The study, led by Shichuan Tang, Tingfeng Huang, and colleagues at the Mengchao Hepatobiliary Hospital of Fujian Medical University and collaborating institutions across China, focused on a pathological feature called microvascular invasion, or MVI. MVI refers to the presence of tumor cell clusters within small blood vessels in the liver tissue surrounding the main tumor mass. It is a subtle phenomenon, invisible on imaging scans and detectable only when a pathologist examines the resected specimen under a microscope. Yet its clinical significance is enormous: MVI is widely regarded as one of the strongest predictors of early recurrence after liver cancer surgery, because tumor cells that have already entered the vasculature are, in effect, seeds that may have scattered throughout the liver before the operation even began.

What makes the new research particularly timely is its patient population. All 101 individuals in the study had initially unresectable hepatocellular carcinoma and underwent hepatectomy only after receiving conversion therapy consisting of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies. TKIs are oral targeted drugs that interfere with signaling pathways driving tumor growth and angiogenesis, while anti-PD-1 antibodies are immune checkpoint inhibitors that release the molecular brakes on T cells, allowing the immune system to attack cancer cells. This combination has rapidly become one of the most widely used conversion regimens worldwide, but a key question has lingered: once these drugs have transformed an inoperable tumor into an operable one, what determines the patient’s long-term fate?

To answer that question, the research team applied a severity grading system for MVI that divides patients into three categories. Patients in the M0 group showed no microvascular invasion at all. Those in the M1 group had between one and five MVI foci located within one centimeter of the tumor. The M2 group, the most severe category, included patients with more than five foci within one centimeter of the tumor and/or any invasive foci found more than one centimeter away, a finding indicating that tumor cells had traveled further into the surrounding liver. This graded approach goes beyond the simple binary question of whether invasion is present or absent, capturing instead a spectrum of biological aggressiveness.

The distribution of patients across these categories was itself informative. Of the 101 patients, 62 fell into the M0 group, 21 into M1, and 18 into M2, meaning that nearly four in ten patients who achieved successful conversion therapy still harbored microscopic evidence of vascular spread. The researchers then tracked two critical endpoints: recurrence-free survival (RFS), which measures how long patients remain free of detectable cancer after surgery, and overall survival (OS), which tracks how long patients live. The differences that emerged between the groups were dramatic and statistically significant.

At two years after surgery, the recurrence-free survival rate was 57.8 percent for patients with no microvascular invasion, 43.7 percent for those with mild invasion, and just 11.1 percent for those with severe invasion. Overall survival followed a similarly sobering gradient: 92.9 percent at two years for the M0 group, 84.7 percent for the M1 group, and only 40.1 percent for the M2 group. In other words, a patient whose resected specimen showed extensive microscopic vascular invasion was roughly four times more likely to have died within two years than a patient whose specimen was clean, despite both having undergone the same operation after the same class of drug therapy.

To ensure these associations were not confounded by other clinical variables, the team performed multivariable analyses, statistical models that adjust for competing risk factors. The results confirmed the independent prognostic power of MVI grading. Compared with the M0 group, patients in the M1 category had a 1.81-fold higher risk of recurrence (hazard ratio 1.81, 95 percent confidence interval 1.17 to 2.11), while those in the M2 category faced a 3.98-fold higher risk (95 percent confidence interval 1.91 to 8.29). The survival gap was even starker: M1 status carried a 3.57-fold higher risk of death (95 percent confidence interval 1.05 to 13.33), and M2 status a 12.22-fold higher risk (95 percent confidence interval 3.87 to 38.61). These hazard ratios, all statistically significant, establish MVI severity as one of the dominant determinants of outcome in this population.

The biological story behind these numbers is worth unpacking. Conversion therapy with TKIs and anti-PD-1 antibodies can produce remarkable shrinkage of the visible tumor, sometimes to the point where surgeons can achieve what appears to be a complete resection with clear margins. But the drugs act primarily on the main tumor mass and its immediate microenvironment. Tumor cell nests that have already detached into small portal or hepatic venules may be less susceptible to the same immune attack, shielded within vascular spaces or already lodged in distant liver parenchyma. The graded MVI system effectively measures how far this occult dissemination has progressed. A few foci close to the tumor suggest early, limited spread; numerous foci or foci beyond one centimeter suggest a tumor that has been seeding the liver more aggressively, even while responding to therapy on the surface.

