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Carcinoma of the cervix: The effect of age on survival
GYNECOLOGIC
ONCOLOGY
Carcinoma
10,
188-193 (1980)
of the Cervix: The Effect of Age on Survival
C. ROBERTSTANHOPE,M.D.,’ JULIAN P. SMITH, M.D.,J. TAYLOR WHARTON, M.D.,* FELIX N. RUTLEDGE,M.D. ,* GILBERT H. FLETCHER, M.D. ,* AND H. STEPHENGALLAGER, M.D.* Department of Gynecology and Obstetrics, Wayne State University School of Medicine, Detroit, Michigan 48202, and *University of Texas System Cancer Center, Houston, Texas 77030
Received January 11, 1980 A significant decrease in S-year survival was found in 265 patients with invasive cervical cancer under the age of 35 compared to 820 over the age of 35 in all stages except Stage I-A and Stage IV. The exact reasons for the differences remain obscure. The greatest number of failures occurred in Stage II-B patients where, despite central control of disease, distant metastases developed. This suggests that the pretreatment evaluation of younger patients, especially those with Stage II-B cancer, should be more aggressive at attempts to detect cancer beyond the usual treatment fields. The poorer prognosis for patients under age 35 could not be explained on the basis of cell type. It was found that patients with large-cell, keratinizing cancers had a somewhat improved survival over patients with large-cell, nonkeratinizing cancers.
Invasive cervical carcinona is frequently discovered in younger females. The literature contains conflicting data relating to the survival of younger patients with invasive cervical carcinoma. In 1952, a report from the Radiumhemmet on a large series of patients with invasive carcinoma showed that 5-year survival improves with increasing age for all stages. The patients were stage-grouped and corrections were made for deaths from intercurrent disease [l]. No predilection for more anaplastic tumors in the younger age groups was noted. Then, in 1955, a Mayo Clinic review of 1451 patients with invasive cervical carcinoma failed to show any significant difference in stage-grouped survival among 169 women under the age of 35 and those over 35. Irradiation therapy was the primary form of treatment in all except 12 of the younger patients who underwent surgery [2]. The purpose of this study is to compare survival in patients with invasive cervical carcinoma of an intact uterus under age 35 with patients over age 35. Both the younger and older groups were treated with irradiation therapy or surgery using the same guidelines and principles of treatment. All patients treated for cure within the study periods were included. i To whom requests for reprints should be addressed at: Department of Gynecology and Obstetrics, Hutzel Hospital, 4707 St. Antoine, Detroit, Mich. 48201. 188 0090-8258/80/050188~06$01.00/O Copyright All tights
@ IWO by Academic Press, Inc. of reproduction in any form reserved.
EFFECT
OF AGE
ON
SURVIVAL
IN
CERVICAL
CANCER
189
FIG0 staging for cervical cancer emphasizes the extent of tumor involvement to a greater degree than it emphasizes quantity or volume of cancer. In the analysis of patients in this paper, Stage I-B cancer is divided into “low volume” (invasive carcinoma with only one quadrant histologically positive) and “high volume” (invasive carcinoma with two or more quadrants histologically positive or an endocervical lesion with expansion of the endocervix). MATERIALS
AND METHODS
Two thousand one hundred and fifty-eight patients with invasive cervical carcinoma of an intact uterus were treated at the University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute at Houston, Texas, between January 1960, and December 1970. Two hundred and sixty-five of these patients (12.3%) were under age 35; the youngest patient was 18 years old. Age 35 was selected as a cutoff point for this group because it separates the active reproductive period and marks a point above which the age incidence for cervical carcinoma sharply rises. All patients in this group were followed for 5 or more years after diagnosis and none were lost to follow-up. Of the remaining 1910 patients 916 received their treatment between January 1964 and December 1969, and were part of an analysis by Jampolis et al. for causes and sites of treatment failure [3]. For the purpose of this study, 820 of the patients over 35 included in Jampolis’ report will comprise the older group. These patients were followed for a minimum of 44 years; and more than 90% of the patients were followed for 5 years when Jampolis analyzed this group of patients. TREATMENT
AND RESULTS
Irradiation therapy was used most frequently as the primary treatment in both groups of patients. The analysis of the treatment used in the group under 35 is shown in Table 1. The irradiation techniques used in both groups of patients was the same and has been described in publications by Fletcher 151. The 5-year survival for the 265 patients under 35 and for the 820 patients over 35 is shown in Table 2. Corrections in survival for deaths from intercurrent disease were made. A x2 analysis was used as a test to determine if a 5-year survival was independent of age as defined by under age 35 and over age 35. The x2 values were significant at the 5% level for stages considered separately. In fact, Stages 1-B (high volume), II-A, II-B, and III were highly significant (P < 0.005). The difference in survival between Stage I-A and Stage IV was not significant because only 6 patients over age 35 had Stage I-A disease and all patients with Stage IV cancer died of their disease. In the younger group, 42 patients (15.8%) had small-volume cancer with early invasion of the cervical stroma and were treated with surgery alone. There was only one treatment failure in this group of patients. Adjunctive conservative extrafascial hysterectomy was performed in 6 additional patients with large, bulky, endocervical Stage I cancer following a somewhat less radical dose of irradiation. Three of these patients developed distant metastases and died. The other 3 survived. Seven patients with advanced carcinoma were treated primarily with chemotherapy alone or with irradiation. The remaining 216 patients received primary irradiation therapy.
