The median disease-free survival following complete resection of pancreatic cancer and adjuvant chemotherapy with gemcitabine was reported as 13.4 months and 6.9 months for untreated patients.[
3,
18] The CONKO-001 trial demonstrated a longer disease-free survival with adjuvant chemotherapy in R0- and R1-resected patients,[
3] and other studies confirmed the benefit of adjuvant chemotherapy.[
10,
19,
20] We identified initial lymph node involvement and tumor grade as risk factors for early tumor recurrence, but not the resection status R0
vs R1. In general, overall survival remains poor due to tumor recurrence in almost all patients. European Society for Medical Oncology guidelines[
21] as well as the national German Society for Digestive and Metabolic Diseases guidelines[
11] lack any recommendation for systematic follow-up of patients during adjuvant therapy. Likewise, National Comprehensive Cancer Network (NCCN) guidelines suggest baseline CT scan before adjuvant treatment, but no imaging during chemotherapy.[
22] This may be due to the lack of data evaluating the onset of tumor recurrence during adjuvant chemotherapy. In our population, 37% (13/35) patients had an early tumor recurrence during adjuvant chemotherapy that resulted in a significant shorter overall survival of 9.3 months as compared with 26.3 months in patients without early recurrence. Only very limited data are available on early tumor recurrence during adjuvant treatment, because existing trials on adjuvant therapy examined only general, clinical evident tumor recurrence, and did not analyze the onset of tumor recurrence during adjuvant chemotherapy.[
3,
4,
12,
18] Recently, it was shown that postoperative Ca-19 levels, which were not routinely determined in our study, have a discriminatory value.[
23] In the postoperative setting the authors stated that patients with a postoperative CA 19-9 level >180 U/mL have a worse survival than those with CA 19-9 lower than 180 U/mL. These patients should be considered for other therapeutic strategies.
Given the significantly longer overall survival of patients without early pancreatic cancer recurrence in our population, detection of early recurrence has important prognostic consequences. In addition, the therapeutic algorithm will change when patients develop metastasis or tumor recurrence during adjuvant therapy.[
11,
21,
24] Tumor recurrence during adjuvant treatment with gemcitabine, 5-fluorouracil or chemoradiation demonstrates a lack of efficacy of the regimen used. Chemoradiation, second-line chemotherapy[
16,
17] or intensification of therapy, eg, combination therapies with gemcitabine/erlotinib, gemcitabine/capecitabine, or 5-FU/irinotecan/oxaliplatin[
13,
14,
25,
26] are able to prolong survival in selected patients, even though a survival benefit of an intensified survival strategy has not been demonstrated in randomized trials so far. On the other hand, patients with a poor performance status may be best served by best supportive care without any systemic treatment.[
15,
26] Identification of patients with early recurrence of pancreatic cancer is therefore an important issue, as regular staging of the tumor during chemotherapeutic treatment, eg, using CT scans, allows the selection of an appropriate regimen and avoids unnecessary cytotoxic treatment. Clinical practice guidelines should therefore include a recommendation for regular staging of patients during adjuvant treatment. Because the median time to early tumor recurrence was only 3.6 months in our study, we propose an initial postoperative CT scan, followed by regular staging every 2–3 months as recommended in the palliative setting[
21] and by the current NCCN guidelines.
We identified initial lymph node involvement and tumor grade as risk factors for early tumor recurrence, but not the resection status R0
vs R1, even though R1 resection is known to be an important risk factor for overall survival.[
12,
21] In the near future there may be important molecular prognostic factors for the selection of appropriate chemotherapy regimens (eg, MMP7, RRM1, ERCC1), which will lead to better identification of patients for treatment than CT follow-up screening.[
27–
29]
In summary, especially patients with lymph node metastasis should receive regular response evaluation during adjuvant chemotherapy. At present, not only the patients with lymph node metastasis should receive regular response evaluation but all of the patients should have a baseline CT before any adjuvant treatment. These findings point to a potential benefit for patients undergoing resection of pancreatic cancer, even in those with extensive disease.
