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Carcinoma of the cervix: The staging anomaly
ClmtcalRadiology (1985) 36, 625-628 @1985 RoyalCollegeof Radiologists
0009-9260/85/559625502.00
Carcinoma of the Cervix: The Staging Anomaly W. H. BOND
Consultant Radiotherapist (Retired), Queen Elizabeth Hospital, Birmingham
An analysis of 3625 carcinomas of the cervix treated in Birmingham between 1960 and 1974 showed FIGO staging to be anomalous. State 2B and 3B each contain two subgroups with differing prognosis, depending on whether one or both parametria are involved. Unilateral Stage 2B disease has a prognosis identical with Stage 2A. Bilateral Stage 2B, Stage 3A and unilateral Stage 3B disease have identical survival figures. Stages 1A, 1B and 4 and bilateral Stage 3B disease have unique survival characteristics. A system of staging combining FIGO clinical stages with prognosis facilitates interpretation of treatment results, survival figures and comparisons of series.
An international system of staging for carcinoma of the cervix was introduced in 1929 by the Radiological Subcommission of the League of Nations, who later published an atlas of the stages, basically those employed today. Heyman adopted these stages in the first edition of the Stockholm Reports (League of Nations Health Organization, 1937). When reports were resumed after the last war, personal observation showed Heyman and Kottmeier seeking proof of the accuracy of a more complex staging by each examining the patient during the other's absence and making his own note for later comparison. Clinical findings are still the basis of staging, TNM (UICC, 1978) being seldom applicable as the node state is unknown. The wisdom of FIGO and UICC (1978) staging, their true prognostic value, or intra-stage differences in prognosis, or whether they really represent the macropathological stages of disease in prognostic terms, do not appear to have been questioned. In an attempt to resolve these questions, records of all cases of carcinoma of the cervix treated in the United Birmingham Hospitals or their associated hospitals, including those where peripheral clinics were held between 1960 and 1974 inclusive, were examined and the findings recorded in a database controlled by a CBM 3032 computer. Stage 0 was not included; initially few, after 1969, cases with this stage of disease became too numerous and too uneventful to justify inclusion, leaving 3625 cases in Stages 1A to 4 for analysis. Except for Stages 0 and 1A, which relied on pathological reports, staging was done under anaesthesia when radium was inserted, or from the surgeon's and pathologist's reports, when surgery alone was employed. Other cases were staged on clinical or post-mortem examination. Stages employed were FIGO, viz: Stage 0. Carcinoma in situ. Stage 1A. Microinvasive carcinoma,
Stage lB. Carcinoma confined to os and cervix. Stage 2A, One or more fornices involved. Stage 2B. One or both parametria involved short of the pelvic wall. Stage 3A. Tumour extending to the lower third of the vagina. Stage 3B. One or both parametria involved to the pelvic wall. Stage 4. Metastatic, frozen pelvis, extension outside the pelvis. Stages 2B and 3B disease can both involve one or both parametria so the stages were subdivided into Stage 2 : 1 and Stage 2 : 2, Stage 3 : 1 and Stage 3 : 2, respectively, depending on whether one or both parametria were involved, short of or to the pelvic wall as appropriate to the stage. In Stage 3, involvement of one parametrium to the pelvic wall and proximal involvement of the other parametrium was regarded as Stage 3 : 1. 100
90 80 70
60 50
40 30 20
10 0 12
24
36
48
60
120
MONTHS
Fig. 1 - Survivalcurves to 10 years, 1960to 1974, FIGO staging.
CLINICAL RADIOLOGY
626
100
100
90
90 \
\
80
80
70
70
60 60 % 50 % 50 L
4040
'
COMBINED STAGE
STAGE D 2A
30
b 21+2A
30
21
20 20
P 3A+31*22
31 ~ =
%o
10 ~
""1
3A
\\"
10
~
\,
32
32
12
24
36
48
60
120
MONTHS
12
24
36
48
60
120
MONTHS
Fig. 3 - Combmed modifiedstagesto10ycars, 1960to1974. StageslB and 4 also shown
Fig. 2 - S u r v [ v a l c u r v e s t o 10years, 1960to1974, modlfiedstagmg. StageslA, 1B and4omitted.
STAGE
30
30
1B 2A+21
%20
4~.
~ e 3B
% 20
~
_ . . . . ~
2 2 + 3A-~31
2A
10
10 ..,...,4} 1 A
-"
~
~" 3 A
60-64 60-64
65-69
IA 32
65-69
70-74
70-74
Fig. 4 - Percentage incidence of FIGO stages m the three qumquenma
Fig. 5 - Percentage incidence of modified stages in the three quinquennia.
