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M. Kobari and S. Matsuno: Staging system for pancreatic cancer 121J Hep Bil Pancr Surg (1998) 5:121127

Abstract: Differences between the clinical staging systemof the Japan Pancreas Society (JPS) and the Union Inter-nationale Contre le Cancer (UICC) stage classification mayaccount for reported differences in the prognosis of pancreatic

carcinoma between Japan and the West. In the review, wecompared the characteristics of the JPS and UICC staging in1689 patients, registered with the JPS from 1981 to 1990, whounderwent resection for carcinoma of the pancreatic head.The survival rates correlated well with the JPS stage classifica-tion. The UICC staging did not reflect differences in prog-noses among the stages. The current JPS staging system,introduced in 1993, still differs from that of the UICC. Tocompare the results of treatment for patients with pancreaticcancer it is important to establish a more practical and uni-versal staging system for carcinoma of the pancreas.

Key words:staging, pancreatic cancer, UICC

Introduction

In Japan, the first edition of the General rules for surgi-cal and pathological studies on cancer of pancreaswaspublished 1980,1followed by two revisions the secondedition in 1982,2 and the third edition in 1986.3 Theregistration of pancreatic cancer with the RegistrationCommittee of the Japan Pancreas Society (JPS) wasstarted in 1981 and 11317 patients were registered in the10 years to 1990.4 From evaluation of the results of

treatment for these patients according to stage or histo-logical classification, and with the understanding of newdiseases such as mucin hypersecreting pancreatictumor, a new edition of General rules for Surgical andpathological studies on cancer of pancreas (the fourth

Offprint requests to:M. KobariReceived for publication on Sept 8, 1997; accepted onMarch 25, 1998

edition) was published in 1993.5But there are still somedifferences between the JPS stage classification (JPS-SC)5 and the Union Internationale Contre le Cancer

stage classification (UICC-SC)

6

and these differencesmay account for differences in the prognosis of pancre-atic carcinoma reported in Japan and Western coun-tries. In this review, we compared the JPS-SC in thethird edition of the Generalrules for surgical and patho-logical studies of cancer of pancreas3 with the stageclassification of the UICC6 according to survival ana-lyses in the Report of cases collected during a 10-yearsperiod, as above.4 The features of the current stageclassification of the JPS5are also discussed.

Patients and methods

Staging systems were compared between the thirdedition of the JPS stage classification and the UICCstage grouping. Differences between staging systems inthe third3and fourth editions5of the JPS stage classifica-tion were also analyzed. The new stage groupings forpancreatic cancer published in 1997 by the UICC arealso shown.

Survival analysis

The results of resective treatment were analyzed in 1689

patients with carcinoma of the head of the pancreasregistered with the JPS from 1981 until 1990. The pa-tients who underwent resection were individually classi-fied according to the UICC stage grouping6and the JPSstage classification (third edition3) at the same time bythe attending surgeons according to operative explora-tions or investigation of resected specimens. Both theUICC and the JPS stages were recorded simultaneouslyon record cards and the cards were registered with theRegistration Committee of the JPS. Survival rates werecompared in JPS and UICC stages.

Topics: Staging and treatment for pancreatic cancer

Staging systems for pancreatic cancer: Differences betweenthe Japanese and UICC systems

Masao Kobari andSeiki Matsuno

First Department of Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-77, Japan


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122 M. Kobari and S. Matsuno: Staging system for pancreatic cancer

Fig. 1. Japan Pancreas Society (JPS) stageclassification (third edition).3For all Figs.,see text for explanations of abbreviations

The survival rates of patients treated at the FirstDepartment of Surgery, Tohoku University School ofMedicine in the past 10 years were also compared ac-cording to JPS stages in the third3and fourth edition5ofthe JPS stage classification.

Survival curves were calculated by the Kaplan-Meiermethod. Differences between survival curves wereanalyzed by the generalized Wilcoxon method and thelog-rank test. A probability value of less than 0.05 was

considered to be significant difference.

