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Page 10 of 26 Skorupan et al. J Cancer Metastasis Treat 2023;9:5 https://dx.doi.org/10.20517/2394-4722.2022.106

The PDAC serum tumor marker Carbohydrate Antigen 19-9 (CA 19-9) is frequently expressed in ASCP
[45]
and can be used as surrogate marker of tumor response similar to PDAC . CEA elevation can also be seen.
Clinical management of ASCP
There are currently no treatment guidelines for ASCP. All treatment is extrapolated from standards of care
for PDAC as no prospective or randomized trials examining treatment paradigms have been reported.
Staging of ASCP is as per PDAC staging [Table 1].

Resectable disease
Resection is recommended for patients with early-stage disease and several population-based studies have
demonstrated a significant survival advantage for patients with locoregional disease who undergo surgery
versus those who do not [79-81] . R1 resection was associated with worse outcomes in one smaller single-
institution study that included only one patient with this resection status , but no contribution of R0 status
[50]
to survival was found in two larger population-based studies [78,80] . A separate retrospective single-institution
study found that a positive resection margin was negatively associated with survival . Unfortunately,
[101]
margin positive rates exceeded 20% in one study examining ASCP cases in the National Cancer Database
[49]
and another large surgical case series . Although better tumor removal during surgery appears
advantageous to patients, the risks of surgery remain significant. The post-operative mortality rate at 90
days reached 6.5% for ASCP patients in one population-based study. Higher mortality was associated with
more advanced age and increasing co-morbidities . Surgery is an important part of treatment for patients
[102]
with resectable disease.

Addition of chemotherapy before or after surgery appears to be beneficial. Recent retrospective population-
based studies have shown improved survival outcomes in patients who receive adjuvant chemotherapy, with
a > 50% decrease in mortality as compared to surgery alone. However, patients receiving multi-modal
therapy were more likely to be younger and to have fewer co-morbidities than those who did not receive
post-operative chemotherapy, confounding survival assessments [80,102] . Nevertheless, chemotherapy does
appear active in ASCP patients: patients with resectable disease who received chemotherapy alone had
[102]
similar median OS as those who received surgery alone, suggesting it has a similar magnitude of benefit .
In a separate, but smaller, single institution, retrospective case series where the populations receiving or not
receiving adjuvant therapy were similar, receipt of adjuvant therapy was still strongly associated with
improved survival. Backbones of the administered regimens were either fluoropyrimidine or gemcitabine;
however, only inclusion of a platinum chemotherapy (cisplatin or oxaliplatin) improved survival in this
[101]
population . Notably, delivery of chemotherapy in the neoadjuvant versus adjuvant setting did not
influence overall survival . This is difficult to understand, given that at least 50% of pancreatic cancer
[102]
patients are unable to complete their planned adjuvant therapy [102-104] . The optimal timing and absolute
benefit of chemotherapy in resectable ASCP patients are still unclear.

Radiotherapy
Radiation monotherapy is associated with poor survival. Amongst all treatment modalities, using
radiotherapy alone to treat ASCP patients resulted in the shortest median survival, estimated at just 2.3
months . The relative insensitivity of ASCP to radiation therapy is somewhat surprising given that true
[102]
squamous cell cancers are well known to have a higher sensitivity to radiation than adenocarcinoma and
radiation can be used as definitive treatment in some clinical circumstances [105-108] . Although the population
offered radiation alone may have been less fit than those offered other modalities confounding an accurate
assessment of the absolute benefit of radiation, it is still clear that radiation will not serve as a potentially
curative treatment in ASCP. Even so, neoadjuvant chemoradiation was associated with improved survival as