The clinical implications of the study are substantial. Postoperative management of converted HCC patients has long been a gray zone: some patients receive adjuvant therapy, others undergo intensified surveillance, and the decision-making has often rested on tumor size, number, and response to preoperative treatment rather than on pathology of the resected specimen. The new findings suggest that MVI grading should become a central pillar of postoperative risk stratification. A patient classified as M0 might be counseled that their two-year survival odds exceed 90 percent and could potentially be spared intensive adjuvant regimens, whereas an M2 patient, with a two-year survival rate of roughly 40 percent, would be an obvious candidate for aggressive adjuvant treatment, close-interval imaging surveillance, and enrollment in clinical trials of postoperative immunotherapy.

Several caveats deserve mention. The study involved 101 patients drawn from a multicenter database, a respectable but ultimately modest sample size, and the wide confidence intervals around some of the survival hazard ratios reflect the limited number of events in the smaller M1 and M2 groups. The analysis was retrospective in design, and the grading of MVI, while standardized, depends on the thoroughness of pathological sampling of the resected specimen. Nonetheless, the consistency of the signal across both recurrence and survival endpoints, and its persistence after multivariable adjustment, lends considerable weight to the conclusion. As conversion therapy with TKIs and anti-PD-1 antibodies continues to expand globally, offering curative surgery to patients who once had no surgical option, this study provides a practical, pathology-based compass for navigating what comes after the operation. The message is clear: even after the most successful drug-induced transformation, the microscope still holds the final word on a patient’s prognosis.

Subject of Research: Severity grading of microvascular invasion as a prognostic marker after conversion therapy and hepatectomy for unresectable hepatocellular carcinoma

Article Title: Severity grading of microvascular invasion predicts oncological outcomes following hepatectomy for unresectable hepatocellular carcinoma converted by tyrosine kinase inhibitors plus anti-PD-1 antibodies

Article References: Tang, S., Huang, T., Zheng, X., Cui, Z., Liu, D., Peng, S., Kong, J., Luo, C., Fan, R., Guo, L., Zhang, K., Lin, Q., Fu, J., Zheng, L., & Zeng, Y. (2026). Severity grading of microvascular invasion predicts oncological outcomes following hepatectomy for unresectable hepatocellular carcinoma converted by tyrosine kinase inhibitors plus anti-PD-1 antibodies. BMC Cancer. https://doi.org/10.1186/s12885-026-17057-0

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17057-0

Keywords: hepatocellular carcinoma, microvascular invasion, conversion therapy, tyrosine kinase inhibitors, anti-PD-1 antibodies, hepatectomy, recurrence-free survival, overall survival, prognosis, liver cancer, immunotherapy, risk stratification

Conversion therapy, sometimes called downstaging therapy, refers to the use of systemic drugs, local regional treatments, or both, to shrink initially unresectable tumors until they become candidates for curative surgery. The concept has gained momentum in recent years as systemic treatments have improved dramatically. Combinations of anti-angiogenic targeted drugs and immune checkpoint inhibitors now achieve objective response rates of around 30 percent in advanced or unresectable hepatocellular carcinoma, while local therapies such as transarterial chemoembolization (TACE), hepatic artery infusion chemotherapy (HAIC), and radiation therapy have become more effective at reducing tumor volume and controlling tumor thrombus within blood vessels. When these approaches succeed, patients who once had no surgical option can undergo resection, and studies suggest their post-surgical survival can approach that of patients whose tumors were resectable from the start.

To understand how this evolving paradigm is actually being applied, a team led by investigators from the National Cancer Center in Beijing and the China Liver Cancer Study Group Young Investigators conducted a structured survey between January and July 2024. The researchers distributed questionnaires to physicians meeting strict criteria: they had to work at a tertiary hospital, practice in hepatobiliary surgery or interventional radiology, hold the rank of associate chief physician or above, see at least five new hepatocellular carcinoma patients per month, and serve as primary decision-makers for conversion therapy. Ultimately, 120 valid responses were collected from 79 tertiary hospitals across 20 provinces. Nearly 70 percent of respondents were hepatobiliary surgeons and the remainder were interventional radiologists, reflecting the two specialties that dominate conversion therapy decision-making in China’s disease-centered, surgery-led multidisciplinary model.