190
STANHOPE ET AL.
TABLE 1 THERAPYFORYOUNGERAND OLDER PATIENTS WITH INTACT
A. Irradiation therapy Subtotal
INVASIVE
CARCINOMA
OF AN
Less than 35
Over 35
216 216
806 806
B. Surgery alone Cone biopsy Class I hysterectomya Class II hysterectomy’ Class III hysterectomy’ Radical vaginal hysterectomy Subtotal
1 22 8 10 1 42
C. Other (chemotherapy alone or with irradiation therapy in advanced cases)
I
Total
CERVICAL
UTERUS
265
6 8 14
820
a Reference (4).
In the older group of patients, only 14 were treated primarily with surgery. The remaining 806 received irradiation therapy. Sites of failure are described in Fig. 1. The sites of failure for each stage are presented in Table 3. It is not relevant to consider sites of failure in most patients with Stage IV disease because the therapy is usually considered palliative. Sixteen (11.4%) patients with Stage I cancer developed recurrences. One patient with microinvasive carcinoma developed distant metastatic disease and died. There was only one central failure in patients with Stage I cervical cancer. Nelson reported a reduction in the central recurrence rate from 15 to 3% in patients with bulky endocervical lesions when conservative hysterectomy was added to slightly less radical radiotherapy [6]. Six patients in the “under 35” group with “barrel-shaped” lesions in this series were subjected to adjunctive hysterectomy. There were no central failures. Regional failures occurred with greater frequency in patients under 35 with Stage II-A lesions than in those with Stage II-B lesions. Distant metastases occurred in nearly 80% of Stage II-B failures. Of the 19 Stage II-B failures, 12 had infiltrating exocervical lesions and 7 had endocervical barrel-shaped lesions. Three of the latter group were treated with adjunctive conservative hysterectomy and all 3 developed distant metastases. (This illustrates the fact that adjunctive hysterectomy has reduced the incidence of central failures only.) In patients with Stage III involvement, central disease was controlled in all but 1 patient. The other Stage III failures were evenly distributed between regional and distant failure sites. Fourty-four of the two hundred and fifty-six patients (17%) under 35 were pregnant or within 3 months postpartum when treatment was begun. Table 4 shows the breakdown by stage of those who were pregnant or postpartum. The total survival of the younger group of patients and those associated with preg-
EFFECT
OF AGE
ON
SURVIVAL
IN
CERVICAL
191
CANCER
TABLE 2 SQUAMOUS CARCINOMA OF THE CERVIX ON INTACT UTERUS~-YEAR SURVIVAL-FIG0
35 Years and less
STAGING
Over 35 years
(Surv. ‘0)
(No.)
