Reposted: [Commentary] International Cutting-Edge Advances and Clinical Practice in the Diagnosis and Treatment of Pseudomyxoma Peritonei

Li Yan, et al., Chinese Journal of Gastrointestinal Surgery

Corresponding author: Li Yan

Citation: Li Yan, Wang Hui, Zheng Qingyang, et al. International advances and clinical practice in the diagnosis and treatment of pseudomyxoma peritonei [J]. Chinese Journal of Gastrointestinal Surgery, 2026, 29(4): 445–449. DOI: 10.3760/cma.j.cn441530-20260201-00072.

Authors: Li Yan, Wang Hui, Zheng Qingyang, Fu Yubin

Affiliations: Department of Peritoneal Tumors, Beijing Tsinghua Changgeng Hospital, Tsinghua University; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital of Sun Yat-sen University; Guangdong Provincial Key Laboratory for Research on Colorectal and Pelvic Floor Diseases; Zhongliu Biomedical Innovation Research Institute, Huangpu District, Guangzhou.

Corresponding author: Li Yan, Email: lya03816@btch.edu.cn

Abstract

The academic study of peritoneal pseudomyxoma (PMP) has followed a long and tortuous path, only gradually developing, over the past four decades, a conceptual framework consistent with the core principles of oncology. Consequently, clinical diagnosis and treatment have advanced significantly, culminating in the establishment of an integrated therapeutic paradigm centered on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). This article reviews and synthesizes the cutting-edge research progress in the PMP field presented at the 15th International Conference on Peritoneal Cancer, and, drawing on clinical experience, explores the implications for clinical practice, scientific inquiry, and the development of peritoneal oncology in China, with the aim of providing reference and guidance for the standardized diagnosis and treatment of PMP and for advancing related research in our country.

Pseudomyxoma peritonei (PMP) is a malignant clinical syndrome characterized by the widespread dissemination and peritoneal implantation of mucinous tumor cells and the mucin they produce. Its classic clinical manifestations include mucinous ascites, omental cake formation, peritoneal implantation, and ovarian metastases [1–2]. PMP is a rare disease; in China, its incidence is 25.1 per million [3]. The academic study of PMP has been long and tortuous, only gradually developing a conceptual framework aligned with core oncological principles over the past four decades. Consequently, clinical diagnosis and treatment have advanced significantly, culminating in a comprehensive therapeutic approach centered on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The Peritoneal Surface Oncology Group International (PSOGI) serves as the principal international scholarly organization driving the standardization of PMP research. At its biennial International Peritoneal Cancer Conferences, PMP consistently ranks among the key topics. This article reviews and summarizes the cutting-edge research advances in the field of PMP presented at the 15th International Peritoneal Cancer Conference in October 2025, and, drawing on clinical practice, explores their implications for clinical care, scientific inquiry, and the development of peritoneal oncology in China, with the aim of providing guidance for the standardized diagnosis, treatment, and research of PMP in our country.

I. Molecular Research and the Exploration of Novel Drug Targets

The most common origin of peritoneal mucinous neoplasms (PMP) is appendiceal mucinous tumors, and their molecular profile is critical for precision therapy. Holowatyj et al. at Vanderbilt University Medical Center [4] have proposed a “Cell to Society” research framework and initiated the GAP study (NCT05734430). This study spans multiple levels—molecular, cellular, individual, and community—focusing on genetic mutations and familial hereditary factors in patients with appendiceal tumors, with the aim of identifying susceptibility genes and potential therapeutic targets. Whole-exome sequencing of PMPs originating from the appendix has revealed that alterations in key signaling pathways—including FCGBP, RBFOX1, SPEG, RTK‑RAS, and PI3K‑AKT—are hallmark features of high-grade mucinous carcinomas and represent promising therapeutic targets [5].