The headline finding is striking: physicians reported that approximately 51 percent of newly diagnosed patients with stage Ib to IIIa disease, according to the China Liver Cancer Staging (CNLC) system, were selected for conversion or downstaging treatment with the goal of eventual resection. The proportion was highest among patients with stage IIb and IIIa tumors, of whom 52 percent and 59 percent respectively received such treatment. In other words, more than half of newly diagnosed patients in these intermediate stages are now being routed through a treatment pathway designed to convert an impossible operation into a possible one. This represents a profound shift from a decade ago, when most of these patients would have gone directly to palliative local or systemic therapy without any surgical ambition.

Which patients do physicians choose for this aggressive approach? The survey identified three dominant factors. Portal vein tumor thrombus (PVTT)—the invasion of tumor into the main blood vessel draining the liver—was considered by 97 percent of respondents, making it the most widely weighed criterion. Future liver remnant volume, the amount of healthy liver that would remain after resection, and Child–Pugh liver function classification were each cited by 90 percent. Tumor number followed at 89 percent, with extrahepatic metastasis and tumor size each at 88 percent. When physicians rated the importance of each factor on a seven-point scale, extrahepatic metastasis and portal vein tumor thrombus received the highest weights, with 82 percent and 78 percent of relevant respondents scoring them six or above. The typical candidate for conversion therapy, according to the respondents, had Child–Pugh A liver function or well-preserved B7 function, a tumor larger than five centimeters, good performance status, and early or moderate portal vein tumor thrombus.

The prominence of portal vein tumor thrombus reveals a genuine philosophical evolution in the field. Under the Barcelona Clinic Liver Cancer (BCLC) staging system, used widely in Europe and the United States, hepatocellular carcinoma with portal vein invasion is classified as advanced stage C, and systemic therapy is recommended as the only option. Japanese guidelines take a middle path, recommending surgery when thrombus has not invaded first-order portal vein branches. Chinese guidelines classify vascular invasion as stage IIIa and list TACE with or without systemic therapy as the primary treatment, followed by surgery. Yet 72 percent of surveyed physicians considered patients with Vp1/2 thrombus—where tumor invasion remains limited—suitable for conversion therapy, reflecting what the authors describe as a shift from a narrow to a broad concept of conversion intent. The rationale is twofold: modern drug combinations can shrink both the tumor and the thrombus, facilitating complete resection, and the treatment period itself helps identify biologically aggressive tumors that would recur quickly after surgery, sparing those patients a futile operation.

When it comes to the regimens themselves, the survey found overwhelming preference for combination therapy. Approximately 73 percent of patients received a combination of local treatment with targeted therapy and immunotherapy. Within this group, 29 percent received targeted plus immunotherapy with TACE, 26 percent with HAIC, and 18 percent with both local modalities together. Only about 10 percent of physicians used systemic therapy alone. Interventional radiologists were significantly more likely than surgeons to favor quadruple combinations including both TACE and HAIC, while surgeons more often selected systemic therapy alone. The biological logic of these combinations is compelling: anti-angiogenic drugs inhibit the new vessel formation that TACE can paradoxically stimulate, while TACE itself increases expression of immune-suppressive molecules such as CTLA-4 and PD-L1, which immune checkpoint inhibitors then block, restoring anti-tumor immunity. A recent meta-analysis covering 2007 to 2024 reported conversion rates of 5 to 28 percent for systemic therapy alone, 13 to 33 percent for combined local and systemic therapy, and peaks around 35 percent for regimens combining lenvatinib, PD-1 inhibitors, and local treatment.

Drug selection showed a clear winner. Lenvatinib combined with immunotherapy was the preferred systemic backbone for 64 percent of physicians, with 49 percent using the original formulation and 13 percent using generics. The next most popular regimens—bevacizumab biosimilar with sintilimab, and bevacizumab with atezolizumab—trailed far behind at around 11 percent. Physicians explained their choices through a hierarchy of priorities: a higher objective response rate was the foremost consideration for 83 percent, followed by rapid onset of response at 68 percent, adherence to guidelines and consensus documents at 63 percent, and lower tumor progression rate at 58 percent. Lenvatinib-based regimens scored well across efficacy, safety, and practical metrics, including lower bleeding risk, shorter preoperative drug discontinuation times, and easier dose adjustment—considerations that matter enormously when the endpoint is not merely tumor control but a safe operation.