(Surv. %)
(No.1
P
Stage I-A Stage I-B (low volume) Stage I-B (high volume)
98.0 85.7 76.4
(42) (49)
(52)
100.0 %.3 91.3
(6) (62) VW
0.05 0.005
Stage II-A Stage II-B
51.4 40.0
(37) (42)
83.6 65.6
(160)
(176)
0.005 0.005
Stage III
25.5
(35)
47.1
(207)
0.05
(8)
-
(1)
-
Stage IV Total
265
-
820
nancy reflects the more advanced stages seen in the patients who were pregnant. The number of pregnant patients was too small for an accurate comparison of survival between pregnant and nonpregnant patients stage by stage. Creasman reported 113 pregnant patients with invasive cervical carcinoma from M. D. Anderson Hospital and found that within a given stage the survival rate was not appreciably different between pregnant and nonpregnant patients [7]. DISCUSSION
Wentz and Reagan have subdivided cervical cancer into large-cell nonkeratinizing, large-cell keratinizing, and small-cell types [S]. They suggest that large-cell TABLE 3 SITES OF FAILURE BY STAGE IN 60 PATIENTS LESS THAN 35 YEARS OLD Cen
Stage I-A Stage I-B (low volume) Stage I-B (high volume)
-
Stage II-A Stage II-B Stage III-A Stage III-B
-
DM
Cen DM
2 2
-
1 2 4
-
4 1
3 -
3 15
-
5
-
3 2
-
1
-
Cen Reg
Reg
1 -
Reg DM
Total
1 3
1 6 9
2 3
13 19
-
1
-
9 3
1 0
Note. Central Disease (Cen): Failure in the vault of the vagina (upper two-thirds) or the remaining uterus, indicated by ulceration with a positive biopsy usually obtainable. Regional Disease (Reg): Failure anywhere in the pelvic structure or in the regional lymphatics located at the actual pelvic brim or overlying the upper aspects of the sacroiliac joints. The diagnosis of regional disease was determined through clinical examination or surgical exploration. Distant Metastases (DM): Objective evidence such as palpation of hard, enlarged inguinal or supraclavicular lymph nodes, progressive or multiple chest nodules, mediastinal or hilar nodes, bony destruction, nodular enlarged liver, malignant ascites, etc.
192
STANHOPE ET AL. TABLE 4 INCIDENCE OF PREGNANCY IN 265 PATIENTS LESS THAN 35 YEARS OLD
Stage I Stage II Stage III Stage IV 5-Year survival rate
Total no. (%)
No. preg. (%)
143 (54) 79 (30) 35 (13) 8 (3) 265
19 (43) 19 (43) 6 (14) O44
61%
55%
Note. Comparison of survival between total group and pregnant patients.
nonkeratinizing cancers resemble the more mature cells of normal stratified squamous mucosa on the basis of size and, therefore, consider lesions of that cellular type to be well differentiated. Keratin, on the other hand, is not normally observed in cervical mucosa so they feel keratinization represents loss of differentiation. The small-cell carcinoma is most unlike the normal stratified squamous mucosa and is clearly the least differentiated type of cervical carcinoma. These authors subdivided 95 patients by cell type and reported 2-year survival data, showing that patients with large-cell nonkeratinizing carcinoma survived longer than those with large-cell keratinizing or small-cell carcinoma, supporting their theories. In an attempt to explain the decreased survival of patients under 35, we reviewed the original pathology of 194of the 265 patients and grouped the patients according to cell types. Survival rates were calculated and are shown in Table 5. When we subdivided our patients by cell type, we found that the greatest number of patients had large-cell nonkeratinizing cancer. TABLE 5 CELL TYPE AND SURVIVAL
Wentz and Reagan
M.D.A.H.’
No. (%)
2-year survival (%I
No. (%)
5 year survival (%)
Large cell, keratinizing
23 (24.2)
62.2
65 (31.9)
70.8
Large cell, nonkeratinizing
42 (44.2)
83.3
110 (53.9)
49.0
Small cell
30 (31.6)
46.6
19 (9.3)
52.4b
Total
95 (100)
194 (100)
Nore. Comparison of M. D. Anderson Hospital with literature. LI M. D. Anderson Hospital. b The small number of patients available for analysis lessens the reliability of this statistic.
