Potentially practice changing : 68Ga-FAPI-04 PET for Detecting Occult Peritoneal Metastasis in Locally Advanced Gastric Cancer
HIGHLIGHTS:
68Ga-FAPI-04 PET/CT occult pertineal metastasis detection ( OPM ) rate : 15.6%
Senstivity : 75% , Specificity : 94.6%
Due to high specificity, diagnostic laparoscopy can be omitted when 68Ga-FAPI-04 PET/CT negative
Potential to reduce the need for laparoscopic procedures by 84% and preventing 11% of futile gastrectomy
Currently FDG PET has sensitivity of 33% only
Using 68Ga-FAPI-04 PET/CT could prevent 1 in 6 unnecessary gastrectomies
10 KEY TAKE AWAY POINTS :
- 68Ga-FAPI-04
PET/CT detects occult peritoneal metastasis (OPM) in about 16% of patients
with locally advanced gastric cancer, upstaging them to stage IV and
averting futile curative surgery.jnm.snmjournals
- Diagnostic
performance for OPM is strong: sensitivity 75%, specificity 94.6%, overall
accuracy 91.7%, with an AUC of 0.83 against laparoscopic staging plus
peritoneal cytology as the reference standard.jnm.snmjournals
- Using
68Ga-FAPI-04 PET/CT instead of routine staging laparoscopy yields an
estimated cost saving of roughly $980 per patient in this cohort.jnm.snmjournals
- Combining
FAPI PET/CT with selective laparoscopy can reduce the number of
laparoscopic procedures by about 84% while still preventing roughly 11% of
futile gastrectomies, with a small net cost saving.jnm.snmjournals
- FAPI
PET/CT improves preoperative OPM detection compared with CT-based staging
alone and has the potential to meaningfully change treatment intent from
curative to palliative in a notable minority of patients.ascopubs+1
- The
study is a single‑centre prospective cohort with 109 patients, which is
methodologically robust for diagnostic accuracy but limits
generalisability to other centres and healthcare systems.bmjopen.bmj+1
- Existing
systematic reviews show FAPI tracers generally outperform FDG in gastric
cancer for detecting primary tumours and metastases, supporting the
biological plausibility of the high accuracy seen in this cohort.frontiersin+1
- Current
standard staging (CT ± FDG PET/CT plus staging laparoscopy) misses a
proportion of peritoneal disease and relies on an invasive procedure that
carries morbidity and resource burden.pmc.ncbi.nlm.nih+1
- For
the UK NHS, 68Ga-FAPI-04 PET/CT is not yet routine; potential adoption
would require access to FAPI radiotracers, specialised PET infrastructure,
training, and health‑technology assessment for commissioning.pmc.ncbi.nlm.nih+1
- In
practice, FAPI PET/CT is most likely to be introduced first in tertiary
centres for locally advanced gastric cancer as a pre‑laparoscopy staging
tool, with further multicentre validation needed before broad guideline
changes (e.g. NICE) are realistic.pmc.ncbi.nlm.nih+1
High-Impact Oncology Article: Critical Appraisal
Article Title: 68Ga-FAPI-04 PET for Detecting Occult
Peritoneal Metastasis in Locally Advanced Gastric Cancer: Diagnostic
Performance and Cost Analyses in a Single-Center, Prospective Cohort Study
Authors: Not specified in available abstract
Journal: Journal of Nuclear Medicine
Publication Date: December 3, 2025
DOI: 10.2967/jnumed.125.270633
Study Design and Methodology: Strengths and Limitations
Strengths:
The study employed a prospective, single-center cohort
design—the methodological gold standard for diagnostic accuracy research. The
use of laparoscopic staging combined with peritoneal washing cytology as a
reference standard represents appropriate validation methodology, as these
techniques remain the current gold standard for detecting occult peritoneal
metastasis (OPM) in locally advanced gastric cancer. The study addressed a
critical clinical gap by evaluating a novel PET tracer (68Ga-FAPI-04) against current
diagnostic practice, which is essential for validating new imaging modalities.