What defines success, and what happens after it? Physicians ranked R0 resectability—the ability to remove all visible tumor with clear margins—as the most important criterion for successful conversion, selected by 96 percent and weighted most heavily. Tumor thrombus regression, adequate future liver remnant volume, achievement of complete or partial radiological response, and tumor stability for more than two months followed. The survey’s estimated overall conversion success rate was approximately 32 percent, but the figure fell sharply with disease stage: 57 percent for stage Ib patients, 42 percent for stage IIa, 35 percent for stage IIb, 28 percent for stage IIIa, and just 15 percent for stage IIIb, where extrahepatic metastases make radical surgery far harder to achieve. Among patients who converted successfully, about 57 percent went on to surgery, and 79 percent of those surgical patients received postoperative adjuvant therapy, most commonly systemic treatment with targeted and immunotherapy combinations.

The authors are candid about the limitations of their work. All surveyed hospitals were tertiary referral centers, so the findings may not generalize to community hospitals. The conversion success rates reflect physician estimates rather than audited patient-level data, and the anonymous cross-sectional design precluded assessing test–retest reliability or comparing respondents with non-respondents. Still, the survey’s value lies in mapping real-world clinical attitudes at a moment when the evidence base consists largely of retrospective studies and small single-arm trials, with randomized controlled data still scarce. By documenting that over half of newly diagnosed intermediate-stage patients in China are now considered candidates for conversion therapy, and by identifying the criteria and regimens that dominate practice, the study provides a foundation for the multicenter collaboration and standardized protocols that the authors say are needed next. For a disease that kills more than 300,000 people a year in China alone, turning initially hopeless diagnoses into curative operations is a goal worth pursuing with both enthusiasm and rigor.

Subject of Research: Physician perceptions and clinical practice of conversion and downstaging therapy for hepatocellular carcinoma in China

Article Title: Physicians’ perceptions of HCC conversion/downstaging therapy: a nationwide survey among tertiary hospital physicians in China

Article References: Bi, X., Liang, X., Tan, G., Zhao, H.-T., Huang, T., Zhao, M., Chen, J., Zhu, X.-D., Xue, J., Sun, H.-C., Cai, J., & China Liver Cancer Study Group Young Investigators(CLEAP) (2026). Physicians’ perceptions of HCC conversion/downstaging therapy: a nationwide survey among tertiary hospital physicians in China. Holistic Integrative Oncology, 5(1), Article 37. https://doi.org/10.1007/s44178-026-00256-x

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00256-x

Keywords: hepatocellular carcinoma, conversion therapy, downstaging, portal vein tumor thrombus, liver cancer, lenvatinib, immunotherapy, TACE, HAIC, surgical resection, China, nationwide survey

Hepatocellular carcinoma, the most common form of primary liver cancer, accounts for nearly 90 percent of liver cancer cases worldwide. Because the disease rarely produces symptoms in its early stages, most patients are diagnosed when the tumor is too advanced for surgical resection, the treatment that offers the greatest survival benefit. Conversion therapy has emerged as a strategy to change that prognosis. By combining locoregional treatments such as transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), clinicians aim to shrink tumors enough to make radical surgery possible. The approach has transformed the treatment landscape, but responses vary dramatically between patients, and predicting who will benefit remains one of the field’s most pressing challenges.

The retrospective study, conducted at the First Affiliated Hospital of Shandong First Medical University, screened 834 patients with primary hepatocellular carcinoma and identified 63 who met the criteria for analysis. Most were male, the majority carried hepatitis B, and more than three quarters had cirrhosis. All received at least two treatment modalities drawn from the conversion therapy arsenal: TACE or HAIC to cut off the tumor’s blood supply and deliver chemotherapy directly, TKIs such as sorafenib or lenvatinib to target tumor signaling pathways, and ICIs such as camrelizumab or sintilimab to unleash anti-tumor immune responses. The results were clinically encouraging. Two patients achieved a complete response and 26 a partial response, yielding an objective response rate of 44.4 percent and a disease control rate of 90.1 percent. Twenty-four patients, or 38.1 percent, were successfully converted to a resectable state, and every one of them underwent radical R0 resection with clear surgical margins.