Results

Stage classification of the JPS (third edition)3

The staging classification for carcinoma of the pancreasas proposed by the JPS is shown in Fig. 1.3This classifi-cation is based on macroscopic examination and eachstage is judged by preoperative imaging diagnosis orsurgical exploration, including macroscopic evaluationof surgical specimen, as in the UICC-SC. T indicates

only the size of the tumor at its greatest dimension. T1is a tumor with a diameter less than 2cm; T2 is a tumorwith a diameter of 24 cm; T3 is a tumor with a diameterof 46cm; T4 is a tumor with a diameter of more than6cm. N indicates lymph node metastasis. N0 indicatesno lymph node involvement. N1 (group 1) is involve-ment of the primary group of lymph nodes situatedclose to the tumor; N2 (group 2) is involvement of thesecondary group of lymph nodes between N1 and N3;N3 (group 3) is involvement of the tertiary group oflymph nodes considered as juxta-regional lymph nodes.S indicates direct anterior capsular invasion. Rp indi-

cates retroperitoneal invasion (fat, connective tissue,nerves, or bile duct). PV designates direct tumor inva-sion of the portal venous systems. S, Rp, and PV areseparated into four groups according to the extent ofextrapancreatic tissue invasion. 0, absence of tumor in-vasion, for example S0, Rp0, PV0; 1, suspected invasion;2, definite invasion; S3, Rp3, and PV3 indicate severeinvasion extending directly to adjacent organs (stomachor colon), retroperitoneum (aorta, superior mesentericartery, inferior vena cava, kidney, or adrenal gland),and portal vein, respectively.

Fig. 2. Union Internationale Contre le Cancer (UICC) stagegrouping (1983)3

Stage I is T1, N0, S0, Rp0, PV0. If any of the stagingfactors T2, N1, S1, Rp1, PV1 are found, the stage is II.If any of the staging factors T3, N2, S2, Rp2, PV2are found, the stage is III. The diagnosis is stage IV ifany of the staging factors T4, N3, S3, Rp3, or PV3 arefound. Distant metastasis, including hepatic metastasisand peritoneal dissemination, is also classified as stageIV.

Criteria for UICC grouping (1987)6and comparison

with JPS staging (third edition)3

The criteria for UICC stage grouping are also shownin the JPS staging3 (Fig. 2).3 The staging factors em-ployed in the UICC-SC are: primary tumor, T; lymphnode metastasis, N; and distant metastasis, M. Assess-ment of each category is made by physical examination,imaging, and/or surgical exploration. In the UICC stag-ing, T includes not only tumor size but also the extent oftumor invasion to tissues surrounding the pancreas. Inthe JPS staging, T means only tumor size, and the extentof tumor invasion is expressed by S, Rp, or PV. InUICC stage I, the tumor is limited to the pancreas (T1)or extends directly to the duodenum, bile duct, or

peripancreatic tissues (T2) without lymph nodemetastasis (N0). In UICC stage II, the tumor extendsdirectly to the stomach, spleen, colon, or adjacent largevessels (T3), but is without lymph node metastasis(N0). In UICC stage III, positive regional lymph nodemetastasis is included (N1). UICC stage IV containsdistant metastasis, including extrapancreatic lymphnode metastasis. In the JPS-SC, we attach as much im-portance to the extent of lymph node metastasis asto the size of the tumor and the extent of invasion toextrapancreatic tissues.