The inclusion of diagnostic cost analysis alongside
diagnostic accuracy strengthens the practical applicability of findings,
providing healthcare systems with economic impact data necessary for
implementation decisions. The cohort size of 109 patients provides adequate
statistical power for estimating sensitivity, specificity, and diagnostic
accuracy, with appropriate confidence intervals reported (95% CI: 0.72-0.94).
Limitations:
As a single-center study, the findings may not be
generalizable to other institutions with different imaging protocols, patient
populations, or operator expertise. The study enrolled patients between
November 2022 and August 2024 with publication in December 2025, creating a
potential publication lag that may affect contemporaneity of practices.
Single-center designs are prone to selection bias, particularly given that
specialized nuclear medicine centers performing FAPI PET imaging may differ
systematically from community hospitals in patient management practices.
The study lacks stratification by important prognostic
variables such as histological subtypes (intestinal vs. diffuse), Lauren
classification, or molecular subtypes (MSI-H, EBV-positive), which affect
gastric cancer biology and imaging characteristics. No data on interobserver or
intraobserver variability in PET image interpretation are provided, limiting
assessment of operational implementation reliability. The study does not
directly compare FAPI-04 PET to FDG-PET/CT or other competing imaging modalities
within the same patient cohort, relying instead on historical comparison with
published literature.
Patient Population and Generalizability
Population Characteristics:
The study enrolled patients with histologically confirmed
locally advanced gastric or gastroesophageal junction adenocarcinoma. With 109
patients accrued over 21 months (November 2022–August 2024), the enrollment
rate of approximately 5 patients per month reflects a moderate-sized,
specialized nuclear medicine center. The preliminary report from ASCO 2024
(based on 49 patients) suggests a predominantly male cohort (consistent with
gastric cancer epidemiology), though full demographic details were not available
in the publication summary.link.springer
Generalizability Concerns:
The single-center setting limits generalizability. Tertiary
nuclear medicine centers with expertise in FAPI PET imaging may represent the
upper end of the performance spectrum, potentially overestimating diagnostic
accuracy achievable in routine practice. No information on socioeconomic
factors, comorbidity burden (ASA classification), or fitness for surgery was
provided, limiting assessment of applicability to unselected populations.
The study inclusion criteria were not fully detailed in
available abstracts, but restriction to "locally advanced" disease
(presumably cT3-4 and/or cN+, M0 on CT) means findings may not apply to
early-stage or metastatic presentations. Given that the study was conducted in
a single center (location not specified in available summary), results may
reflect institutional practice patterns and expertise not universally available
across healthcare systems.
Key Findings and Statistical Significance
Primary Endpoint Results:
The study reported that 68Ga-FAPI-04 PET/CT identified
occult peritoneal metastasis in 17 of 109 patients (15.6%), resulting in
upstaging from stage III to stage IV in 15.6% of the cohort. This proportion
aligns closely with the 18.4% OPM detection rate from the earlier ASCO 2024
presentation (9 of 49 patients), indicating consistency across the expanded
patient cohort.
Diagnostic Accuracy Metrics:
- Sensitivity:
75.0% (95% CI not fully specified, but AUC 0.83)
- Specificity:
94.6%
- Diagnostic
Accuracy: 91.7%
- Area
Under the Curve (AUC): 0.83 (95% CI: 0.72-0.94)
These metrics demonstrate clinically meaningful performance.
The sensitivity of 75% indicates that three-quarters of patients with true
occult peritoneal metastasis would be correctly identified preoperatively,
potentially avoiding futile gastrectomy. The specificity of 94.6% suggests that
positive findings would rarely represent false positives, reducing the risk of
inappropriate treatment de-escalation.
Cost Analysis Results:
The study demonstrated net cost savings of $979.30 per
patient when FAPI-04 PET/CT was used as a standalone staging modality compared
with laparoscopic staging alone. When FAPI-04 PET/CT was combined with
laparoscopic staging, there was a minimal cost savings of $232.30 per patient,
while reducing the need for laparoscopic procedures by 84% and preventing 11%
of futile gastrectomies. These findings suggest that FAPI-04 PET/CT could serve
as a cost-effective alternative for initial OPM screening prior to laparoscopy,
potentially reducing the invasiveness of the diagnostic pathway.