EFFECT
OF AGE
ON
SURVIVAL
IN
CERVICAL
CANCER
193
Our data do not reflect the same finding reported by Wentz and Reagan. In this group of patients, the presence of keratin resulted in an improved survival. The 5-year survival of 65 patients with large-cell keratinizing carcinoma was 70.8% and for 110 patients with large-cell nonkeratinizing carcinoma was 49.0%. Of patients with small-cell carcinoma, 52.4% survived for 5 years. CONCLUSIONS
1. Using a uniform staging system and treatment plan in two large series of patients with invasive cervical carcinoma of the intact uterus, a significant difference in survival was found between patients under 35 and those over 35 years old. The exact reasons for the differences remain obscure. Differences in etiology or spread of cervical cancer in the younger patients, or perhaps immunologic differences or differences in tumor virulence, may be the explanation. These differences may disable the host mechanisms that control microscopic spread of disease. 2. The greatest number of failures occurred in Stage II-B patients where, despite central control of disease, distant metastases developed. This suggests that the pretreatment evaluation of younger patients, especially those with Stage II-B cancer, should be more aggressive in attempts to detect cancer beyond the usual treatment field. Such tools as lymphangiography with percutaneous lymph node biopsies need to be employed routinely. Possibly, programs using adjunctive chemotherapy, immunotherapy, or intraoperative paraaortic irradiation need further trial and evaluation. 3. An analysis of survival by cell type showed that patients with large-cell keratinizing cancers have a somewhat improved survival over patients with large-cell nonkeratinizing cancers. Because of the small number of patients within each stage group, the data regarding the effect of cell type on survival are not conclusive. REFERENCES 1. Lindell, A. Carcinoma of the uterine cervix-incidence and influence of age, Acta. Radial. 92, 1 (1952). 2. Decker, D. G., Fricke, R. E., and Pratt, J. H. Invasive carcinoma of the cervix in young women, J. Amer. Med. Assoc. 158, 1417-1420 (1955). 3. Jampolis, S., Andras, E. J., and Fletcher, G. H. Analysis of the sites and causes of failures of irradiation in invasive squamous cell carcinoma of the intact uterine cervix, Radiology 115, 681-685 (1975). 4. Piver, M. S., Rutledge, F. N., and Smith, J. P. Five classes of extended hysterectomy for women with cervical cancer, Obster. Gynecol. 44, 265-272 (1974). 5. Fletcher, G. H. Textbook of radiotherapy, Lea & Febiger, Philadelphia, pp. 620-655 (1973). 6. Nelson, A. J., III, Fletcher, G. H., and Wharton, J. T. Indications for adjunctive conservative extrafascial hysterectomy in selected cases of carcinoma of the uterine cervix, Amer. J. Roentgenol. 123, 91-99 (1975). 7. Creasman, W. T., Rutledge, F. N., and Fletcher, G. H. Carcinoma of the cervix associated with pregnancy, Obstet. Gynecol. 36, 495-501 (1970). 8. Wentz, W. B., and Reagan, J. W. Survival in cervical cancer with respect to cell type, Cancer 12, 385-388 (1959).
ONCOLOGY
Carcinoma
10,
188-193 (1980)
of the Cervix: The Effect of Age on Survival
C. ROBERTSTANHOPE,M.D.,’ JULIAN P. SMITH, M.D.,J. TAYLOR WHARTON, M.D.,* FELIX N. RUTLEDGE,M.D. ,* GILBERT H. FLETCHER, M.D. ,* AND H. STEPHENGALLAGER, M.D.* Department of Gynecology and Obstetrics, Wayne State University School of Medicine, Detroit, Michigan 48202, and *University of Texas System Cancer Center, Houston, Texas 77030
Received January 11, 1980 A significant decrease in S-year survival was found in 265 patients with invasive cervical cancer under the age of 35 compared to 820 over the age of 35 in all stages except Stage I-A and Stage IV. The exact reasons for the differences remain obscure. The greatest number of failures occurred in Stage II-B patients where, despite central control of disease, distant metastases developed. This suggests that the pretreatment evaluation of younger patients, especially those with Stage II-B cancer, should be more aggressive at attempts to detect cancer beyond the usual treatment fields. The poorer prognosis for patients under age 35 could not be explained on the basis of cell type. It was found that patients with large-cell, keratinizing cancers had a somewhat improved survival over patients with large-cell, nonkeratinizing cancers.
Invasive cervical carcinona is frequently discovered in younger females. The literature contains conflicting data relating to the survival of younger patients with invasive cervical carcinoma. In 1952, a report from the Radiumhemmet on a large series of patients with invasive carcinoma showed that 5-year survival improves with increasing age for all stages. The patients were stage-grouped and corrections were made for deaths from intercurrent disease [l]. No predilection for more anaplastic tumors in the younger age groups was noted. Then, in 1955, a Mayo Clinic review of 1451 patients with invasive cervical carcinoma failed to show any significant difference in stage-grouped survival among 169 women under the age of 35 and those over 35. Irradiation therapy was the primary form of treatment in all except 12 of the younger patients who underwent surgery [2]. The purpose of this study is to compare survival in patients with invasive cervical carcinoma of an intact uterus under age 35 with patients over age 35. Both the younger and older groups were treated with irradiation therapy or surgery using the same guidelines and principles of treatment. All patients treated for cure within the study periods were included. i To whom requests for reprints should be addressed at: Department of Gynecology and Obstetrics, Hutzel Hospital, 4707 St. Antoine, Detroit, Mich. 48201. 188 0090-8258/80/050188~06$01.00/O Copyright All tights
@ IWO by Academic Press, Inc. of reproduction in any form reserved.
