8th AJCC stage demonstrates a more equal distribution among stages and increases prognostic accuracy compared with 7th AJCC stage. In an international multicenter cohort study including 1525 consecutive patients, the new T stage does not demonstrate significant correlation with survival on univariate or multivariate analysis, whereas the new N stage showed accurate discrimination of survival . These results were consistent with our current study. However, the superiority of the 8th edition in evaluating the relationship between tumor location and clinical characters has not been investigated in PC patients, to our knowledge. Based on the new 8th AJCC stage, we found new diversity between ph and pbt cancers from a multicenter cohort study.
In anatomy, cell composition, blood supply, lymphatic and venous backﬂow, and innervations are significantly different between ph and pbt cancers . In clinic, tumors at different locations (ph vs pbt) display different clinical presentation, treatment efficiency (surgery and chemoradiotherapy) and prognosis . The incidence rate for ph cancer has remained at 5.6% per 100,000, whereas the rate for pbt cancers has increased by 46% between 1973 and 2002 in the SEER database . Though both ph and pbt cancers had a higher proportion diagnosis in the distant stages (a neoplasm that has spread to parts of the body remotes from the primary tumor or to distant lymph nodes), patients with ph cancer were more likely to have localized and regional diseases (12.9% and 32.2%, respectively) as compared with pbt cancers (6.6% and 13.9%, respectively) . According to 7th AJCC stage, there was no significant difference in TNM stage between resected ph and pbt cancers . However, in current study, we find new clinical difference between curatively resected ph and pbt cancers bases on 8th AJCC stage, which hasn’t been reported previously to our knowledge.
The alteration of the definitions of T and N is the main changes in 8th AJCC stage compared with the 7th AJCC stage . Just shown in supplemental Table 1 and 2, extra-pancreatic invasion can be difficult to predict accurately before surgery and may be inconsistently assessed by pathologists . T3 tumors are now defined as those ≥4 cm, while nodal involvement has been improved from a binary system to one based on extent of nodal involvement. In current study, increasing tumor size and advanced T stage and 8th AJCC stage were closely associated with the progression of pbt cancers compared with ph cancers. Only one study shows tumor size but not T and clinical stage in 7th AJCC stage exhibits difference in resected ph (56 cases) and pbt (24 cases) cancers , which is consistent with our study. Based on the alteration of T and N status in 8th AJCC stage, T1-3 stage was likely a stratified analysis of tumor size. Meanwhile, new 8th AJCC stage mainly increased III stage (16 vs 0) but decreased IIB stage (86 vs 104) in PC patients compared with 7th AJCC stage in our study, which is the critical reason for the discrimination in above results just as Omar Abdel-Rahman suggested . We additionally found PLM was more frequent in pbt cancers, which is consistent with the study by Maria Chiara Ambrosetti et al . However, Nakata B et al show that the recurrence of peritoneum, liver, lung and bone showed no difference in tumor location . Among 707 unresectable PC patients with stage III, 30.1% developed PLM. However, no risk factors were identified among these patients . The inconsistence might be due to the different sample size and diversity in national population included in different studies.
Currently, prognostic difference between ph and pbt cancer patients remain controversial. Data from SEER database (1988-2004) including 33752 PC patients presents a significant lower median survival (4 months vs 6 months) in patients with pbt cancer compared with those with ph cancer . However, data from the national PC registry of Japan showed a significant lower 5-year survival rate (10.7% vs 13.8%) for patients with ph cancers (n=5788) than those with pbt cancers (n=1629) . Both unresectable and resectable PC patients are enrolled in above studies. In our current study, we only enrolled curatively resected PC patients from three multiple centers. Our study showed that pbt cancer patients had a worse survival compared with ph cancers and was an independent unfavorable prognostic factor. However, a Japanese study enrolling 80 consecutive patients with resectable PC presents similar overall survival and recurrence rates after a curative resection between ph (n=56) and pbt (n=24) cancers . Wentz SC et al. also show no relationship of tumor location (151 ph vs 18 pbt) with resected PC patients . Interestingly, in 43,946 PC patients from SEER registry database, higher survival rates is shown in ph cancer compared with pbt cancer in several variables (age, sex, race, geography, and time). But the 3-year survival rate for local-stage (neoplasm confined to the organ of origin) pbt cancer is 20.0% compared with 9% for local-stage in ph cancer . In 32 PC patients with 7th AJCC stage II, both overall and tumor-free survival were significantly higher in the patients with pbt cancer compared with those with ph cancers . Our study showed that the survival time of pbt cancer patients was longer than that in ph cancer patients only in 8th AJCC I stage but no statistic difference. Indeed, some small metastases (liver metastasis) known as “micrometastases” from PC may be overlooked even with advanced imaging and surgical exploration . In our study, 6 PC patients had a simultaneous single liver metastasis resection that was not detected in preoperative examination. 4 of 6 patients were evaluated in early stage (less than IIA) if we neglected the small single liver metastasis. Generally, pbt cancers were associated with much more advanced stage and worse prognosis in PC patients.
Finally, compared with ph cancers, we first showed tumor size and T stage were not only independent risk factors in the development of pbt cancers, but also poor prognostic indicators based on 8th AJCC stage. Taken together, 8th AJCC stage are more comprehensive to reflect the poor prognosis of pbt cancer patients.
Generally, one limitation in this study is that we don’t have a systematical standardization in surgical procedure and postoperative pathological examination throughout 3 centers, resulting in unstablebilty in lymph node yield, tumor size, and margin status [25, 26]. In addition, the sample size is still small in our current study. That is the reason that some important clinical characters, such as tumor differentiation (P=0.071), only get bordering statistic association with PC patients’ survival. Finally, our study enrolls a few patients with extended R0 resection (combining with surrounding organ resection) in both cohorts that is recommended according to NCCN guidelines but might bring some confounder in current study. Two relatively larger studies show favorable results following hepatic metastasis resection for PC in a highly selected cohort of patients [27, 28]. That is one reason that we enroll 6 cases with synchronous hepatectomy for the single liver metastasis that was not found by pre-operative enhanced CT. Because only 2 and 4 cases of synchronous hepatectomy are included in ph and pbt cohorts, respectively, it has little effect in our statistic results even though we deleted these 6 cases.