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M. Kobari and S. Matsuno: Staging system for pancreatic cancer 123

T2, Tumors classified as one or more of the following:S1, rP1, PV1, A1, DU1,2,3, and CH2,3, regardlessof size

T3, Tumors classified as one or more of the following:S2,3, rP2,3, PV2,3, and A2,3, regardless of size

The T category in this latest staging system no longerindicates only size. This point is very different from theprevious JPS staging system.3The grading from 0 to 3for category S, category RP, category PV, and categoryN is the same as the system in the third edition.3

However in the fourth edition,5A denotes the arterialsystem, including common hepatic artery, superiormesenteric artery, splenic artery, celiac artery, andaorta. The grading from 0 to 3 for category A is: A0, noevidence of invasion; A1, invasion suspected; A2, defi-nite invasion; and A3, marked invasion with stenosis orobstruction of the arterial system. DU denotes duode-nal wall. The grading from 0 to 3 for category DU is:DU0, no evidence of invasion; DU1, invasion sus-

pected; DU2, definite invasion, but limited to theduodenal wall; and DU3, marked invasion with tumorpenetration into the duodenal lumen or stenosis of theduodenum. CH denotes distal bile duct. The gradingfrom 0 to 3 for category CH is: CH0, no evidence ofinvasion; CH1, invasion suspected; CH2, definite inva-sion; and CH3, marked invasion with stenosis orobstruction of the bile duct. The category P denotesperitoneal metastasis. The grading from 0 to 3 for cat-egory P is: P0, no peritoneal metastasis; P1, metastasisto the peritoneum adjacent to the pancreas; P2, a fewmetastases to distant peritoneum; and P3, numerous

metastases to distant peritoneum. Category H denotesliver metastasis. The grading from 0 to 3 for category His: H0, no liver metastasis; H1, metastasis limited to onelobe; H2, a few metastases to both lobes; H3, numerousmetastases to both lobes. Category M denotes distantmetastasis other than those to peritoneum or liver.

Comparison of survival rates for patients treated

at our university hospital according to the third3

and fourth editions5of the JPS stage classification

For the third edition of the JPS stage classifica-

tion,3

survival curves according to JPS stages were well

Survival rate according to JPS stage classification

(third edition)3

The 3-year survival rates of resected pancreatic headcancer in the 1689 patients registered with the JPSfrom 1981 to 1990 were 66.2% in stage I (n 165),37.2% in stage II (n382), 25.4% in stage III (n474),and 12.7% in stage IV (n668). The 5-year survivalrates were 48.1% in stage I, 27.7% in stage II, 22.3% instage III, and 8.8% in stage IV. The prognosis wasbetter in the early stages of pancreatic cancer and boththe 3- and 5-year survivals showed significant differ-ences between stages I and II and between stages IIIand IV.

Survival rate according to UICC stage grouping (1987)6

Of the 1521 patients with resected pancreatic headcancer for whom all UICC staging factors were accu-rately recorded, 320 patients (21.0%) were in stage I

and 182 patients (12.0%) in stage II. Five hundred andeight-six patients (38.5%) were in stage III and 433(28.5%) in stage IV. The number of patients in UICCstage I was more than two times and the number inUICC stage II was about half compared with the num-bers of patients in stages I and II according to the JPS-SC. The 3-year survival rates were 44.3% in UICC stageI, 22.5% in UICC Stage II, 16.3% in UICC Stage III,and 9.6% in UICC Stage IV. The 5-year survival rateswere 32.5% in UICC stage I, 11.5% in UICC stage II,12.0% in UICC stage III, and 6.6% in UICC stage IV.

Current staging classification of the JPS(fourth edition)5

The current staging system was proposed by the JPS in1993 (Fig. 3).5 The surgical staging is shown in theGeneral rules for surgical and pathological studies on

cancer of the pancreas.5 T categories are assigned ac-cording to the extent of tumor invasion, as follows:

T1, Tumors which are S0, rP0, PV0, A0, DU0, andCH0,1 (see below for definitions)

T1a, Tumors 2.0cm or less at the greatest dimensionT1b, Tumors more than 2.0cm at the greatest

dimension

Fig. 3. Current JPS stage classification(fourth edition)5


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The survival curves according to category N in thefourth edition were well separated between N0 and N1and also between N1 and N2 or N3 (Fig. 5). This differ-ence in survival curves seems better than that in thethird edition.

separated into three groups: stage I, stage II and III, andstage IV. In the fourth edition,5 survival curves werealso divided into three groups: stages I and II, stages IIIand IVa, and stage IVb. For both editions, each stagegroup reflected the prognosis well (Fig. 4).