EFFECT
OF AGE
ON
SURVIVAL
IN
CERVICAL
CANCER
189
FIG0 staging for cervical cancer emphasizes the extent of tumor involvement to a greater degree than it emphasizes quantity or volume of cancer. In the analysis of patients in this paper, Stage I-B cancer is divided into “low volume” (invasive carcinoma with only one quadrant histologically positive) and “high volume” (invasive carcinoma with two or more quadrants histologically positive or an endocervical lesion with expansion of the endocervix). MATERIALS
AND METHODS
Two thousand one hundred and fifty-eight patients with invasive cervical carcinoma of an intact uterus were treated at the University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute at Houston, Texas, between January 1960, and December 1970. Two hundred and sixty-five of these patients (12.3%) were under age 35; the youngest patient was 18 years old. Age 35 was selected as a cutoff point for this group because it separates the active reproductive period and marks a point above which the age incidence for cervical carcinoma sharply rises. All patients in this group were followed for 5 or more years after diagnosis and none were lost to follow-up. Of the remaining 1910 patients 916 received their treatment between January 1964 and December 1969, and were part of an analysis by Jampolis et al. for causes and sites of treatment failure [3]. For the purpose of this study, 820 of the patients over 35 included in Jampolis’ report will comprise the older group. These patients were followed for a minimum of 44 years; and more than 90% of the patients were followed for 5 years when Jampolis analyzed this group of patients. TREATMENT
AND RESULTS
Irradiation therapy was used most frequently as the primary treatment in both groups of patients. The analysis of the treatment used in the group under 35 is shown in Table 1. The irradiation techniques used in both groups of patients was the same and has been described in publications by Fletcher 151. The 5-year survival for the 265 patients under 35 and for the 820 patients over 35 is shown in Table 2. Corrections in survival for deaths from intercurrent disease were made. A x2 analysis was used as a test to determine if a 5-year survival was independent of age as defined by under age 35 and over age 35. The x2 values were significant at the 5% level for stages considered separately. In fact, Stages 1-B (high volume), II-A, II-B, and III were highly significant (P < 0.005). The difference in survival between Stage I-A and Stage IV was not significant because only 6 patients over age 35 had Stage I-A disease and all patients with Stage IV cancer died of their disease. In the younger group, 42 patients (15.8%) had small-volume cancer with early invasion of the cervical stroma and were treated with surgery alone. There was only one treatment failure in this group of patients. Adjunctive conservative extrafascial hysterectomy was performed in 6 additional patients with large, bulky, endocervical Stage I cancer following a somewhat less radical dose of irradiation. Three of these patients developed distant metastases and died. The other 3 survived. Seven patients with advanced carcinoma were treated primarily with chemotherapy alone or with irradiation. The remaining 216 patients received primary irradiation therapy.
190
STANHOPE ET AL.
TABLE 1 THERAPYFORYOUNGERAND OLDER PATIENTS WITH INTACT
A. Irradiation therapy Subtotal
INVASIVE
CARCINOMA
OF AN
Less than 35
Over 35
216 216
806 806
B. Surgery alone Cone biopsy Class I hysterectomya Class II hysterectomy’ Class III hysterectomy’ Radical vaginal hysterectomy Subtotal
1 22 8 10 1 42
C. Other (chemotherapy alone or with irradiation therapy in advanced cases)
I
Total
CERVICAL
UTERUS
265
6 8 14
820
a Reference (4).