627
STAGING ANOMALY IN CARCINOMA CERVIX
CONVENTIONAL STAGING The results as staged conventionally appear in Fig. 1. The decline in Stage 1A is almost entirely due to lost cases, only five cases being reported as dying during the period of observation. Stages 1B and 4 clearly differ from other stages and will not be analysed further. Stages 3A and 3B are virtually identical; they differ from Stages 2A and 2B, which differ from each other (p=O.02).
3A and 3 : 1 have 5-year survival rates differing by +2%; Stage 3:2 is completely different from the other two groups of cases. The above groups of cases may, thus, be combined (Fig. 3), revealing three well separated stages with distinctive survival figures. These groups correspond closely with the type of treatment undertaken: 2A and 2:1, radium alone: 2:2, 3A and 3:1 by radium plus megavoltage and 3 : 2 by external radiation alone. CONCLUSION
THE ANOMALY The composite stages 2B and 3B broken down into unilateral disease and bilateral disease were then examined. Stage 2B cases yielded 464 Stage 2:1 and 144 Stage 2 : 2 cases. Stage 3B (649 cases) revealed 468 Stage 3 : 1 and 181 Stage 3 : 2 cases. Survival rates for these revised stages are shown in Fig. 2, including Stages 2A and 3A. In spite of the large numbers, proof of an anomaly is not quite complete. Stages 2:1 and 2:2 differ by 12.8% at 5 years and Stages 3 : 1 and 3 : 2 by 11.9%; in both cases, p=0.06. However, Stages 2:1 and 2A do not differ (p=0.14). Stages 2:2,
This analysis answers the questions clearly. Conventional clinical staging does not truly reflect prognosis, nor take into account intra-stage prognostic differences, or similar prognosis between stages. Two stages are anomalous. Within Stage 2B, unilateral cases (2 : 1) have a prognosis indistinguishable from that of Stage 2A cases. This is hardly unexpected, for the clinical distinction in the presence of a bulky tumour can be difficult to make. Unilateral Stage 3B
100
~
STAGE -
100
STAGE -
8
1A
90
--- 1 A
90 80
80 70 70 60i 60
~
1B
1B
% 5O 2A
% 50
A
40
~
30
=
~
21 * 2A
~
ALLeASES
ALLCASES
40
2B
30 20
"~'~'-.o
22 +3A-31
3B
10
10
32 A
0
-
&
~
60-64
65-69
"t4
70-74
Fig. 6 -- Five-year survival rates in the three quinquennia, F I G O staging.
0
v
,r
60-64
~
65-69
4
70-74
Fig. 7 - Five-year survival rates in the three qumquennia, modified staging.
628
CL1NICAL RADIOLOGY
(3:1) cannot be differentiated from bilateral Stage 2B (2 : 2) or Stage 3A disease in survival terms. The bilateral Stage 3B (3 : 2) group is unique.
Addendum. The series has now been extended to 1979, establishing that Stage 2:1 and 2 : 2 differ significantly (p=0.02). Acknowledgements. To the Radiotherapy Fund, Central Birm i n g h a m Health District for financial support, and to my colleagues throughout the Regions for their reports.
APPLICATION
REFERENCES
The modified staging has two advantages. First, clinical stages with similar prognoses are combined and, secondly, clinical stages with similar treatment methods are combined. The staging facilitates the comparison of the incidence of prognostically similar groups over a period of time. These advantages are shown in Figs 4 and 5: comparing the incidence of stages in the three quinquennia by conventional and modified staging, the simpler and more readily understood appearance of the latter is obvious. For example, as the earlier, radium-treated cases fall in incidence, due to the increased use of cytology and greater allocation to Stage 1A, the other stages show little change; observations not apparent in the conventionally staged figures. Survival rates are also more easily interpreted. Figures 6 and 7 show 5-year rates for the same quinquennia and Fig. 6, using conventional staging, shows confusing results, especially for the last 5 years where there appear to be marked changes in the rates for Stages 2A and 2B. The modified staging used in Fig. 7 reveals that, in fact, the radium-treated cases at Stages 2 : 1 and 2A show a slight rise in survival rate and the real fall lies in Stages 2:2, 2A and 3 : 1, i.e. those receiving both radium and megavoltage therapy. It may be more than a coincidence that there was a rise in the complication rate in the latter group of cases when there were improved megavoltage facilities, amongst other changes. The modified system also gives clinical leads. The similar clinical survival rates in Stages 2A and 2 : 1 suggest that parametrial involvement in Stage 2A is frequent and that, in a narrow vault with poor separation between vaginal sources and a consequently lower midparametrial dose, supplementary external radiation should be employed. Stage 2 : 2, with results identifiable with those from Stage 3:1, emphasises the need for attempts at full local control by external radiation to both parametria out to the pelvic wall.