Statistical Significance:
The 95% confidence intervals provided for the AUC
(0.72-0.94) do not cross the null value of 0.50, indicating statistically
significant diagnostic performance. However, the relatively wide confidence
interval reflects moderate sample size for subgroup analysis and possible
heterogeneity in OPM presentation.
Clinical Relevance and Practice-Changing Potential
Addressing Current Clinical Need:
Occult peritoneal metastasis represents the most common form
of distant metastasis in gastric cancer, with prevalence ranging from 10-20% in
locally advanced disease. Current standard staging approaches (CT + staging
laparoscopy) detect approximately 19% of patients with peritoneal disease
and/or locally nonresectable tumors requiring conversion from curative to
palliative intent. The high false-negative rate of CT imaging for peritoneal
disease (66-87% missed detection in some series) creates a critical clinical
gap that leads to unnecessary laparotomies and associated morbidity.onlinelibrary.wiley
By improving preoperative OPM detection, FAPI-04 PET/CT has
potential to reduce the proportion of patients undergoing futile major surgery.
The 15.6% upstaging rate translates to preventing approximately 1 in 6
unnecessary gastrectomies in locally advanced disease, substantially reducing
patient morbidity from major surgery when palliative chemotherapy would be more
appropriate.
Comparison to Systemic Reviews:
Recent meta-analyses demonstrate that 68Ga-FAPI PET/CT
achieves superior diagnostic performance compared to conventional 18F-FDG
PET/CT in gastric cancer. Systematic reviews report FAPI sensitivity of 0.84
(95% CI 0.67-0.94) versus FDG sensitivity of 0.46 (95% CI 0.32-0.60) for
gastric cancer staging, with particular superiority in detecting peritoneal
metastases. The current study's sensitivity of 75% for occult peritoneal
metastasis (using FAPI-04 specific to this finding, rather than overall tumor
detection) is consistent with this literature base.ascopubs+1
Potential for Practice Change:
The diagnostic superiority of FAPI-04 PET/CT, combined with
cost-effectiveness, creates a compelling case for protocol modification. The
84% reduction in required laparoscopic procedures would substantially decrease
procedural-related complications (reported at 0.8% requiring reintervention in
the original PLASTIC trial), reducing perioperative morbidity. For patients
with limited life expectancy due to stage IV disease, avoiding laparoscopy
accelerates treatment planning and initiation of palliative therapy.onlinelibrary.wiley
Comparison to Current Standard of Care
Current UK/European Standard Practice:
According to the 2021 PLASTIC trial (the largest prospective
European study of gastric cancer staging), current best practice for locally
advanced gastric cancer involves:onlinelibrary.wiley
- Computed
tomography (chest, abdomen, pelvis with arterial and portal venous
phases)
- Staging
laparoscopy with peritoneal cytology (detects peritoneal/locally
nonresectable disease in ~19% of locally advanced cases)
- FDG-PET/CT
(limited sensitivity of 33% for distant metastases, low positive
predictive value in mucinous/signet ring histology)
The PLASTIC trial concluded that staging laparoscopy adds
considerable value but questioned the utility of FDG-PET/CT for routine
staging, noting limited additional value beyond CT and laparoscopy.onlinelibrary.wiley
Advantages of FAPI-04 PET/CT Over Current Standard:
The key clinical advantage over FDG-PET/CT is superior
sensitivity for peritoneal metastases. Unlike FDG-PET/CT (which targets glucose
metabolism and performs poorly in gastric cancers with low 18F-uptake), FAPI-04
targets fibroblast activation protein (FAP) expressed on cancer-associated
fibroblasts (CAFs) in the tumor stroma. This mechanistic difference explains
superior performance in:
- Diffuse/signet
ring histology: Historically, FDG-PET shows minimal uptake in
diffuse-type gastric cancers due to low glucose metabolism. FAPI-04 is not
limited by histological subtype.
