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Site of recurrence of cervical cancer after radical hysterectomy
Site of recurrence of cervical cancer after radical hysterectomy MAURICE
J.
WEBB, M.D.
RICHARD E. SYMMONDS, M.D. Rol'h1'1fer. ll1inntlofr~
Of 564 patients who underwent radical hysterectomies for cervical cancer, 104 had recurrences. Twenty (3.5%) had recurrence in the central pelvis, and in nine (1.6%), this was the only site of recurrence. Of the patients who had lymph node metastases at the time of radical hysterectomy, 40% subsequently had recurrence compared with 14% who had negative nodes and recurrence. The site of recurrence, however, had no relationship to lymph node involvement, size of the lesion, stage of disease, cell type or grade, or previous pelvic irradiation. (AM. J. OBSTET. GYNECOL. 138:813, 1980.)
MosT REPORTS on the treatment of cervical cancer. by either radical surgery or irradiation, tend to concentrate on survival and complications of treatment as a means of assessing the effectiveness of treatment. A factor often overlooked is the site of recurrence. A recurrence in the central pelvis, whether after radical hvsterectomy or pelvic irradiation, and especially if there is no spread of disease beyond the treated area. must be regarded as a reliable indicator of the effectiveness of treatment. Material
The series involved 564: patients with cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy at the Mayo Clinic from 1956 through 1975. Cancer of tht• cervix accounted for 92.5% of all radical hysterectomies performed during this period (Table 1). Most of the patients had Stage IB (53.9%) and Stage IIA (:.!I.:\%) lesions (Table II). Of the 564 patients, 14 I had previou~ irradiation as their primary treatment. and radical hysterectomy was being performed as a "salvage'' procedure for radioresistant or recurrent dist~ase. <)f the 564 patients, Hl. 7% had squamous cell cancers and 15. I 17c: had adenocarcinomas. 1
From the Division uj Gynecologic Surgery, Mayo Clinic and Mayo Foundation. Rn~ivt'd
for publiwtion May 2, /980.
Amptf'djuly 30, 1980.
Reprint requests: Dr. Maurice]. Webb, Mavo Clinic, Rochester, l'vlinnesota 55901. 0002-!1~7Ri8012:\0813+05$00.50/0
©
1980 The C. V. Mosby Co.
Results Of the :164 patients, 104 ( lR.4%) had recurrent cervical cancer (Table III). Central pelvic recurrence developed in 20 instances (3.5%), but in onlv nine instances ( 1.6%) was the central pelvis the only site of recurrence. An initial analvsis was performed on each of four major subgroups to endeavor to determine if any particular characteristic of the tumor predisposed the patient to recurrent disease in each of the four major sites: central pelvis, pelvic sidewall, abdominal cavity, and other sites (lung. bone, distant nodes, .md so forth) (Table IV). Size of lesion. The size of the cervical tumor was not always recorded by the pathologist, hut 1\hen this information was available. tumors were placed into two groups according to greatest diameter. Of the 17 patients with central recurrences, 11 (65%) had tumors of 4 em or less, but overall the groups were fairly evenlv distributed, and statistical analysis showed no significant difference in relation to size of the lesion. Stage of disease. Because many of these patients had had radiotherapy as their primary treatment at other institutions and \Vere referred to our clinic with recurrent disease, the initial clinical stage was J.vailable for only ~H of the 104 patients. No signiticante was attributed to initial stage of disease in relation to site ot recurrence. Previous radiation therapy. Of the 104 patients with recurrent disease, 36 had had previous pelvic irradiation. and because these patients alreadv had recurrent central pelvic tumor (that being the reason they un813
814 Webb and Symmonds Am
Table l. Distribution of patients according to sites of origin of cancer
Derembet l. !\ill!! Obst~t. (;mew!.
J.
Table III. Distribution of patients according to sites of recurrence
Patients Site
No.
%
Cervix Endometrium Vagina Vulva Colon Breast
564 27* 15* 2
92.5 4.4 2.4 0.3 0.2 0.2
I I
*One patient also had squamous cell carcinoma of the vulva.
Table II. Distribution of patients according to stage of disease in cancer of the cervix
No.
%
IV Unknown
59 304 120 21 9* I* 3* 47*
10.5 53.9 21.3 3.7 1.6 0.2 0.5 8.3
Total
564
100.0
IA IB IIA liB IliA
IIIB
Other:
*All had previously received radiotherapy.