League of Nations Health Organization (1937). Annual Reports on the Results of Radtotherapy in Cancer o f the Uterine Cervix, ed Heym a n , J., Stockholm. Vol. 1, D o c u m e n t C.H. 1225, Geneva. Radlologlcal Sub-commission of the Cancer Commission of the Health Committee, Health Section, League of Nations (1929). Document C.H. 788: Ser. L.o.N.P. 1929.1ll 5. U I C C (1978). TNM Classification of Mahgnant Turnouts, 3rd edn.
International Union Against Cancer, Geneva. Appendix - Figures (nos ofcases) on which the associated graphs (Figs 1-7) are based Stage
Months survived
Total
12
24
36
48
60
120
25 323 182 157 36 10 118 29 19
25 295 155 123 24 6 83 21 8
25 266 127 103 20 3 69 17 5
25 244 106 88 17 3 55 12 2
25 228 95 78 17 3 48 11 2
24 183 71 55 11 2 38 6 2
25 353 217 179 48 16 167 71 157
60 366 167 133 43 9 102 32 30
58 334 134 106 34 6 69 22 9
57 297 108 88 22 6 58 13 6
57 285 88 81 20 5 50 11 6
57 269 81 74 16 5 44 10 4
53 219 64 48 12 3 29 8 4
60 393 189 162 57 17 144 48 177
77 313 153 93 24 14 108 28 8
74 271 133 68 20 10 74 18 2
74 239 118 60 16 8 51 13 2
74 221 107 51 11 7 45 9 2
73 202 95 43 9 5 36 7 2
67 141 67 29 6 3 23 4 2
78 338 182 123 39 17 157 62 149
1960-64 1A 1B 2A 2:1 2:2 3A 3:1 3:2
4 1965-69 1A 1B 2A 2:1 2:2 3A 3:1 3:2
4 1970-74 1A 1B 2A 2:1 2:2 3A 3:1 3:2 4
0009-9260/85/559625502.00
Carcinoma of the Cervix: The Staging Anomaly W. H. BOND
Consultant Radiotherapist (Retired), Queen Elizabeth Hospital, Birmingham
An analysis of 3625 carcinomas of the cervix treated in Birmingham between 1960 and 1974 showed FIGO staging to be anomalous. State 2B and 3B each contain two subgroups with differing prognosis, depending on whether one or both parametria are involved. Unilateral Stage 2B disease has a prognosis identical with Stage 2A. Bilateral Stage 2B, Stage 3A and unilateral Stage 3B disease have identical survival figures. Stages 1A, 1B and 4 and bilateral Stage 3B disease have unique survival characteristics. A system of staging combining FIGO clinical stages with prognosis facilitates interpretation of treatment results, survival figures and comparisons of series.
An international system of staging for carcinoma of the cervix was introduced in 1929 by the Radiological Subcommission of the League of Nations, who later published an atlas of the stages, basically those employed today. Heyman adopted these stages in the first edition of the Stockholm Reports (League of Nations Health Organization, 1937). When reports were resumed after the last war, personal observation showed Heyman and Kottmeier seeking proof of the accuracy of a more complex staging by each examining the patient during the other's absence and making his own note for later comparison. Clinical findings are still the basis of staging, TNM (UICC, 1978) being seldom applicable as the node state is unknown. The wisdom of FIGO and UICC (1978) staging, their true prognostic value, or intra-stage differences in prognosis, or whether they really represent the macropathological stages of disease in prognostic terms, do not appear to have been questioned. In an attempt to resolve these questions, records of all cases of carcinoma of the cervix treated in the United Birmingham Hospitals or their associated hospitals, including those where peripheral clinics were held between 1960 and 1974 inclusive, were examined and the findings recorded in a database controlled by a CBM 3032 computer. Stage 0 was not included; initially few, after 1969, cases with this stage of disease became too numerous and too uneventful to justify inclusion, leaving 3625 cases in Stages 1A to 4 for analysis. Except for Stages 0 and 1A, which relied on pathological reports, staging was done under anaesthesia when radium was inserted, or from the surgeon's and pathologist's reports, when surgery alone was employed. Other cases were staged on clinical or post-mortem examination. Stages employed were FIGO, viz: Stage 0. Carcinoma in situ. Stage 1A. Microinvasive carcinoma,
Stage lB. Carcinoma confined to os and cervix. Stage 2A, One or more fornices involved. Stage 2B. One or both parametria involved short of the pelvic wall. Stage 3A. Tumour extending to the lower third of the vagina. Stage 3B. One or both parametria involved to the pelvic wall. Stage 4. Metastatic, frozen pelvis, extension outside the pelvis. Stages 2B and 3B disease can both involve one or both parametria so the stages were subdivided into Stage 2 : 1 and Stage 2 : 2, Stage 3 : 1 and Stage 3 : 2, respectively, depending on whether one or both parametria were involved, short of or to the pelvic wall as appropriate to the stage. In Stage 3, involvement of one parametrium to the pelvic wall and proximal involvement of the other parametrium was regarded as Stage 3 : 1. 100
90 80 70
60 50
40 30 20
10 0 12
24
36
48
60
120
MONTHS
Fig. 1 - Survivalcurves to 10 years, 1960to 1974, FIGO staging.