This advancement marks a shift in PMP research from morphology‑driven to molecular‑driven approaches. Moving forward, PMP pathology reports will need to integrate the status of key driver genes—such as GNAS and KRAS—to achieve precise alignment between molecular subtyping and clinical diagnostic and therapeutic decision‑making. This will require the establishment of standardized collaborative workflows between pathology departments and molecular diagnostics centers. At the research level, two critical avenues have emerged: first, the development of targeted therapies against pathways like GNAS and RAS, along with exploration of optimal sequencing when combined with CRS plus HIPEC; second, leveraging genetic susceptibility markers to devise early screening and surveillance strategies for high‑risk populations.

II. Clinical Trials of Molecular Targeted Therapy

KRAS and GNAS mutations are frequently observed in appendiceal‑originated PMP. Dr. Barriuso of Spain presented his team’s latest findings: palbociclib, a CDK4/6 inhibitor, demonstrated preliminary efficacy in a phase II trial involving GNAS‑mutant PMP, with significant reductions in carcinoembryonic antigen (CEA) levels in some patients. Meanwhile, Professor Barriuso’s group is advancing the development of a tumor vaccine targeting GNAS‑mutant peptide epitopes; studies have shown that the R201H mutant peptide can elicit robust T‑cell proliferation and immune responses in both PMP patients and healthy donors.

The preliminary efficacy of palbociclib and the exploration of tumor vaccines have challenged the traditional notion that PMP is “unresponsive to medical therapy,” ushering in a new era of precision‑based systemic treatment. In clinical practice, for patients who are ineligible for surgery or who experience rapid recurrence after surgery, genetic testing and proactive enrollment in relevant clinical trials should become standard options. From a research perspective, there is an urgent need to conduct Phase II–III clinical trials to rigorously evaluate the definitive value of targeted and immunotherapies in adjuvant, conversion, or palliative settings, and to identify the patient populations most likely to benefit.

III. Multimodal Imaging and Precise Quantitative Diagnosis

Imaging diagnosis of PMP presents significant challenges; conventional imaging modalities often fail to reliably distinguish tumor tissue from mucinous ascites. Therefore, accurate preoperative assessment of the extent of tumor involvement is a critical basis for guiding therapeutic decision-making.

In Europe, oncologic surgeons commonly rely on MRI for preoperative assessment; studies have demonstrated that MRI can effectively differentiate tumors from mucinous ascites [6]. In contrast, clinical practice in China tends to favor CT imaging. Research by the PMP team at Beijing Aerospace Center Hospital indicates that delayed‑phase CT imaging—acquired 15 minutes after contrast administration—provides clearer delineation of tumor tissue from mucinous ascites compared with standard contrast‑enhanced CT [7]. Meanwhile, research groups in Singapore and the United Kingdom are focusing on multi‑omics approaches to elucidate the molecular mechanisms underlying PMP tumorigenesis and the characteristics of the tumor microenvironment; these findings hold promise for translating into more precise imaging‑based diagnostic tools in the near future.

Taking into account the practical conditions of domestic treatment centers, China should further optimize the preoperative imaging assessment workflow to enable precise calculation of the peritoneal cancer index (PCI). In addition, a standardized multi-omics clinical database for PMP should be established, incorporating key clinical parameters such as the modified PCI score, dynamic changes in tumor markers, intestinal obstruction, and quality-of-life scores. This will help overcome the limitations of the traditional RECIST criteria in evaluating PMP treatment outcomes, thereby providing comprehensive and reliable data support for optimizing therapeutic regimens and conducting high-quality clinical research.

IV. Update of the Clinical Decision-Making Consensus Based on Pathological Features

At this year’s PSOGI, key issues in the diagnosis and management of PMP were thoroughly discussed, and consensus was reached.

1. PMP pathological classification: Currently, the main pathological classification systems include the PSOGI classification and the WHO clinical classification. The latter introduces a category termed “indeterminate malignant potential.” This document discusses the application of these two classification approaches and reaches consensus: preoperatively, the PSOGI classification should be prioritized to guide treatment decisions; if the pathology specimen is insufficient or the classification remains uncertain, cases may be assigned to the WHO “indeterminate malignant potential” category, with a strategy of “intraoperative frozen section analysis combined with postoperative adjuvant therapy tailored to the individual patient.”