- Peritoneal
carcinomatosis: Early peritoneal deposits (microscopic to small
macroscopic) may not demonstrate FDG avidity but show FAP expression
through stromal involvement.
- Overall
sensitivity for metastases: FAPI pooled sensitivity of 0.84 vs. FDG
sensitivity of 0.46 represents an 82% relative improvement in detection.
Potential Disadvantages/Considerations:
FAPI-04 PET/CT is not yet widely available in routine NHS
practice. Clinical implementation would require:
- Infrastructure
investment: Dedicated or shared cyclotron facilities for 68Ga
production, which remain limited in UK NHS centers
- Staffing:
Nuclear medicine physicians and radiologists trained in FAPI PET image
interpretation
- Regulatory
approval: While not yet formally restricted, 68Ga-FAPI
radiopharmaceuticals require regulatory framework establishment for
routine clinical use in UK NHS
The specificity of 94.6% in the study, while high, is not
superior to laparoscopic staging (which has near-100% specificity when abnormal
findings are biopsied). Therefore, FAPI-04 PET/CT would be most valuable as a
first-line screening tool to reduce unnecessary laparoscopies in truly
OPM-negative patients.
Implications for UK NHS Practice
Current Context:
Approximately 6,000-7,000 new cases of gastric cancer are
diagnosed annually in the UK, with about 40-50% presenting as locally advanced
disease (cT3-4 and/or cN+). Of these 2,400-3,500 patients with locally advanced
disease annually, approximately 15-20% (360-700 patients) have occult
peritoneal metastasis missed by initial CT staging. Current practice mandates
diagnostic laparoscopy for these patients, representing a substantial burden of
invasive procedures with ~0.8-1% morbidity requiring intervention.
Implementation Challenges:
- Availability
Gap: As of 2025, FAPI PET imaging remains concentrated in academic
centers and is not available in most NHS cancer centers. The UK has
approximately 30-40 PET centers, but only a fraction have FAPI capability.
- Regulatory
and Commissioning Status: FAPI radiopharmaceuticals lack formal NICE
guidance as of the publication date. Implementation would require health
technology assessment and formal commissioning through NHS England
Specialist Commissioning.
- Workforce
Development: Current nuclear medicine and radiotherapy workforce in
the UK would require training in FAPI PET interpretation. Most practicing
nuclear medicine physicians have minimal experience with FAPI tracers.
- Cost
Considerations: Preliminary cost analysis suggests £900-£1,000 per
FAPI-04 PET/CT examination. While achieving marginal cost savings when
compared with laparoscopy alone, actual implementation cost would include
capital equipment investment and cyclotron infrastructure.
Clinical Practice Recommendations:
Based on this study and supporting evidence, FAPI-04 PET/CT
would be most appropriately implemented as:
- Primary
staging modality in selected centers: For patients with locally
advanced gastric cancer deemed fit for curative surgery, FAPI-04 PET/CT
could replace laparoscopy as the initial staging investigation, using
laparoscopy selectively only for FAPI-PET/CT-positive findings or in
FAPI-equivocal cases.
- Rescue
imaging in high-risk cases: For patients with signet ring cell
carcinoma or diffuse-type gastric cancer where FDG-PET/CT is known to have
poor performance, FAPI-04 PET/CT could identify patients with occult
metastases before attempting curative surgery.
- Integration
into multidisciplinary decision-making: Results would need to be
incorporated into structured cancer center MDT discussions, with clear
protocols for management of FAPI-positive findings (conversion to
palliative pathway) versus FAPI-negative findings (proceeding to
laparoscopy or surgery).
