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Page 6 of 9 Salleh et al. J Cancer Metastasis Treat 2020;6:31 I http://dx.doi.org/10.20517/2394-4722.2020.70

authors reported that all patients with RECIST-regressive disease exhibited a significant decrease in the
serum levels of CA 19-9 following induction chemotherapy, which indicated a positive correlation between
CA 19-9 levels and RECIST-regressive disease. Importantly, an elevation in the CA 19-9 level was also
[42]
found to be significantly associated with decreased survival .
[43]
Another study conducted by Xu et al. evaluated the efficacy of adjuvant chemoradiotherapy by assessing
the postoperative serum levels of CA 19-9. In this study, adjuvant chemoradiotherapy was found to be
associated with improved surgical outcomes in patients with increased levels of this biomarker, but not in
[43]
patients with the normal levels of CA 19-9 . In addition, a significant improvement in surgical outcomes
was noticed in patients with increased levels of serum CA 19-9 with negative lymph nodes . Overall, these
[43]
findings suggest the importance of evaluating preoperative CA 19-9 levels for monitoring the therapeutic
responses of various regimens, as well as determining the resectability of the disease.

Benefits of serum CA 19-9 levels as a biomarker for determining the surgical resectability in PDAC patients
with jaundice
Santucci et al. performed a study to determine if serum CA 19-9 levels can be exploited as a biomarker
[34]
for predicting the resectability of PDAC, mainly in jaundiced patients. The authors reported that the
mean CA 19-9 level in patients with the resectable disease was significantly lower compared to those with
[34]
locally-advanced or metastatic disease . It has also been observed that the ability of CA 19-9 in precisely
predicting resectability was 0.886 when evaluated with the area under the Receiver Operating Characteristic
(ROC) curve. This implies that the resectability in 88.6% of patients was accurately predicted by the serum
CA 19-9 level. Concurrently, the area under the ROC curve in patients with jaundice corresponded well
[34]
with data obtained for non-jaundiced patients . These findings suggested that CA 19-9 can be explored as
an accurate predictive biomarker to assess the resectability of PDAC patients with jaundice.

[44]
In a separate study, Choi et al. developed an integrated predictive model to determine the long-term
survival in LAPC patients treated with chemoradiotherapy (CRT). The authors reported that pre-CRT
CA 19-9, post-CRT CA 19-9, and a decline in CA 19-9 levels were among the significant factors that
[44]
contributed to the favourable PFS . It has been demonstrated that high-dose radiation, a decline in CA
[44]
19-9 levels, and surgical resection after receiving CRT, were all significantly correlated with longer OS .
Overall, these findings imply the crucial role of CA 19-9 as a biomarker for developing a nomogram to help
determine the patients for CRT, and aiding clinical decision making.

ONGOING CHALLENGES AND LIMITATIONS
There are a number of limitations that can confound the interpretation of CA 19-9 as a biomarker. Despite
its remarkable contribution in clinical practice, the efficacy of CA 19-9 to be exploited as a biomarker
remains controversial as it is not exclusively specific to this disease as numerous benign aetiologies can also
deceptively increase the levels of CA 19-9 [43,45-51] . In addition, this tumour biomarker has been shown to
have a modest and low sensitivity (79%-81%) in symptomatic patients. This also limits its diagnostic utility,
keeping CA 19-9 in the category of those clinical biomarkers whose implications need to be precisely
considered as a screening tool keeping other limitations in place [43,45-51] .

FUTURE PERSPECTIVES
Considering all the discussed limitations, several studies have suggested and evaluated the cut-off levels for
serum CA 19-9 from 37 to 90 U/mL, which resulted in a potentially increased specificity of this biomarker
to 95% [43,44-51] . In other respects, Jahan et al. conducted a study to explore the individual and combined
[52]
Trefoil factors (TFFs) alone and in combination with CA 19-9 as a promising panel for detecting pancreatic
cancer. TFFs are defined as secretory products of cells that produce mucin. The authors reported that a