Page 87 - Read Online

Page 16 of 26 Skorupan et al. J Cancer Metastasis Treat 2023;9:5 https://dx.doi.org/10.20517/2394-4722.2022.106

Recurrence following surgery is estimated to be > 50%, especially in patients with Stage II or III disease;
however, it remains unclear whether addition of adjuvant therapy is of benefit to PACC patients. Patients
receiving adjuvant therapy had better OS than those that did not in one large retrospective population-
[142]
based study . Others found that the benefit was only associated with administration of platinum-based
chemotherapy or presence of node-positive disease [166,168] . A fourth study found no survival benefit for
[141]
[143]
patients who received adjuvant chemotherapy compared to those who did not . Choice of chemotherapy
regimen may prove a confounder in the latter study; single-agent gemcitabine was the chemotherapy
regimen administered to 60% of patients in that study, and as discussed below, the benefit of gemcitabine in
PACC appears to be limited. Another smaller study of 9 patients found that patients receiving 5-FU-based
adjuvant chemotherapy had superior overall survival to those receiving a gemcitabine-based regimen . A
[169]
randomized study of adjuvant therapy in PACC could resolve this question but is unlikely to be feasible
given the rarity of the tumor.

Neoadjuvant therapy has not been thoroughly explored in this disease. One case study reported on a 65-
year-old PACC patient who had a complete pathologic response to neoadjuvant modified FOLFIRINOX
and remained in remission at 33 months post-resection without adjuvant treatment. It is anticipated that
more resectable PACC patients may receive neoadjuvant therapy, given the trend towards this paradigm in
PDAC.

Recurrent disease following resection
Re-resection at the time of recurrence has been performed in selected cases of PACC with some
success [170,171] . One case report identified a patient with recurrent disease who appeared to be cured after
treatment with radiofrequency ablation (RFA) and combination chemotherapy and a second who
experienced a long remission after RFA . These case reports suggest that local therapy may still be
[172]
curative in some cases of post-surgical recurrence.

Advanced disease
In metastatic or locally advanced PACC multiple therapeutic modalities have been used. Unlike in PDAC,
metastasectomy is sometimes performed in conjunction with resection of the primary tumor. One single
institution case series of 64 PACC patients found that patients with distant metastases who received surgery
had no difference in overall survival compared to those who did not , but it is unclear how many received
[141]
surgery with curative intent versus a palliative procedure. Multiple case reports describe metastasectomy
being beneficial in individual patients. Sumiyoshi et al. reported ongoing recurrence-free survival at 73
months for one patient following resection of the primary tumor in combination with removal of several
synchronous peritoneal nodules followed by continuous S-1 chemotherapy . Another case study
[173]
described a patient who had multiple metastasectomies between sequential lines of combination
chemotherapy that has survived over 10 years since initial diagnosis . A third case report outlined the
[174]
course of a metastatic patient who received neoadjuvant capecitabine/oxaliplatin followed by resection of
the primary tumor with hepatectomy resulting in over 30 months of disease-free survival before recurrence.
The patient subsequently restarted chemotherapy and remained in complete response for the last 3
years . These inspiring cases suggest that outcomes of metastasectomy in PACC may more closely
[175]
resemble those of colon cancer patients than PDAC patients and that surgical intervention could be of
benefit to patients with oligometastatic disease in selected cases. Further study of this treatment paradigm is
needed.

For patients with locally advanced disease, upfront FOLFIRINOX chemotherapy can be successful enough
at debulking to allow resection . Descriptions of successful debulking with other regimens have not been
[176]