2. Surgical management of high-grade appendiceal mucinous neoplasms (HAMN): For patients with HAMN measuring ≤3 cm in diameter, no appendiceal perforation, and negative surgical margins, a simple appendectomy may be performed, followed by imaging surveillance every 6 months. For patients with tumors >3 cm in diameter or those with perforation and positive surgical margins, right hemicolectomy combined with peritoneal exploration and HIPEC is indicated.

3. Treatment strategies after recurrence and timing of re‑operation: Begin with an MDT assessment, involving at least the departments of surgical oncology, medical oncology, and diagnostic imaging. For patients whose lesions are resectable and who are physically fit, prioritize a second CRS combined with HIPEC. For those whose lesions are unresectable or who cannot tolerate surgery, adopt a comprehensive regimen of chemotherapy, targeted therapy, and regular follow-up; consider surgery only once the lesions have been converted to a resectable status.

This updated consensus reflects a growing trend toward increasingly refined and individualized management strategies for PMP. In clinical practice, it is essential to rigorously implement tiered management approaches to prevent under‑ or overtreatment. At the research level, studies should be grounded in data from the Chinese population to validate the applicability of international guidelines within the local context, while also advancing the development of recurrence‑risk stratification models that integrate molecular characteristics, thereby enabling more precise guidance on the selection of postoperative adjuvant therapies.

V. Unveiling the Profound Implications of Basic Pathological Information

The Ki‑67 labeling index is a highly scrutinized molecular marker in pseudomyxoma peritonei (PMP), objectively reflecting tumor proliferative activity and serving as a reliable basis for assessing the rate of tumor growth. A study by French physician Dartigues further underscored the prognostic significance of the PSOGI‑Ki‑67 grading system: even in low‑grade PMP, the 5‑year overall survival rate was 59% among patients with Ki‑67 ≤ 15%, whereas it declined to 38% in those with Ki‑67 > 15% [8]. Our own team’s analysis of PMP patients who have survived for more than 10 years demonstrated that the extent of tumor debulking and histopathological subtype are critical prognostic factors [9].

Radical surgical cytoreduction and precision systemic therapy are critical components of future management for PMP. Clinicians should comprehensively assess pathological subtypes and biomarkers such as the Ki‑67 proliferation index to develop individualized treatment plans; for PMP cases with a low‑grade histologic diagnosis but a high Ki‑67 index, a more aggressive therapeutic strategy than traditionally advocated should be adopted. This has driven an evolution in prognostic models for PMP, shifting from conventional clinicopathological approaches toward integrated clinical–pathological–molecular frameworks; the development and validation of such models represent important avenues for future research.

VI. Optimization of the PMP Prognostic Model and Surgical Clinical Practice

Dr. Martin from the United Kingdom reported on risk factors for recurrence in patients with PMP following CRS plus HIPEC. The team found that incorporating genetic mutation status—such as KRAS, GNAS, and BRAF—into a conventional prognostic model based on clinical–pathological parameters like PCI, histologic subtype, and the extent of tumor debulking significantly improved predictive performance. Meanwhile, Dr. Quenet from France analyzed prognostic factors, treatment strategies, and regimens in recurrent PMP patients, sharing insights and experience regarding the individualized management of this patient population [10]. This year’s PSOGI conference featured a dedicated session on surgical techniques, during which several European surgeons presented approaches and experiences for overcoming challenging aspects of peritoneal tumor surgery, including diaphragmatic and hepatic hilum management, gastrointestinal reconstruction, and systematic clearance of thoracic and pelvic lesions.