derwent radical hysterectomy), a higher percentage of previously irradiated patients in the central recurrence group (55%) is expected when compared with the overall incidence (35%). However, statistical analysis did not reveal any significant relationship between site of recurrence and previous radiation therapy. One might expect fewer pelvic recurrences (central and sidewall) in the previously irradiated group owing to the sterilizing effect of the radiation treatments within the treated field. This was not so, as 38% of the patients with pelvic recurrences had had previous irradiation, the explanation being that operation was performed because radiotherapy had failed to control the disease. Cell type. No significant difference in sites of recurrence could be found when squamous cell carcinoma was compared with adenocarcinoma of the cervix. Adenoc4rcinomas accounted for 10% of the central pelvic recurrences and 15% of all pelvic (central and sidewall) disease, being similar to the overall incidence of adenocarcinoma in the series ( 15%). Histologic grade. In the whole series of 564 cancers of the cervix, 80% had high-grade tumors (Broders grades 3 and 4), and there were 85% high-grade tumors in the group of 104 recurrences. However,
20 9
2 9 41 10
31 18 13 .5 2.5
Lung Lung and other Nodes Vulva and perineum Total
Patients Stage
Central: Pelvis Plus distant Plus sidewall Sidewall: Plus distant Alone Abdominal: Cavity Cavity and other
9 .5 8 3
104
there was no significant difference when site of recurrence was compared with grade of tumor. Lymph node involvement. No significant differences were found between positive nodes and site of recurrence. However, when the 104 patients with recurrent disease were compared with the 460 patients who did not develop recurrence, 40% of those with positive nodes subsequently developed recurrence. compared with only 14% (65 patients) of those patients with noninvolved nodes. This was a highly significant difference (P < 0.0001) (Table V). Interestingly, the patients in whom pelvic sidewall recurrence developed had the highest incidence of positive nodes at hysterectomy (41.5%). This may be due to the failure to remove all involved lymphatic tissue at operation, thus predisposing the patient to recurrence in this region.
Reassessment Because no relationships were found when recurrences were grouped into the previously mentioned four categories, data were reassessed by dividing the recurrences into three groups: ( 1) central pelvic disease only, (2) regional disease (disease involving the central pelvis and sidewall or sidewall alone but not outside the pelvis), and (3) distant disease (disease that may or may not involve the pelvis but is outside the pelvis) (Table VI). Size of lesion. Large cervical lesions did not predispose to central recurrence, and the ratios were evenly distributed in the "regional" and "distant" categories. Stage of disease. No significant differences could be found among the various categories. Previous radiation therapy. Although most recurrences in the total group were noted in the patients not previously irradiated (and this applied also to the "regional" and "distant" groups), "central" recurrences
Cervical cancer recurrence after radical hysterectomy
Volume 1:1~ \Jumbt-r 7, Part I
815
Table IV. Comparison of factors and sites of recurrence in patients with cervical cancer who had ll!Hkrgune radical hvsterectomy Site Central
Abdominal
~f
_,
recu.rren(e
Fotal
Other
Sidewall
Lfsion sizr (em):
-s4 >4
Total
11 6 17
2 6 8
6
16
9 7 0 0 16
II 9 20
7 II 18
17 2 1 20
!7
14
H
35
15 29
6
:\3 iiR
14
Lesion Stal{e:
I II Ill I\' rota!
8
2 0
13
~l9
I
II II I
I
()
I
33
23
Hk
12 29
ti
36
19
fiR
41
25
104
34
H6
104
til
IH
l4
·1
Prevww trmtment:
Radiation No radiation rota! Cell type: Squamous
Adenocarcinoma Other Iotai
()
()
i8
4i
!8 5 2 2.5
3 12 5 20
3 II 4 !8
7 25
3 13
9
9
27
41
25
!04
5 15 20
7 II 18
17 24 4I
]()
~19
15 25
65
7
15 'l
Le1·ion grade:
I and2 3 4 ·rota! Lvmph nodes:
Positive Negative Total
were evenly distributed. This is also probably influenced by this highly selected group who had failure of radiotherapy yet had a surgically removable, centrally recurrent tumor. Patients who had not had irradiation before radical hysterectomy were also analyzed independently, with the use of all of the above criteria. Again, no significant differences were found. Cell type. No significant differences in recurrence were noted between cell types. Histologic grade. Histologic grade did not influence the site of recurrence. Lymph node involvement. Only one patient in the group with purely central pelvic recurrences ( 11 %) had lymph node metastasis at lymphadenectomy, and this patient had only one metastatically involved node. A higher percentage of patients in the "regional" (35%) and "distant" (43%) groups had node metastasis atoperation, but there was no statistical difference between the groups. Percentage vaginectomy. The percentage vaginectomy was assessed and was used as a measure of how radical the procedure was. Central recurrences were more frequent when more than 25% of the vagina was
16
104
Table V. Relation of recurrence to nodal involvement in patients with cervical cancer who had undergone radical hysterectomy D~~~·-~~~~n
Ilt:LUIIt:fU.r::
Lymph nodes
Yes
Positive Negative Total
39 65 104
I
No
Total
58 402 460
97 467 564
excised; however. this difference was not statistically significant. Survival. Only six (5.7%) of the 104 patients have survived their recurrent disease. Although this percentage appears to be very low, only nine of the 104 had recurrent disease that was confined to the central pelvis, and these nine are the only patients who were potentially salvageable by pelvic exenteration. However, all nine patients died of disease. Calame, 2 in reviewing 193 recurrent cervical cancers, noted a survival rate of 4. l %. The steep slopes of the survival curve reHect the short survival of the patients in each group once there was recurrence (Fig. I).