Fig. 4. Survival rates according to the JPS stage classifications (thirdedition3vs fourthedition5). *P0.01

Fig. 5. Survival rates according to category N in the JPS stage classifications (thirdedition3vs fourthedition5). *P0.01


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The T category in the fourth edition significantly wellreflected the prognosis of the patients (Fig. 6).

New stage grouping proposed by the UICC

(1997)16(Fig. 7)

T categories. Tis, carcinoma in situ; T1, tumor limited to

the pancreas, 2cm or less at greatest dimension; T2,tumor limited to the pancreas, 2cm or more at greatestdimension; T3, tumor extending directly to any of thefollowing: duodenum, bile duct, peripancreatic tissue;T4, tumor extending directly to any of the following:stomach, spleen, colon, adjacent large vessels.N categories. N0, no regional lymph node metastasis;N1, regional lymph node metastasis; N1a, metastasisin a single regional lymph node; N1b, metastasis inmultiple regional lymph nodes.M categories. M0, no distant metastasis; M1, distantmetastasis.

Discussion

Despite advances made in tumor imaging diagnosis, theproportion of patients diagnosed with pancreatic cancerat an early stage has not increased. According to theJapanese report on collected cases in the 10 years to1991,411.7% of 11317 patients were classified as UICC

stage I, 12.1% as stage II, 20.1% as stage III, and 56.1%as stage IV, and resection was performed for 33.1% ofpatients. In the 1994 report on 1133 collected cases,7

15.9% of patients were UICC stage I; 10.4% stage II;30.9% stage III, and 42.8% stage IV; the resection ratewas 43.5%. In our analysis of the 1835 patients whounderwent resection for carcinoma of the head of thepancreas until 1994, 6.1% of patients were classified asJPS stage I and 21.9% as JPS stage II; more than 70%of patients were classified as JPS stage III or IV.7

These stage distributions were comparable to those inThe National Cancer Data Base Report on Pancreatic

Cancer.

8

In our survival analyses of the 1689 patients withresected pancreatic head cancer registered with the JPSfrom 1981 until 1990, the survival rate correlated wellwith the JPS-SC and survivals were longer in patients instage I or II than in patients in stage III or IV (the 5-yearsurvival rate for stage I was 48.1%, for stage II, 27.7%;for stage III, 22.3%; and for stage IV, 8.8%). In theUICC-SC, the survival rate was extremely high for stageI (32.5%) compared with survival rates in other stages(less than 10%) and there was no significant differenceamong survival rates at stages later than stage II.9Thesurvival rate dropped between stage II and stage III.

This pattern of survival rates was very similar to thedifference in survival rates between N0 (high) and N1(low).9The reason for the lack of difference in survivalrates at stages later than stage II seems to be that N inUICC-SC is simply graded as absence of involvement(N0) or presence of involvement (N1). As stated above,in the JPS-SC, we attach as much importance to theextent of lymph node involvement as to the extent of

Fig. 7. New UICC stage grouping(1997)16

Fig. 6. Three- and 5-year survival rates according to categoryT in the JPS stage classification (fourth edition5). *P0.01


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invasion to extrapancreatic tissues. The extent ofmacroscopic lymph node involvement assessed surgi-cally was similar to the extent of histological lymphnode involvement.7

In the UICC-SC, stage I is distinguished from stage IIby the presence or absence of invasion to peripancreaticorgans (stomach, spleen, or colon) or large vessels (T1

or T2 vs T3) and when lymph node involvement is de-tected (N1) the stage is III. If distant metastasis is found(M1) the stage is IV. This staging system is simple, easy,and objective. In the JPS-SC, the extent of LN involve-ment (N) or the extent of peripancreatic tissue invasion(S, Rp, PV) is graded from 0 to 3 and the size of tumor(T) is included in the staging factors.