Prognostic models that integrate molecular features represent a direct embodiment of the precision medicine paradigm in the surgical management of PMP. Clinically, these models enable more accurate identification of patients at high risk of recurrence—either preoperatively or in the early postoperative period—thereby providing a basis for devising more aggressive adjuvant therapies or implementing closer surveillance strategies. At the research level, developing and validating locally adapted integrated prognostic models using Chinese patient cohorts, and exploring their integration with clinical treatment decision‑making, constitutes a highly valuable line of inquiry. Meanwhile, systematically summarizing and refining individualized diagnostic and therapeutic experiences in recurrent cases represents an important clinical research endeavor in its own right.

VII. A Reassessment of PMP in Medical Oncology

The value of pharmacologic therapy for PMP must be assessed in light of the disease’s unique characteristics. First, unlike peritoneal metastases from other origins, most patients with PMP derive little benefit from systemic chemotherapy; moreover, neoadjuvant treatment with cytotoxic agents alone may even delay surgical intervention. Second, evaluating drug efficacy in PMP poses significant methodological challenges: the RECIST criteria, commonly used for solid tumors, are not suitable for PMP, and clinical assessments often rely on subjective physician judgment, incorporating tumor marker changes, imaging findings, and quality-of-life scores—without a unified, standardized evaluation tool. Finally, improvement in PMP‑specific symptoms should be regarded as a key endpoint in assessing pharmacologic treatment; “obstruction‑free survival” should be recognized alongside “overall survival,” “disease‑free survival,” and “progression‑free survival” as an important outcome measure for evaluating the efficacy of drug therapies in PMP.

Accordingly, clinical management of PMP with medical therapy should adopt a rational and prudent approach: while acknowledging its potential value in precisely identifying patient subgroups and determining the optimal timing for surgery, it is equally important to remain vigilant about the risks associated with its inappropriate use. The appropriate role of pharmacologic treatment should encompass: its use in clinical trials as an adjunct to targeted or immunotherapy; its application as neoadjuvant therapy in patients with unresectable disease; and its utilization as palliative care to alleviate symptoms. Furthermore, establishing a dedicated set of efficacy‑assessment criteria specific to PMP and promoting their widespread adoption and clinical validation constitute one of the key priorities in the current methodological landscape of PMP research.

VIII. Strive to promote the PMP‑based standardized technical system for oncologic surgery.

The development of CRS surgical techniques has reached a mature stage. Both domestic and international guidelines and consensus statements rarely feature fundamental innovations; instead, the focus has shifted to refining procedural details, with the widespread adoption of standardized techniques playing a particularly critical role. At the conference, several clinical studies centered on surgical approaches yielded promising results, with striking rates of complete cytoreduction reported across these trials—findings closely linked to the growing number of surgeons who have undergone rigorous, standardized training in the field of peritoneal cancer treatment. In fact, compared with advancing surgical innovations, promoting standardized CRS protocols is currently far more practical and impactful in the realm of PMP surgical management.

This poses clear requirements for the discipline’s development: prioritizing the establishment and dissemination of a systematic, replicable CRS‑training framework—comprising textbooks, surgical videos, and hands-on mentorship—and ensuring that this practical training system encompasses three core components.

1. Strengthening specialized surgical techniques for peritoneal tumors: These specialized techniques encompass procedures ranging from organ and peritoneal anatomy to organ resection and regional excision, from conventional hemostasis to triple‑layered hemostatic strategies, and from instrument‑based resection to multimodal electrosurgical ablation. At the same time, it is essential to integrate expertise from traditional surgical subspecialties, such as regional multiorgan resections and complex reconstructive techniques. The surgical team must be proficient in a broad spectrum of disciplines, including general surgery, urology, obstetrics and gynecology, vascular and lymphatic surgery, and reconstructive plastic surgery.

2. “One-on-one, hands-on” mentorship: Specialized training for surgeons specializing in peritoneal malignancies must begin with one‑on‑one, hands‑on instruction, strictly following a four‑level progression to progressively advance technical proficiency. Trainees are required to complete a learning curve of approximately 100 CRS plus HIPEC procedures before they can confidently perform such complex operations [11]. The training should progress through three stages—guided learning, supervised learning, and exploratory learning—each representing an essential step in technical development.