But the study’s most provocative findings came from the laboratory rather than the clinic. The researchers collected formalin-fixed paraffin-embedded tumor tissue from 15 patients who underwent resection after triple conversion therapy and stratified them by pathological response. Major pathological responders, defined as having more than 50 percent tumor necrosis, formed one group; minor responders, with 50 percent or less necrosis, formed the other. Genomic DNA was extracted and the V3-V4 region of the 16S rRNA gene was amplified and sequenced on an Illumina platform, with amplicon sequence variants clustered using the DADA2 algorithm and taxonomy assigned against the SILVA database. The interval between the last treatment dose and surgery was statistically indistinguishable between the two groups, ruling out differences in treatment withdrawal time as a confounding factor.

The sequencing data revealed a striking divergence. Tumors from minor responders harbored significantly higher microbial alpha diversity, measured across the Chao1, Observed-species, Shannon, and Simpson indices, and their overall community composition differed on principal coordinate analysis of weighted UniFrac distances. At the phylum level, minor responders were enriched in Acidobacteriota, Chloroflexi, Planctomycetota, Gemmatimonadota, and Verrucomicrobiota, while major responders were dominated by Proteobacteria and Bacteroidetes. At the genus level, Halomonas and Arthrobacter stood out in minor responders, whereas Escherichia-Shigella and Limosilactobacillus were markedly more abundant in major responders. Linear Discriminant Analysis Effect Size confirmed these taxa as robust biomarkers, with LDA scores exceeding 3.0.

Functional prediction using PICRUSt2 added a metabolic dimension to the story. Microbiota in minor responders showed enhanced pathways related to methane metabolism, terpenoid backbone biosynthesis, and cofactor and vitamin metabolism, while major responders displayed elevated fatty acid biosynthesis and general functional activity. These metabolic signatures suggest that intratumoral bacteria may influence how tumors process nutrients and metabolites during therapy, potentially modulating the microenvironment in ways that either support or undermine treatment. Escherichia-Shigella, for example, is known to produce short-chain fatty acids with immune-regulatory and anti-tumor properties, while Limosilactobacillus can influence dendritic cell differentiation and thereby shape immune responses.

The most visually compelling evidence came from RNAscope in situ hybridization combined with immunofluorescence staining, which allowed the researchers to see where Halomonas bacteria and CD8-positive T cells actually resided within tumor sections. In major responders, Halomonas signals were sparse while CD8-positive T cells infiltrated the tumor abundantly. In minor responders, the pattern reversed: dense Halomonas colonization coexisted with conspicuously few T cells. The merged fluorescence images revealed a mutually exclusive spatial relationship, with bacteria-rich regions largely devoid of immune cell infiltration. The authors propose that extensive Halomonas colonization may promote immune exclusion, blunting the effectiveness of immune checkpoint inhibitors. One plausible mechanism involves L-arginine, a metabolite essential for T cell activation and proliferation that has been reported to correlate negatively with Halomonas abundance; bacterial consumption of this amino acid could starve T cells of a resource they need to function.

The findings fit into a broader rethinking of tumor biology. Long considered sterile, tumors are now known to harbor microbiota across many cancer types, and these resident microbes can influence everything from tumorigenesis to therapeutic response. Intratumoral Bifidobacterium, for instance, has been shown to stimulate STING signaling in dendritic cells and amplify CD47-based immunotherapy in preclinical models. Prior studies have also linked intratumoral microbial signatures in hepatocellular carcinoma to patient prognosis after surgery. What sets the new work apart is its focus on conversion therapy, an area where intratumoral microbiota had been almost entirely unexplored, and its demonstration that microbial profiles track with pathological response rather than merely with tumor presence.

Notably, the study found no significant differences in microbiota composition between tumor tissue and adjacent non-tumor tissue in patients who underwent direct surgery, nor between direct surgery patients and those who received conversion therapy. The authors attribute this to the small sample size of those comparisons and caution that it limits interpretation. The study also carries other constraints: the cohort was small and relatively homogeneous, the conversion therapy protocols varied between patients, and the retrospective design precludes causal inference. The researchers are now conducting a prospective trial of cardunolizumab and lenvatinib combined with TACE in patients with initially unresectable hepatocellular carcinoma, which may provide the validation needed to move microbial biomarkers toward clinical use.