One difference of the UICC staging system fromthe JPS-SC may be that patients are classified as UICCstage I even when anterior serosal invasion (S) or retro-peritoneal invasion (RP) are found (UICC T23). Un-like the JPS-SC, the UICC-SC gives no clear description

of S-, Rp-, and PV. And the definition of T2 in theUICC-SC is that a tumor shows limited direct extensionto duodenum, bile duct, or peripancreatic tissues; thiscorresponds to S02, Rp02, and PV02, in the JPS-SC.Tsunoda et al.10reported that, with the UICC-SC, thereare some underestimations of the stage, as follows.UICC T2 patients, i.e., patients with definite involve-ment of peripancreatic tissues corresponding to Rp2 inthe JPS-SC, are allocated to UICC stage I. UICC T3patients, who have invasions to the surrounding organsor adjacent large vessels, corresponding to Rp3 andPV23 in the JPS-SC, belong to UICC stage II. In theJPS-SC, the patients with these conditions (S3, Rp3,

and/or PV3) belong to stage IV. This difference indescription concerning extrapancreatic tissue invasionmay account for the difference in survival curvesbetween JPS-SC and UICC-SC, because the survivalrates of patients with S0, patients with Rp0, patientswith PV0, or patients with N0 were much higher thanthose of patients with S13, patients with Rp13, pa-tients with PV13, or patients with N13.9Tannapfel etal.11reported that lymph node involvement and directextension of the tumor into peripancreatic tissue, aswell as invasion into peripancreatic organs, significantlyinfluenced survival. They found no relationship be-

tween survival and tumor size. Zerbi et al.12

evaluatedthe prognostic value of the UICC-SC and JPS-SC in 74patients undergoing resection for pancreatic carcinomaand classified according to both the UICC-SC and JPS-SC at the same time. According to the UICC-SC, therewas a high proportion of patients in stage I (38%) andstage III (39%) and a low proportion in stage II (16%);most patients were in earlier stages compared with thedistribution of patients according to the JPS-SC. Onthe other hand, the distribution of patients according tothe JPS-SC increased as the stage progressed. Survival

curves at each stage were separated well and the differ-ence among the curves was significant for the JPS-SC.However, in the UICC-SC, the survival curves over-lapped at stages II and III. In an analysis of survivalaccording to the UICC-SC in Norwegian patients,Bekkevold and Kambestad13 tested a minor modifica-tion of UICC-SC and showed comparable prognoses for

stages I and II and different prognoses for stages II andIII, contrary to the present UICC-SC. 16Balzano et al.14

evaluated the following modified UICC-SC in their 228patients who underwent resection for pancreatic cancer,and reported a better differentiation of stage II andIII survival than for the standard UICC-SC: Stage I,T1N0M0; stage II, T1N1M0/T2N0M0; stage III,T2N1M0/T3 anyNM0; stage IV, M1. However, theJPS-SC has a greater prognostic value than either thestandard or the modified UICC-SC.

In the current JPS stage classification in the newGeneral rules for surgical and pathological studies on

cancer of the pancreas (4th Edn),

5

tumor size was ex-cluded from the T category, because the survival ratescorrelated well with stages even when the tumor sizewas omitted from the staging.9On graphs of survival,T is shown as the vertical axis, similar to T in theUICC system, but it is graded from 1 to 3 and thisgrading depends on the extent of peripancreatic tissueinvasion, graded from 0 to 3. The Horizontal axis is N,graded from 0 to 3. This grading system is also verydifferent from the UICC staging and is important as, inthe analyses of survival rate among stages classified ac-cording to the JPS-SC, the extent of lymph node in-volvement and of extrapancreatic tissue invasion were

the most important staging factors.4,9In our analyses ofour small series of patients, N, T, and the stages ofthe current JPS stage classification (fourth edition)5re-flected prognosis very well. Therefore, it is expectedthat when many cases are registered with the currentJPS-SC, better differences in survival rates among thestages may be obtained. Last year, the JPS publishedthe first English edition of Classification of pancreaticcarcinoma, which is now in use in Japan.15The UICCalso modified the stage classification of pancreatic can-cer (Fig. 7) evaluated in this study and published a newedition last year.16

