Good Doctor · Hyperthermic Perfusion | Literature Brief Review | Current Clinical Applications and Future Prospects of CRS + HIPEC in the Treatment of Pseudomyxoma Peritonei (PMP)

In 2012, Chua, Sugarbaker, and colleagues reported the results of a large, multicenter, international clinical study involving 2,298 patients: for PMP treated with CRS plus HIPEC, the median overall survival (mOS) was 196 months (16.3 years), and the median progression-free survival (mPFS) was 98 months (8.2 years); 10‑year and 15‑year survival rates were 63% and 59%, respectively. The rates of grade 3–4 complications and perioperative mortality were 24% and 2%, respectively [6]. More recently, a multicenter real-world study conducted in China analyzed outcomes in 940 patients with PMP who underwent CRS plus HIPEC; the median overall survival (mOS) was 116.7 months (9.7 years). However, these results were significantly lower than those reported by Chua and Sugarbaker, likely attributable to a higher proportion of patients with a high PCI score (≥20)—695 cases, or 73.9%—and suboptimal completeness of CRS procedures (CC‑2/3, 434 cases, or 46.2%) [7].

Furthermore, pathological stratification is also associated with differences in survival. Ronnett et al. reported in 2001 that a small‑sample (n=109) stratified analysis revealed 5‑year overall survival (OS) rates of 75%, 50%, and 14% for low‑grade (DPAM), intermediate‑grade (PMCA‑I/D), and high‑grade (PMCA), respectively [8]. Yonemura et al. reported in 2025 that a large‑sample (n=1117) stratified analysis demonstrated 10‑year overall survival rates of 86.9%, 63.7%, 32.2%, and 10.1% for acellular mucinous tumors (AM), low‑grade mucinous peritoneal carcinomas (LGMCP), high‑grade mucinous peritoneal carcinomas (HGMCP), and high‑grade mucinous carcinomas with signet‑ring cells (HGMCP‑S), respectively [9].

In recent years, a significant development has been the international community’s efforts to standardize HIPEC protocols and techniques. The PSOGI consensus supports the use of HIPEC in patients with peritoneal malignant mesothelioma following CRS. This consensus recommends cisplatin (75 mg/m²) combined with mitomycin C (12.5 mg/m²) or high-dose mitomycin C (35 mg/m²) as key drug choices and dosing regimens for current clinical practice and future comparative studies [3, 14], and these are also the strongly recommended drug choices and dosing regimens in the latest Chinese expert consensus [15].

Currently, the standardized treatment approach for PMP is high-quality CRS combined with standardized HIPEC, encompassing standardized temperature control, standardized drug selection and dosing, and standardized perioperative management.

Precisely select patients, rather than applying the same CRS plus HIPEC to everyone in a one-size-fits-all manner. The core objective moving forward will be to determine “who can benefit from CRS plus HIPEC,” rather than merely addressing whether “CRS plus HIPEC can be performed” [16]. Treatment algorithms will increasingly favor stratified management of PMP based on biological subtypes:

[Low-Risk PMP]

Patients who are diagnosed as low-risk and asymptomatic may be managed with clinical observation and regular follow-up.

Perform limited minimally invasive surgery when necessary.

CRS plus HIPEC is performed when disease progression or significant tumor burden occurs.

[Medium Risk PMP]

CRS + HIPEC (standard treatment)

Individualized Perioperative Systemic Therapy

Close Follow-up Observation and Surveillance

[High-grade / Aggressive PMP]

Systemic therapy + molecular profiling

Adopt a conversion therapy approach whenever possible.

For patients who have been rigorously screened and found to be responsive to conversion therapy, CRS plus HIPEC is performed.

Molecular profiling (PMP molecular profiling) will become increasingly important.

PMP is not a single biological disease; it involves mutations in pathways such as the Kirsten rat sarcoma viral oncogene homolog (KRAS), the GNAS complex locus (GNAS), and the tumor protein P53 gene (TP53), as well as other molecular alterations [16]. Molecular subtyping will help define the tumor’s biological characteristics and may ultimately guide treatment intensity and the selection of systemic or targeted therapies.

Future models may integrate histopathological classification, the peritoneal cancer index (PCI), the cytoreduction score (CC), molecular subtyping, and circulating tumor biomarkers—rather than relying solely on anatomical criteria to guide treatment decisions.

Liquid biopsy and circulating tumor DNA (ctDNA) monitoring

A particularly promising future direction is circulating tumor DNA (ctDNA) [17]. Following CRS plus HIPEC, routine CT imaging and tumor biomarkers may fail to determine: 1) whether tumor lesions have been completely eradicated; 2) the presence of microscopic residual disease detectable only under the microscope; and 3) the early detection of minimal residual disease (MRD) that carries a potential risk of recurrence.

ctDNA holds promise as a molecular assay for detecting minimal residual disease (MRD). Consequently, the future monitoring paradigm may evolve to: CRS + HIPEC → ctDNA/MRD monitoring → molecular‑level detection of early recurrence → early intervention. This approach could be particularly valuable in high‑grade or aggressive PMP.

Combined immunotherapy and HIPEC treatment

At present, immunotherapy is not a substitute for CRS plus HIPEC in the treatment of PMP. Instead, the central question for the future is whether HIPEC can be employed as an “immune‑priming” strategy [18, 19, 20].

Cancer cell death induced by hyperthermia combined with chemotherapy can lead to the release of tumor antigens, which in turn activates dendritic cells, triggers inflammatory signaling pathways, and elicits immunogenic cell death, ultimately promoting T‑cell recruitment and activation. This provides a theoretical rationale for exploring combination therapies such as CRS plus HIPEC plus immune checkpoint inhibition (e.g., anti‑PD‑1/PD‑L1 antibodies), particularly in patients who have been screened using molecular biomarkers. At present, this approach remains in the clinical research stage and has not yet been established as an established standard of care.

New intraperitoneal drug delivery system

Another future direction is to overcome the limitations of using only liquid solutions as carriers for HIPEC. Potential technologies include pressurized intraperitoneal aerosol chemotherapy (PIPAC), drug-eluting nanoparticles, liposomal chemotherapy, targeted intraperitoneal delivery, and image-guided regional therapy, among others [21].

More advanced HIPEC techniques [22, 23]

The next-generation HIPEC system should feature the following capabilities: real-time temperature mapping (i.e., live visualization of the thermal distribution within the cavity), automated flow control, uniform drug distribution with no dead spots, reduction of extracorporeal dead space volume, computerized perfusion monitoring, and standardized treatment documentation.

This point is particularly important, because HIPEC is by no means as simple as “infusing chemotherapy drugs into the peritoneal cavity.” Its therapeutic efficacy depends on: temperature × drug concentration × treatment duration × uniformity of distribution × depth of tissue penetration.

Future systems, leveraging more sensitive sensors and AI‑based control algorithms, will maintain a more uniform treatment environment, thereby reducing under‑treatment or overheating.

01 Paradigm Shift in PMP Treatment 
 

02 Future PMP Treatment Steps

(The future PMP treatment algorithms)