In the older group of patients, only 14 were treated primarily with surgery. The remaining 806 received irradiation therapy. Sites of failure are described in Fig. 1. The sites of failure for each stage are presented in Table 3. It is not relevant to consider sites of failure in most patients with Stage IV disease because the therapy is usually considered palliative. Sixteen (11.4%) patients with Stage I cancer developed recurrences. One patient with microinvasive carcinoma developed distant metastatic disease and died. There was only one central failure in patients with Stage I cervical cancer. Nelson reported a reduction in the central recurrence rate from 15 to 3% in patients with bulky endocervical lesions when conservative hysterectomy was added to slightly less radical radiotherapy [6]. Six patients in the “under 35” group with “barrel-shaped” lesions in this series were subjected to adjunctive hysterectomy. There were no central failures. Regional failures occurred with greater frequency in patients under 35 with Stage II-A lesions than in those with Stage II-B lesions. Distant metastases occurred in nearly 80% of Stage II-B failures. Of the 19 Stage II-B failures, 12 had infiltrating exocervical lesions and 7 had endocervical barrel-shaped lesions. Three of the latter group were treated with adjunctive conservative hysterectomy and all 3 developed distant metastases. (This illustrates the fact that adjunctive hysterectomy has reduced the incidence of central failures only.) In patients with Stage III involvement, central disease was controlled in all but 1 patient. The other Stage III failures were evenly distributed between regional and distant failure sites. Fourty-four of the two hundred and fifty-six patients (17%) under 35 were pregnant or within 3 months postpartum when treatment was begun. Table 4 shows the breakdown by stage of those who were pregnant or postpartum. The total survival of the younger group of patients and those associated with preg-
EFFECT
OF AGE
ON
SURVIVAL
IN
CERVICAL
191
CANCER
TABLE 2 SQUAMOUS CARCINOMA OF THE CERVIX ON INTACT UTERUS~-YEAR SURVIVAL-FIG0
35 Years and less
STAGING
Over 35 years
(Surv. ‘0)
(No.)
(Surv. %)
(No.1
P
Stage I-A Stage I-B (low volume) Stage I-B (high volume)
98.0 85.7 76.4
(42) (49)
(52)
100.0 %.3 91.3
(6) (62) VW
0.05 0.005
Stage II-A Stage II-B
51.4 40.0
(37) (42)
83.6 65.6
(160)
(176)
0.005 0.005
Stage III
25.5
(35)
47.1
(207)
0.05
(8)
-
(1)
-
Stage IV Total
265
-
820
nancy reflects the more advanced stages seen in the patients who were pregnant. The number of pregnant patients was too small for an accurate comparison of survival between pregnant and nonpregnant patients stage by stage. Creasman reported 113 pregnant patients with invasive cervical carcinoma from M. D. Anderson Hospital and found that within a given stage the survival rate was not appreciably different between pregnant and nonpregnant patients [7]. DISCUSSION
Wentz and Reagan have subdivided cervical cancer into large-cell nonkeratinizing, large-cell keratinizing, and small-cell types [S]. They suggest that large-cell TABLE 3 SITES OF FAILURE BY STAGE IN 60 PATIENTS LESS THAN 35 YEARS OLD Cen
Stage I-A Stage I-B (low volume) Stage I-B (high volume)
-
Stage II-A Stage II-B Stage III-A Stage III-B
-
DM
Cen DM
2 2
-
1 2 4
-
4 1
3 -
3 15
-
5
-
3 2
-
1
-
Cen Reg
Reg
1 -
Reg DM
Total
1 3
1 6 9
2 3
13 19
-
1
-
9 3
1 0
Note. Central Disease (Cen): Failure in the vault of the vagina (upper two-thirds) or the remaining uterus, indicated by ulceration with a positive biopsy usually obtainable. Regional Disease (Reg): Failure anywhere in the pelvic structure or in the regional lymphatics located at the actual pelvic brim or overlying the upper aspects of the sacroiliac joints. The diagnosis of regional disease was determined through clinical examination or surgical exploration. Distant Metastases (DM): Objective evidence such as palpation of hard, enlarged inguinal or supraclavicular lymph nodes, progressive or multiple chest nodules, mediastinal or hilar nodes, bony destruction, nodular enlarged liver, malignant ascites, etc.
192
STANHOPE ET AL. TABLE 4 INCIDENCE OF PREGNANCY IN 265 PATIENTS LESS THAN 35 YEARS OLD
Stage I Stage II Stage III Stage IV 5-Year survival rate
Total no. (%)
No. preg. (%)
143 (54) 79 (30) 35 (13) 8 (3) 265
19 (43) 19 (43) 6 (14) O44
61%
55%
Note. Comparison of survival between total group and pregnant patients.