There are still differences between the current JPS-SC and the new UICC-SC. To discuss the results oftreatment for pancreatic cancer, it will be necessary toanalyze the survival rates according to a commonstaging system.

References

1. Japanese Pancreas Society (1980) General rules for surgical andpathological studies on cancer of pancreas (in Japanese).Kanehara Publishing, Tokyo


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2. Japanese Pancreas Society (1982) General rules for surgical andpathological studies on cancer of pancreas (in Japanese). 2nd ed.Kanehara Publishing, Tokyo

3. Japanese Pancreas Society (1986) General rules for cancer ofthe pancreas (in Japanese). 3rd ed. Kanehara Publishing,Tokyo

4. Registration Committee of Pancreatic Cancer of Japan PancreasSociety (1991) Annual report of Registration Committee ofPancreatic Cancer 1991. Report of collected cases during 10 years

(in Japanese). Registration Committee of Pancreatic Cancer,Kobe

5. Japanese Pancreas Society (1993) General rules for surgical andpathological studies on cancer of the pancreas (in Japanese). 4thed. Kanehara Publishing, Tokyo

6. Pancreas (ICD-O 157. 03) (1987) UICC TNM Classification ofmalignant Tumors, 4th ed. In: Hermanek P, Sobin LH (eds)Springer, Berlin Heidelberg New York London Paris Tokyo,pp 6567

7. Registration Committee of Pancreatic Cancer of Japan PancreasSociety (1994) Annual report of Registration Committee ofPancreatic Cancer 1994 (in Japanese). J Jpn Pancr Soc 10:535564

8. Niederhuber JE, Brennan M, Menck H (1995) The National Can-cer Data Base Report on Pancreatic Cancer. Cancer 76:16711677

9. Kobari M, Sunamura M, Ohashi O, Saitoh Y, Yusa T, Matsuno S(1996) Usefulness of Japanese staging in the prognosis of patientstreated operatively for adenocarcinoma of the head of the pan-creas. J Am Coll Surg 182:2432

10. Tsunoda T, Ura K, Eto T, Matsumoto T, Tsuchiya R (1991) UICCand Japanese stage classification for carcinoma of the pancreas.Int J Pancreatol 8:205214

11. Tannapfel A, Wittekind C, Hnefeld G (1992) Ductal adeno-carcinoma of the pancreas. Histological features and prognosis.

Int J Pancreatol 12:14515212. Zerbi A, Balzano G, Bottura R, Di Carlo V (1994) Reliability of

pancreatic cancer staging classifications. Int J Pancreatol 15:131813. Bekkevold KE, Kambestad B (1995) Staging of carcinoma of the

pancreas and ampulla of Vater. Tumor (T), lymph node (N), anddistant metastasis (M) as prognostic factors. Int J Pancreatol17:249259

14. Balzano G, Bassi C, Zerbi A, Falconi M, Calori G, Butturini G,Leone BE, Pederzoli P, Di Carlo V (1997) Evaluation of UICCTNM classification for pancreatic cancer. Int J Pancreatol 21:111118

15. Japan Pancreas Society (1996) Classification of pancreatic carci-noma: First English Edition. Kanehara Publishing, Tokyo

16. Pancreas (ICD-O C25.02,8) (1997) UICC TNM Classification ofmalignant tumors, 5th ed. In: Sobin LH, Wittekind C (eds) NewYork, John Wiley and Sons, pp 8790

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