3. Strengthen perioperative management: It is essential to take a hands-on, proactive approach to perioperative rehabilitation exercises, thereby minimizing the incidence of serious adverse events. Key preventive measures should focus on complications such as cardiopulmonary dysfunction, venous thromboembolism, stress‑related peptic ulcer bleeding and perforation, severe electrolyte imbalances, and nutritional disorders. Successfully implementing these evidence‑based practices represents a critical priority for clinical research; meanwhile, efficiently and reliably scaling up this standardized technique across healthcare facilities at different levels is the central task for achieving uniform improvements in the quality of diagnosis and treatment.

IX. Establishing and Promoting a Practical and Feasible Specialty Training System

The success rate of PMP diagnosis and treatment is highly dependent on a standardized, multidisciplinary care system that integrates surgical oncology, medical oncology, and tumor hyperthermia with chemotherapy [12]. Internationally, relatively mature specialized training programs for PMP have been established: (1) PSOGI has developed an international training framework across its member countries, featuring standardized textbooks, video‑based surgical tutorials, and hands‑on mentorship by experts; (2) the European Society of Surgical Oncology, with support from PSOGI, has founded the European School of Peritoneal Surface Malignancy, which is primarily responsible for the standardized training of PMP specialists in EU member states.

At present, the PMP training system in Europe has become well‑established and mature, and China’s corresponding training framework is gradually aligning with international standards. To advance the establishment and refinement of a PMP diagnostic and therapeutic training system in China, it will be essential to leverage the leadership of leading clinical centers, foster collaboration among academic societies, and secure policy‑level support. Training should not only cover core surgical techniques but also encompass multidisciplinary team (MDT) workflows, comprehensive patient management and follow‑up, and clinical research methodologies—aiming to cultivate a cadre of subspecialist physicians capable of independently delivering standardized PMP care.

X. Taking PMP as a model, comprehensively advance the development of the discipline of peritoneal oncology. 
The continuous advancement of PMP diagnostic and therapeutic techniques has provided a central driving force for the development of peritoneal oncology, while also enriching the discipline’s conceptual framework. Its core characteristics are reflected in the following five aspects: (1) Peritoneal metastatic cancer exhibits a unique pathogenesis, primarily encompassing the tumor cell selective colonization theory and the encapsulating hyperplasia theory; (2) It displays a characteristic distribution pattern, predominantly involving the diaphragmatic peritoneum, pelvic peritoneum, omentum, mesentery of the small intestine, and the epiploic appendices of the colon; (3) Its clinical manifestations are distinctive, with refractory ascites, intractable abdominal pain, and progressive intestinal obstruction serving as hallmark symptoms; (4) Diagnostic understanding of peritoneal metastatic cancer is unique, as it fundamentally represents regional metastasis rather than widespread systemic dissemination; (5) Peritoneal metastatic cancer calls for a tailored therapeutic strategy; clinically, the peritoneum can be treated as a single organ, with CRS plus HIPEC—integrated surgical‑oncologic therapy—serving as the cornerstone of management [13].

Based on the aforementioned disciplinary characteristics, the development of peritoneal oncology requires establishing an independent peritoneal tumor diagnosis and treatment center, assembling a specialized multidisciplinary team (MDT), conducting basic and clinical research centered on the unique biological behaviors of peritoneal metastases, and building a dedicated patient‑specific clinical database to leverage real-world data for the continuous refinement of diagnostic and therapeutic strategies.

In summary, PMP is a quintessential example of challenging malignant tumors such as peritoneal cancer, and advances in our understanding of this condition, coupled with improvements in diagnostic and therapeutic techniques, directly reflect the overall level of progress in the field of peritoneal oncology. At present, the development of this field in China remains uneven, underscoring the urgent need to strengthen basic research and to promote the widespread adoption of standardized clinical practices.

Conflict of Interest: All authors declare that no conflicts of interest exist.

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