nonkeratinizing cancers resemble the more mature cells of normal stratified squamous mucosa on the basis of size and, therefore, consider lesions of that cellular type to be well differentiated. Keratin, on the other hand, is not normally observed in cervical mucosa so they feel keratinization represents loss of differentiation. The small-cell carcinoma is most unlike the normal stratified squamous mucosa and is clearly the least differentiated type of cervical carcinoma. These authors subdivided 95 patients by cell type and reported 2-year survival data, showing that patients with large-cell nonkeratinizing carcinoma survived longer than those with large-cell keratinizing or small-cell carcinoma, supporting their theories. In an attempt to explain the decreased survival of patients under 35, we reviewed the original pathology of 194of the 265 patients and grouped the patients according to cell types. Survival rates were calculated and are shown in Table 5. When we subdivided our patients by cell type, we found that the greatest number of patients had large-cell nonkeratinizing cancer. TABLE 5 CELL TYPE AND SURVIVAL
Wentz and Reagan
M.D.A.H.’
No. (%)
2-year survival (%I
No. (%)
5 year survival (%)
Large cell, keratinizing
23 (24.2)
62.2
65 (31.9)
70.8
Large cell, nonkeratinizing
42 (44.2)
83.3
110 (53.9)
49.0
Small cell
30 (31.6)
46.6
19 (9.3)
52.4b
Total
95 (100)
194 (100)
Nore. Comparison of M. D. Anderson Hospital with literature. LI M. D. Anderson Hospital. b The small number of patients available for analysis lessens the reliability of this statistic.
EFFECT
OF AGE
ON
SURVIVAL
IN
CERVICAL
CANCER
193
Our data do not reflect the same finding reported by Wentz and Reagan. In this group of patients, the presence of keratin resulted in an improved survival. The 5-year survival of 65 patients with large-cell keratinizing carcinoma was 70.8% and for 110 patients with large-cell nonkeratinizing carcinoma was 49.0%. Of patients with small-cell carcinoma, 52.4% survived for 5 years. CONCLUSIONS
1. Using a uniform staging system and treatment plan in two large series of patients with invasive cervical carcinoma of the intact uterus, a significant difference in survival was found between patients under 35 and those over 35 years old. The exact reasons for the differences remain obscure. Differences in etiology or spread of cervical cancer in the younger patients, or perhaps immunologic differences or differences in tumor virulence, may be the explanation. These differences may disable the host mechanisms that control microscopic spread of disease. 2. The greatest number of failures occurred in Stage II-B patients where, despite central control of disease, distant metastases developed. This suggests that the pretreatment evaluation of younger patients, especially those with Stage II-B cancer, should be more aggressive in attempts to detect cancer beyond the usual treatment field. Such tools as lymphangiography with percutaneous lymph node biopsies need to be employed routinely. Possibly, programs using adjunctive chemotherapy, immunotherapy, or intraoperative paraaortic irradiation need further trial and evaluation. 3. An analysis of survival by cell type showed that patients with large-cell keratinizing cancers have a somewhat improved survival over patients with large-cell nonkeratinizing cancers. Because of the small number of patients within each stage group, the data regarding the effect of cell type on survival are not conclusive. REFERENCES 1. Lindell, A. Carcinoma of the uterine cervix-incidence and influence of age, Acta. Radial. 92, 1 (1952). 2. Decker, D. G., Fricke, R. E., and Pratt, J. H. Invasive carcinoma of the cervix in young women, J. Amer. Med. Assoc. 158, 1417-1420 (1955). 3. Jampolis, S., Andras, E. J., and Fletcher, G. H. Analysis of the sites and causes of failures of irradiation in invasive squamous cell carcinoma of the intact uterine cervix, Radiology 115, 681-685 (1975). 4. Piver, M. S., Rutledge, F. N., and Smith, J. P. Five classes of extended hysterectomy for women with cervical cancer, Obster. Gynecol. 44, 265-272 (1974). 5. Fletcher, G. H. Textbook of radiotherapy, Lea & Febiger, Philadelphia, pp. 620-655 (1973). 6. Nelson, A. J., III, Fletcher, G. H., and Wharton, J. T. Indications for adjunctive conservative extrafascial hysterectomy in selected cases of carcinoma of the uterine cervix, Amer. J. Roentgenol. 123, 91-99 (1975). 7. Creasman, W. T., Rutledge, F. N., and Fletcher, G. H. Carcinoma of the cervix associated with pregnancy, Obstet. Gynecol. 36, 495-501 (1970). 8. Wentz, W. B., and Reagan, J. W. Survival in cervical cancer with respect to cell type, Cancer 12, 385-388 (1959).