carrat F, Colombel J-F, et al. Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer. Gut. 2014;63(9):1416–23.
23. Gupta A, Peyrin-Biroulet L, Ananthakrishnan AN. Risk of cancer recurrence in patients with immune-mediated diseases with use of immunosuppressive therapies: an updated systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2024;22(3):499–512.
24. Hong SJ, Zenger C, Pecoriello J, et al. Ustekinumab and vedolizumab are not associated with subsequent cancer in ibd patients with prior malignancy. Inflamm Bowel Dis. 2022;28(12):1826–32.
25. Holmer AK, Luo J, Russ KB, et al. Comparative safety of biologic agents in patients with inflammatory bowel disease with active or recent malignancy: a multi-center cohort study. Clin Gastroenterol Hepatol. 2023;21:1598–606.e5.
26. Itzkowitz SH, Jiang Y, Villagra C, et al. Safety of immunosuppression in a prospective cohort of inflammatory bowel disease patients with a history of cancer: SAPPHIRE registry. Clin Gastroenterol Hepatol. 2024. https://doi.org/10.1016/j.cgh.2024.05.006.
27. Gordon H, Biancone L, Fiorino G, et al. ECCO guidelines on inflammatory bowel disease and malignancies. J Crohns Colitis. 2023;17(6):827–54.
28. Bodofsky ES, Freeman RH, Hong SS, et al. Inflammatory bowel disease-associated malignancies and considerations for radiation impacting bowel: a scoping review. J Gastro Oncol. 2022;13(5):2565–82.
29. Broussard D, Rivière P, Bonnet J, et al. Impact of abdominal or pelvic radiotherapy on disease activity in inflammatory bowel disease: a multicentre cohort study from the GETAID. Aliment Pharmacol Ther. 2021;53(3):400–9.
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Editor-in-Chief

John K. Marshall, MD MSc FRCPC CAGF AGAF
Professor, Department of Medicine
Director, Division of Gastroenterology
McMaster University
Hamilton, ON

Contributing Author

Fernando Velayos, MD MPH
Chief of Gastroenterology
Kaiser Permanente San Francisco
Director, KP Northern California Inflammatory Bowel Disease Program
Professor of Medicine, University of California
San Francisco, CA

Mentoring in IBD Curriculum Steering Committee

Alain Bitton, MD FRCPC, McGill University, Montreal, QC
Karen I. Kroeker, MD MSc FRCPC, University of Alberta, Edmonton, AB
Cynthia Seow, MBBS (Hons) MSc FRACP, University of Calgary, Calgary, AB
Jennifer Stretton, ACNP MN BScN, St. Joseph’s Healthcare, Hamilton, ON
Eytan Wine, MD PhD FRCPC, University of Alberta, Edmonton, AB

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