Even with those caveats, the implications are considerable. If intratumoral microbiota profiles can be measured before or early in treatment, they could help clinicians identify which patients are likely to achieve major pathological response and tailor conversion therapy accordingly. They might also point toward interventions, such as modulating specific bacterial populations or their metabolic products, that could sensitize resistant tumors to immunotherapy. For a disease that remains among the deadliest malignancies worldwide, the idea that answers may lie partly within the tumors themselves, in the microscopic ecosystems that colonize them, represents an intriguing new frontier. The study is the first to demonstrate the involvement of intratumoral microbiota in the response of unresectable hepatocellular carcinoma to conversion therapy, and it provides preliminary but tangible evidence that these microbial communities could serve as prognostic biomarkers for predicting treatment outcomes.

Subject of Research: Intratumoral microbiota composition and its association with pathological response to conversion therapy in unresectable hepatocellular carcinoma

Article Title: Therapeutic response-driven discrepancies in intratumoral microbiota composition of hepatocellular carcinoma following conversion therapy

Article References: Ma, L., Xu, J., Wang, F., Xu, Z., Liu, F., Li, T., Liu, X., Yin, B., Xiao, J., Tian, H., Li, Z., Liu, C., & Liang, J. (2026). Therapeutic response-driven discrepancies in intratumoral microbiota composition of hepatocellular carcinoma following conversion therapy. Holistic Integrative Oncology, 5(1), Article 55. https://doi.org/10.1007/s44178-026-00275-8

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00275-8

Keywords: hepatocellular carcinoma, intratumoral microbiota, conversion therapy, immune checkpoint inhibitors, tyrosine kinase inhibitors, TACE, HAIC, 16S rRNA sequencing, Halomonas, CD8 T cells, pathological response, tumor microenvironment

The study was conducted between September 19 and November 4, 2024, using a stratified random sampling method designed to capture the diversity of Chinese clinical practice. Respondents included 48 surgeons, 48 oncologists, and 24 interventionalists or radiotherapists drawn from tier 1, 2, and 3 cities, including Beijing, Shanghai, Guangzhou, Shenzhen, Wuhan, Chengdu, Xiamen, Fuzhou, and Wuxi. All participating hospitals were ranked secondary A or higher within China’s three-tier hospital classification system and each saw more than 100 patients with biliary tract cancer per year. The physicians averaged 16 years of experience in managing advanced disease, and two-thirds held the title of associate chief physician or above.

The clinical picture that emerged is sobering. Physicians estimated that 58.2 percent of patients with advanced biliary tract cancer are initially deemed to have unresectable tumors, meaning surgery, the only potentially curative option, is off the table from the start. Approximately half of patients present with locally advanced disease, while 44.4 percent have metastatic disease. Most respondents, 85.8 percent, indicated that between 30 and 80 percent of their patients have unresectable or metastatic disease at diagnosis, a figure consistent with the disease’s insidious onset. Because early-stage biliary tract cancer produces few or no symptoms, most patients are diagnosed only after the tumor has progressed beyond the reach of the scalpel.

The survey also documented a shift in the disease’s anatomical distribution. Respondents reported that intrahepatic cholangiocarcinoma, which arises within the liver’s bile ducts, was the most common subtype they encountered, accounting for an estimated 39.2 percent of cases, followed by extrahepatic cholangiocarcinoma at 34.6 percent and gallbladder cancer at 26.2 percent. That ordering differs from epidemiological data collected in China between 2008 and 2012, when gallbladder cancer was the most frequently diagnosed subtype. The authors suggest this shift may reflect changing risk factors, including hepatitis B and C infection, obesity, and diabetes, which have driven a rise in intrahepatic tumors.

On the treatment front, the survey found that physicians estimated 77.3 percent of patients with advanced disease receive first-line therapy, while 22.8 percent receive no antitumor treatment at all. Among those who are treated, immunotherapy combined with chemotherapy was the most commonly used first-line modality, selected by 34.2 percent of physicians, followed by chemotherapy alone at 15.8 percent and local-regional combination therapies at 10.8 percent. Yet guidelines from both China and the National Comprehensive Cancer Network recommend immunotherapy plus chemotherapy as the preferred first-line approach, based on phase 3 trials showing that adding durvalumab or pembrolizumab to gemcitabine and cisplatin improves survival compared with chemotherapy alone. Only about a third of surveyed physicians reported following that standard, exposing a substantial implementation gap.