CLINICAL RADIOLOGY
626
100
100
90
90 \
\
80
80
70
70
60 60 % 50 % 50 L
4040
'
COMBINED STAGE
STAGE D 2A
30
b 21+2A
30
21
20 20
P 3A+31*22
31 ~ =
%o
10 ~
""1
3A
\\"
10
~
\,
32
32
12
24
36
48
60
120
MONTHS
12
24
36
48
60
120
MONTHS
Fig. 3 - Combmed modifiedstagesto10ycars, 1960to1974. StageslB and 4 also shown
Fig. 2 - S u r v [ v a l c u r v e s t o 10years, 1960to1974, modlfiedstagmg. StageslA, 1B and4omitted.
STAGE
30
30
1B 2A+21
%20
4~.
~ e 3B
% 20
~
_ . . . . ~
2 2 + 3A-~31
2A
10
10 ..,...,4} 1 A
-"
~
~" 3 A
60-64 60-64
65-69
IA 32
65-69
70-74
70-74
Fig. 4 - Percentage incidence of FIGO stages m the three qumquenma
Fig. 5 - Percentage incidence of modified stages in the three quinquennia.
627
STAGING ANOMALY IN CARCINOMA CERVIX
CONVENTIONAL STAGING The results as staged conventionally appear in Fig. 1. The decline in Stage 1A is almost entirely due to lost cases, only five cases being reported as dying during the period of observation. Stages 1B and 4 clearly differ from other stages and will not be analysed further. Stages 3A and 3B are virtually identical; they differ from Stages 2A and 2B, which differ from each other (p=O.02).
3A and 3 : 1 have 5-year survival rates differing by +2%; Stage 3:2 is completely different from the other two groups of cases. The above groups of cases may, thus, be combined (Fig. 3), revealing three well separated stages with distinctive survival figures. These groups correspond closely with the type of treatment undertaken: 2A and 2:1, radium alone: 2:2, 3A and 3:1 by radium plus megavoltage and 3 : 2 by external radiation alone. CONCLUSION
THE ANOMALY The composite stages 2B and 3B broken down into unilateral disease and bilateral disease were then examined. Stage 2B cases yielded 464 Stage 2:1 and 144 Stage 2 : 2 cases. Stage 3B (649 cases) revealed 468 Stage 3 : 1 and 181 Stage 3 : 2 cases. Survival rates for these revised stages are shown in Fig. 2, including Stages 2A and 3A. In spite of the large numbers, proof of an anomaly is not quite complete. Stages 2:1 and 2:2 differ by 12.8% at 5 years and Stages 3 : 1 and 3 : 2 by 11.9%; in both cases, p=0.06. However, Stages 2:1 and 2A do not differ (p=0.14). Stages 2:2,
This analysis answers the questions clearly. Conventional clinical staging does not truly reflect prognosis, nor take into account intra-stage prognostic differences, or similar prognosis between stages. Two stages are anomalous. Within Stage 2B, unilateral cases (2 : 1) have a prognosis indistinguishable from that of Stage 2A cases. This is hardly unexpected, for the clinical distinction in the presence of a bulky tumour can be difficult to make. Unilateral Stage 3B
100
~
STAGE -
100
STAGE -
8
1A
90
--- 1 A
90 80
80 70 70 60i 60
~
1B
1B
% 5O 2A
% 50
A
40
~
30
=
~
21 * 2A
~
ALLeASES
ALLCASES
40
2B
30 20
"~'~'-.o
22 +3A-31
3B
10
10
32 A
0
-
&
~
60-64
65-69
"t4
70-74
Fig. 6 -- Five-year survival rates in the three quinquennia, F I G O staging.
