Review Article

J Surg Oncol. 2021

Neoadjuvant therapy for pancreas cancer:

Global perspectives and optimal care
pathways in low to middle-income
countries
Introduction
- Ever-increasing incidence of
cancer worldwide
- population growth
- ageing
- increased prevalence of cancer
risk factors
- socioeconomic factors
incidence (14th) x mortality (8th)
- The high mortality, with a
dismal overall 5‐year
survival rate of about 7%
- without much difference
between high‐income
countries (HICs) and LMICs
- is a reflection of the little
progress achieved with
screening and management
of early as well as advanced
pancreatic cancer
Epidemiology
● The age‐standardized incidence
rates for pancreatic cancer on an
average are of

- 7.3 and 1.7/100,000 amongst

males,
- 5.1 and 1.4/ 100,000 amongst
females in HICs and LMICs,
respectively

● More than 50% of patients harbor

metastatic disease at initial
presentation
Epidemiology
- Apparent variations in incidence
between HICs and LMICs
- scarcity of efficient diagnostic tools in LMICs
- potential exposure to known or suspected
lifestyle and environmental risk factors
related to pancreatic cancer
- scarcity of efficient cancer data registry
practices in LMICs
- undermining the concern about the growing
burden of pancreatic cancer in LMICs
Prognosis
- However, in patients with resectable
disease
- which constitutes less than 25% of all
patients
- the overall prognosis is better with a 5‐
year survival of nearly 22% when
subjected to successful R0 resection
- With improvements in patient
selection, supportive care and
systemic therapy, there has been a
slow but steady improvement in
survival for early pancreatic cancer
IN‐CLINIC PRACTICES AT OUR TERTIARY CARE CANCER
CENTER

- (CECT) of the abdomen and pelvis, or a magnetic

resonance imaging (MRI)
- Assessing resectability
- only about 15%–20% of the patients are eligible for upfront surgery
- Endoscopic‐retrograde‐cholangiopancreatography (ERCP)
- Cancer‐antigen 19‐9
- Biopsy confirmation
- is not considered essential in patients with resectable pancreatic cancer
that are scheduled for upfront surgery but is mandatory in those who are
candidates for neoadjuvant and palliative systemic therapies
- Endoscopic‐ultrasound (EUS)
REVIEW OF MULTIMODALITY PRACTICES FOR EARLY OR LOCALIZED PANCREATIC CANCER

- Review of evidence for adjuvant therapy in resected pancreatic cancer

- Several prospective clinical trials have demonstrated a survival benefit of adjuvant
chemotherapy
- Patients who are fit with a good performance status should receive combination chemotherapy regimen such as
FOLFIRINOX (Folinic acid, 5Flourouracil [5FU], Irinotecan and Oxaliplatin)
- For patients with borderline performance status and comorbidities, gemcitabine alone or gemcitabine plus
capecitabine (Gem‐Cape) can be a reasonable option
- The benefit of adjuvant radiotherapy is, however, less certain and practice is widely variable
in our country driven by institutional consensus
 The multicenter PRODIGE‐
24 trial established superiority
of FOLFIRINOX in terms of
both disease free survival
(DFS) (21.6 vs. 12.8 months;
hazard ratio [HR]: 0.58; 95%
confidence interval [CI]: 0.46–
0.73) and overall survival
(OS) (54 vs. 35 months; HR:
0.64; 95% CI: 0.48–0.86) in
comparison to monotherapy
with gemcitabine
- Delivery of FOLFIRINOX can be
challenging in LMIC for various
reasons
- nutritional status of patients
- postoperative recovery from surgery
and complications
- performance status
- need for frequent hospital visits
- central venous access
- toxicities
- need for more supportive care and
cost of therapy
Rationale for neoadjuvant therapy in resectable and borderline resectable pancreatic cancer

- The futility of surgical misadventure

(inability to secure a R0 resection)
- Reduce positive margins
- Down staging of nodal disease
- Neoadjuvant approach can mitigate
issues as
- Prolonged postoperative recovery and
persistently poor performance status can
result in delayed initiation of adjuvant
chemotherapy, lower doses being
delivered and in many instances, failure
to receive any adjuvant therapy.
Rationale for neoadjuvant therapy in resectable and borderline resectable pancreatic cancer

- Early treatment of micrometastases

may lead to lower incidence of
systemic failures
- Neoadjuvant therapy helps select
patients with favorable disease
biology for aggressive resections

x
. The rate of R0 resection was higher in the neoadjuvant group (72% vs. 40%; p = .001) with a
survival benefit associated with R0 resection (HR: 0.47) when compared to non ‐R0 resection
CHALLENGES IN THE DELIVERY OF OPTIMAL NEOADJUVANT CARE IN LMICs

● Majority of cancer centres in LMICs lack a EUS biopsy facility and the infrastructure and/or expertise for
radiological evaluation.
● Pancreatic surgery (especially pancreatico‐duodenectomy [PD] or Whipple's procedure) is a demanding
procedure.
● Optimal results require
○ adequate preoperative evaluation,

○ proper patient selection and optimisation

○ standardised perioperative protocols and most importantly,

○ an experienced multidisciplinary team to deliver care.

● However in LMICs, there are few centres of excellence that have the experience and expertise to
manage large volumes of patients with pancreatic cancer
Thank you !