Service Development Pathway:
For NHS England implementation, a phased approach would be
optimal:
- Phase
1 (2025-2026): Establish FAPI PET capability in 2-3 tertiary cancer
centers with existing cyclotron/PET facilities (e.g., large academic
centers)
- Phase
2 (2026-2027): Conduct pragmatic randomized controlled trial comparing
FAPI-04 PET/CT + laparoscopy vs. standard CT + laparoscopy for locally
advanced gastric cancer
- Phase
3 (2027+): Subject to trial results, develop NICE guidance and
commission selective expansion to network of 8-12 regional cancer centers
Limitations and Outstanding Questions
- Lack
of Prospective Comparative Design: The study does not include
head-to-head comparison with FDG-PET/CT within the same patient cohort,
limiting ability to directly assess incremental value.
- Single-Center
Design: Reproducibility in other centers with different protocols and
expertise remains unconfirmed. A multicenter validation study (analogous
to the PLASTIC trial for FDG-PET/CT staging) would strengthen the evidence
base.
- Incomplete
Patient Stratification: The study lacks detailed analysis by
histological subtype, molecular classification (EBV-positive vs.
genomically stable vs. chromosomal instability), and treatment received
postoperatively, limiting ability to identify highest-benefit subgroups.
- No
Data on Impact on Survival: The study focuses on diagnostic accuracy
and treatment strategy change but does not report whether FAPI-04
PET/CT-guided treatment modification improves overall survival,
recurrence-free survival, or quality of life—critical outcomes for
treatment decision-making.
- Limited
Data on Prognostic Value: Whether FAPI-04 uptake parameters (SUVmax,
SUVmean, tumor-to-background ratio) provide independent prognostic
information beyond staging remains unexplored.
Conclusion
The 68Ga-FAPI-04 PET/CT study represents a significant
advance in preoperative staging of locally advanced gastric cancer, with the
potential to reduce unnecessary surgery in approximately 15-16% of patients
with occult peritoneal metastasis. The diagnostic accuracy metrics (sensitivity
75%, specificity 94.6%, AUC 0.83) substantially exceed those of FDG-PET/CT and
complement laparoscopic staging by reducing the proportion of invasive
procedures required.
For UK NHS implementation, this study provides compelling
clinical and economic justification for establishing FAPI PET capability at
selected tertiary cancer centers. However, current practice should continue
with standard diagnostic approaches (CT + staging laparoscopy) until: (1)
multicenter prospective validation is completed, (2) regulatory and
commissioning pathways are established, and (3) organizational capacity for
FAPI imaging infrastructure is developed.
The study demonstrates that FAPI PET/CT has
practice-changing potential in gastric cancer staging, shifting the evidence
base toward imaging modalities that better reflect tumor biology (CAF stromal
interactions) rather than metabolic activity alone. Implementation would
require coordinated health service development and clinician education but
could meaningfully reduce perioperative morbidity while maintaining therapeutic
efficacy for curative-intent treatment.
References
68Ga-FAPI-04 PET for Detecting Occult Peritoneal Metastasis
in Locally Advanced Gastric Cancer: Diagnostic Performance and Cost Analyses in
a Single-Center, Prospective Cohort Study. Journal of Nuclear Medicine. 2025
Dec 3. DOI: 10.2967/jnumed.125.270633ascopubs
ASCO 2024 Presentation. 68Ga-FAPI-04 positron emission
tomography/computed tomography (PET/CT) for detecting occult peritoneal
metastasis in locally advanced gastric cancer: A single-center prospective
cohort study. J Clin Oncol. 2024 May 31;42(16 Suppl):4081.link.springer
18F-Fludeoxyglucose-Positron Emission Tomography/Computed
Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A
Multicenter Prospective Dutch Cohort Study (PLASTIC). JAMA Surg.
2021;156(10):928-936.onlinelibrary.wiley
Evaluation of FAPI PET imaging in gastric cancer: a
systematic review and meta-analysis. Theranostics. 2023;13(12):4694-4710.ascopubs
Head-to-head comparison of 68Ga-FAPI-04 PET/CT and 18F-FDG
PET/CT in the evaluation of primary digestive system cancer: a systematic
review and meta-analysis. Front Oncol. 2023;13:1202505.link.springer