0
v
,r
60-64
~
65-69
4
70-74
Fig. 7 - Five-year survival rates in the three qumquennia, modified staging.
628
CL1NICAL RADIOLOGY
(3:1) cannot be differentiated from bilateral Stage 2B (2 : 2) or Stage 3A disease in survival terms. The bilateral Stage 3B (3 : 2) group is unique.
Addendum. The series has now been extended to 1979, establishing that Stage 2:1 and 2 : 2 differ significantly (p=0.02). Acknowledgements. To the Radiotherapy Fund, Central Birm i n g h a m Health District for financial support, and to my colleagues throughout the Regions for their reports.
APPLICATION
REFERENCES
The modified staging has two advantages. First, clinical stages with similar prognoses are combined and, secondly, clinical stages with similar treatment methods are combined. The staging facilitates the comparison of the incidence of prognostically similar groups over a period of time. These advantages are shown in Figs 4 and 5: comparing the incidence of stages in the three quinquennia by conventional and modified staging, the simpler and more readily understood appearance of the latter is obvious. For example, as the earlier, radium-treated cases fall in incidence, due to the increased use of cytology and greater allocation to Stage 1A, the other stages show little change; observations not apparent in the conventionally staged figures. Survival rates are also more easily interpreted. Figures 6 and 7 show 5-year rates for the same quinquennia and Fig. 6, using conventional staging, shows confusing results, especially for the last 5 years where there appear to be marked changes in the rates for Stages 2A and 2B. The modified staging used in Fig. 7 reveals that, in fact, the radium-treated cases at Stages 2 : 1 and 2A show a slight rise in survival rate and the real fall lies in Stages 2:2, 2A and 3 : 1, i.e. those receiving both radium and megavoltage therapy. It may be more than a coincidence that there was a rise in the complication rate in the latter group of cases when there were improved megavoltage facilities, amongst other changes. The modified system also gives clinical leads. The similar clinical survival rates in Stages 2A and 2 : 1 suggest that parametrial involvement in Stage 2A is frequent and that, in a narrow vault with poor separation between vaginal sources and a consequently lower midparametrial dose, supplementary external radiation should be employed. Stage 2 : 2, with results identifiable with those from Stage 3:1, emphasises the need for attempts at full local control by external radiation to both parametria out to the pelvic wall.
League of Nations Health Organization (1937). Annual Reports on the Results of Radtotherapy in Cancer o f the Uterine Cervix, ed Heym a n , J., Stockholm. Vol. 1, D o c u m e n t C.H. 1225, Geneva. Radlologlcal Sub-commission of the Cancer Commission of the Health Committee, Health Section, League of Nations (1929). Document C.H. 788: Ser. L.o.N.P. 1929.1ll 5. U I C C (1978). TNM Classification of Mahgnant Turnouts, 3rd edn.
International Union Against Cancer, Geneva. Appendix - Figures (nos ofcases) on which the associated graphs (Figs 1-7) are based Stage
Months survived
Total
12
24
36
48
60
120
25 323 182 157 36 10 118 29 19
25 295 155 123 24 6 83 21 8
25 266 127 103 20 3 69 17 5
25 244 106 88 17 3 55 12 2
25 228 95 78 17 3 48 11 2
24 183 71 55 11 2 38 6 2
25 353 217 179 48 16 167 71 157
60 366 167 133 43 9 102 32 30
58 334 134 106 34 6 69 22 9
57 297 108 88 22 6 58 13 6
57 285 88 81 20 5 50 11 6
57 269 81 74 16 5 44 10 4
53 219 64 48 12 3 29 8 4
60 393 189 162 57 17 144 48 177
77 313 153 93 24 14 108 28 8
74 271 133 68 20 10 74 18 2
74 239 118 60 16 8 51 13 2
74 221 107 51 11 7 45 9 2
73 202 95 43 9 5 36 7 2
67 141 67 29 6 3 23 4 2
78 338 182 123 39 17 157 62 149
1960-64 1A 1B 2A 2:1 2:2 3A 3:1 3:2
4 1965-69 1A 1B 2A 2:1 2:2 3A 3:1 3:2
4 1970-74 1A 1B 2A 2:1 2:2 3A 3:1 3:2 4