The specific regimens physicians chose reveal further nuances. Gemcitabine plus cisplatin combined with immunotherapy was the most frequently used immunochemotherapy combination, cited by 52.4 percent of respondents, followed by gemcitabine plus oxaliplatin plus immunotherapy at 31.1 percent. The most commonly paired immunotherapy drugs were durvalumab, sintilimab, tislelizumab, and pembrolizumab. Notably, the survey found relatively high use of sintilimab and tislelizumab despite limited evidence supporting their use in biliary tract cancer, suggesting that real-world practice in China deviates from the evidence base in ways that may reflect drug availability and cost rather than clinical trial data. Targeted therapies, such as FGFR and HER2 inhibitors, remained rare in the first-line setting, used in combination with immunotherapy by only 4.2 percent of physicians.

Geography and economics clearly shape treatment decisions. Physicians in tier 1 and tier 2 cities were significantly more likely than those in tier 3 cities to cite patient baseline status and economic considerations as key factors in choosing an immunochemotherapy regimen, differences the authors attribute to uneven distribution of healthcare resources, hospital capacity, and access to novel therapies. The reasons physicians gave for choosing chemotherapy alone included disease characteristics, patient baseline status, economic considerations, and the evidence level of the regimen. The relatively poor tolerability of gemcitabine plus cisplatin, which is associated with nephrotoxicity, nausea, vomiting, and anorexia, may also explain why some clinicians opt for alternative chemotherapy backbones such as GEMOX.

The picture darkens further after first-line treatment fails. Physicians estimated that only 43.8 percent of patients proceed to subsequent therapy after disease progression, with the overwhelming majority of physicians, 94.2 percent, citing the patient’s inability to tolerate existing regimens as the main barrier. Economic constraints and medications falling outside insurance coverage were cited by 65 percent, and patient transfers to other hospitals by 63.3 percent. Among those who do continue treatment, immunotherapy plus chemotherapy was the most common subsequent modality, followed by chemotherapy alone and immunotherapy plus an anti-angiogenic agent. Existing second-line options offer only modest efficacy, underscoring what the survey’s respondents identified as the field’s most pressing unmet needs: a limited selection of treatment regimens, cited by 46.7 percent, and financial barriers to care, cited by 40 percent.

One of the most intriguing findings concerns conversion and downstaging therapy, an approach in which systemic treatment is used to shrink initially unresectable tumors enough to make surgery possible. Roughly 90 percent of surveyed physicians reported experience with this strategy, and most considered patients with technically resectable intrahepatic metastases, large tumors, or vascular invasion to be suitable candidates. Immunotherapy plus chemotherapy and triplet therapy combining immunotherapy, chemotherapy, and an anti-angiogenic agent were viewed as the most credible conversion regimens. However, most physicians estimated the success rate of conversion therapy at below 40 percent, and the authors caution that phase 3 trials are still needed to validate the efficacy and safety of this increasingly popular approach.

Biomarker testing emerged as another critical bottleneck in the pathway to precision medicine. Although 51.7 percent of physicians expressed high willingness to test patients for actionable gene mutations such as IDH1, HER2, and FGFR2, and for immune-related markers including PD-L1 and tumor mutational burden, only 63.3 percent reported that 20 to 50 percent of their patients were actually tested. High testing cost was cited by 93.3 percent of physicians as the main obstacle, and nearly all noted that the positive detection rate for both immune-related markers and actionable mutations was below 20 percent. Even among patients who tested positive, fewer than half, 41.5 percent, went on to receive biomarker-guided medication, primarily because of economic considerations, poor tolerability, and limited guideline support. Overall physician satisfaction with current treatment and management of advanced biliary tract cancer ranged from 6.1 to 7.5 out of 10, with the lowest scores assigned to overall efficacy and drug accessibility. The authors hope their findings will inform future standardization of care in China, where the incidence and mortality of this challenging cancer continue to rise.

Subject of Research: Treatment patterns and physician decision-making for advanced biliary tract cancer in China

Article Title: Patient Characteristics and Treatment Patterns of Advanced Biliary Tract Cancer (BTC): A Chinese Physician Survey

Article References: Qiu, H., Liu, Q., Wang, Z., Chen, W., Tang, W., & Hao, C. (2026). Patient Characteristics and Treatment Patterns of Advanced Biliary Tract Cancer (BTC): A Chinese Physician Survey. Advances in Therapy. https://doi.org/10.1007/s12325-026-03732-y

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03732-y

Keywords: biliary tract cancer, cholangiocarcinoma, immunotherapy, chemotherapy, China, physician survey, biomarker testing, conversion therapy, gemcitabine, cisplatin, healthcare access, treatment guidelines