Targeting the right cavities: Localized chemotherapy for abdominal cancers

Systemic chemotherapy can be an ordeal for patients with cancer due to associated adverse effects. However, surgical interventions such as HIPEC (hyperthermic intraperitoneal chemotherapy) and PIPAC (pressurized intraperitoneal aerosol chemotherapy) can create opportunities for targeted application of chemotherapy drugs. Dr Ang Chin Wee, consultant general and colorectal surgeon, Mahkota Medical Centre Malaysia, shared with MIMS Doctor about his experiences with HIPEC and PIPAC in the treatment of abdominal cancers.

1. How long have HIPEC and PIPAC been available treatments in Malaysia?

In private healthcare institutions in Malaysia, HIPEC is available but not yet popularized due to the complexity of the treatment and the intensive resource use. It is quite a common treatment in many developed countries. PIPAC is currently not available in private healthcare institutions apart from Mahkota Medical Centre [as far as is known].

In government healthcare institutions, HIPEC has been available since 2018; PIPAC, since 2019. Likewise, the practice [of PIPAC] is limited due to resource limitations and the lack of skilled, well-trained surgeons specializing in this [method].

2. How are HIPEC and PIPAC performed? What is the purpose of their unique delivery mechanisms?

In HIPEC, surgeons will firstly remove most—if not all—of the visible tumours in the abdomen, especially the lining of the abdomen (peritoneum). Heated chemotherapy fluids are then administered into the abdominal cavity to continuously wash the entire abdomen for 30 to 90 minutes. The abdomen is then closed and surgery is completed. [Both] the heating and continuous direct wash increase the penetration and cytotoxic effects of chemotherapy against residual cancer cells in the abdominal cavity.

For PIPAC, laparoscopy, which is a minimally invasive surgery, is performed first; the abdominal cavity is infused with carbon dioxide under pressure so that the organs and tumours can be examined via a camera. Chemotherapy drugs are then aerosolized with a special device and infused into the abdomen during the laparoscopy. This way, the distribution and penetration of chemotherapy drugs are improved.

3. How do HIPEC and PIPAC compare to conventional chemotherapy in efficacy and safety?

For peritoneal cancers, HIPEC and PIPAC have both been shown to have better distribution and penetration directly into cancer cells, which therefore creates a superior cytotoxic effect. Conventional chemotherapy, which is administered intravenously, is known to have poor efficacy against peritoneal tumours.

Given that the mode of the drug delivery is different, the safety/ adverse effect profiles between HIPEC/ PIPAC and conventional chemotherapy are different. HIPEC and PIPAC are surgeries, and thus surgical risks would be taken into consideration.

With regards to specific adverse effects related to chemotherapy, conventional systemic chemotherapy has numerous systemic side effects, whereas the absorption of chemotherapy from HIPEC/ PIPAC into the [patient’s] systemic circulation is very low and therefore, causes minimal systemic adverse effects [in comparison].

4. How invasive are HIPEC and PIPAC versus conventional chemotherapy?

HIPEC and PIPAC are invasive because they are part of surgical procedures. HIPEC especially involves major surgery to remove most if not all the visible cancers in the abdomen, while PIPAC is less invasive than HIPEC as it is delivered laparoscopically. Conventional chemotherapy is delivered via the intravenous route and represents the least invasive mode.

5. At what stage of disease would HIPEC or PIPAC be advised?

HIPEC and PIPAC are specifically considered for peritoneal cancers. Peritoneal cancers are a specific group of cancers usually spread from other primary cancer sites, including colorectal cancer, gastric cancer, and ovarian cancer.

In colorectal cancer, 5 to 10 percent of patients are diagnosed with peritoneal cancer (stage 4) on initial presentation, with nearly 60 percent of these patients having no other systemic disease elsewhere. Moreover, peritoneal spread (metastasis) has been diagnosed in 20 to 30 percent of patients during follow-ups after previous cancer surgery. Of these, 25 percent have recurrent disease only in the peritoneal cavity.

Therefore, HIPEC/ PIPAC treatments are generally suitable for stage 4 patients with peritoneal metastases. However, there are other cancers that originate primarily from the peritoneum, such as mesothelioma and primary peritoneal cancer, which could also be treated with HIPEC/ PIPAC.

For colorectal cancer, conventional chemotherapy is usually recommended for high-risk stage 2 patients, as well as all stage 3 and 4 patients. An increasing number of studies has also shown that HIPEC can be performed as prophylaxis for high-risk tumours, such as in cases with perforated stage 2 or 3 tumours or locally advanced tumours, to prevent recurrence.

6. Do patients need to return for regular treatment sessions?

Depending on the primary disease, HIPEC is usually a one-off treatment during surgery. However, patients may need to undergo conventional chemotherapy either before or after HIPEC to prevent systemic cancer spread.

For PIPAC, the treatment cycle is usually every 6–8 weeks in conjunction with conventional systemic chemotherapy. 

7. Are there patient groups for which HIPEC and PIPAC are not advisable?

HIPEC essentially involves major surgery, and therefore, unsuitable for elderly patients or those who are unfit to undergo major surgery. Patients who have a bowel obstruction and very extensive disease would be advised against undergoing HIPEC/ PIPAC.

8. What papers would you recommend for further understanding of these techniques?

Here is a list of papers for further information:

• HIPEC for colorectal cancer: Vassos N, Piso P. Metastatic colorectal cancer to the peritoneum: Current treatment options. Curr Treat Options Oncol 2018;19(10):49.
• HIPEC for gastric cancer: Manzanedo I, et al. Review of management and treatment of peritoneal metastases from gastric cancer origin. J Gastrointest Oncol 2021; 12(Suppl 1):S20–S29.
• HIPEC for ovarian cancer: Huo YR, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2015;41(12):1578–1589.
• PIPAC: Alyami M, et al. Pressurised intraperitoneal aerosol chemotherapy:  rationale, evidence, and potential indications. Lancet Oncol 2019;20(7):e368–e377.