816
Webb and Symmonds
Dt·r~mbt·t
.\rn.
70
Q)
:. 50
:::::
Site of recurrence -
Q)
Central N =20 A" .4240 Deaths= 20
........ Other n =25 A=.2602
111
....c:
40
~ Q) Q.
30
I. I ~li'tl Olhtt'l. (;\'IH!•>I.
Table VI. Comparison ot factors and sites of recurrence in patients with cervical cancer who had undergone radical hysterectomy
80
60
J.
-
Deaths=22
Sidewall n =41 A=.2636 Deaths=39
--- Abdominal n = 18 A= .3481 Deaths= 17
Central
IRegional IDistrml
Total
Lfsiun size (em):
-s4 >4 l"otal
6
3 9
14 13 27
15 17 32
14 18
22 24
Lesion Stage: I II Ill IV
2 I 0
Total
:~
35 :-~:1
68 39
44 4
l
2
I
()
I
6
34
48
88
5 4
18
9
13 27 40
37 55
36 6S 104
6 3 9
35 5 40
45 10 55
86 18 104
2 7
6 34 40
8 47 55
16 88 104
26 7 7 40
31 15
65 23 16 104
Previous treatment: 20
Radiation No radiation Total Cell type:
Squamous Other Total Lesion grade:
I and 2 3 and 4 Total
9
Positive lymph nodes:
Fig. 1. Survival of patients according to site of recurrence of cervical cancer after radical hysterectomy.
Comment Central pelvic recurrences must be the main reference point for judging the adequacy of both operation and radiotherapy for cervical cancer. Obviously, if the cervical tumor cannot be excised with wide margins of normal tissue, then local recurrence is likely. Unfortunately, with cervical cancer, the close approximation of the ureters, bladder, and rectum requires compromising this surgical principle, and avoiding these structures may result in an inadequate radical procedure. A central recurrence rate of only 1.6% in this series of 564 radical hysterectomies shows that the degree of radicality of the procedure which we are performing is satisfactory. Even when one includes the other 11 patients who had central disease as well as disease elsewhere (nine within the pelvis and two distant), the central recurrence rate is 3.5%. However, recurrence that develops simultaneously at other sites along with the central lesion probably is a measure of the biological behavior of the tumor rather than the adequacy of surgical resection. Even when irradiation is used as the primary method of treatment, central recurrence has been a problem. Cullhed 3 reported a recurrence rate of 5.6% after irradiation for Stage IB lesions and a rate of 7.7% for
None
8
I
I
2:2 Total
()
9
9
55
Portion of vagina excised:
None to 25% 2:26% Total
3 5 8
3
8
:~7
40
45 53
14 87 101
0 9 9
2 38 40
4 51 55
98 104
Patient status:
Alive Dead Total
(j
Stage IIA lesions. Johnsson, 4 using the Stockholm technique, had a local recurrence rate of 6% in Stage IB and 14% in Stage IIA at 2 years after treatment. Durrance and associates" reported a central recurrence rate of 1. 9% at M. D. Anderson Hospital in 4 71 patients who had Stage I disease treated by radiotherapy and a rate of 5.6% in patients with Stage II disease. The authors noted an improvement with the advent of megavoltage equipment, a fact also reported by VillaSanta6 and Halpin and associates. 7 In our series, lesion size was relatively unimportant with regard to site of recurrence. Graham and Graham, 8 Piver and Chung, 9 and Van Nagell and associates'0 have shown a relationship between lesion size and the incidence of lymph node metastasis and recurrence. TheM. D. Anderson group 5 also reported problems with central recurrences in patients with large, "barrel-shaped" lesions who were treated radio-
Cervical cancer recurrence after rad1cal hysterectomy 817
Volum< 1:\8 )\:umht'r 7, Part
therapeutically, and they found that the addition of conservative hysterectomy significantly reduced these recurrences. However, in our series, twice as many central recurrences were noted in patients who had lesions of -l ern or less in diameter compared with patients who had lesions greater than -t em in diameter. This finding is not unrt>asonable, because although larger lesions can make the operation more difficult technically, if the primary tumor mass is resected adequately and the extent of dissection is not compromised, central recurrences should not be more frequent when the lesions are larger. The nine patients with "central recurrence alone"
are the ones who are of great concern because they are most likely to signifv technical failure oft he treatment method. Five of these patients had previous irradiation as their primarv treatment, and because of failure of this modality, they underwent operation. or the four nonirradiated patients, none underwent postoperative pehic irradiation. The initial stage o! disease:' in two patients was unknown. three had Stage Ill disease, two had Stage IIA disease, one had Stage I IB dist'ase. and one had Stage lilA disease. The averag-e time until recurrence for these nine patienh was 14 months, with a range of 4 to :W months.
REFERENCES
J., and Symmonds, R. E.: Wertheim hysterectomy: a reappraisal, Obstet. Gynecol. 54:140, 1979. Calame, R. J.: Recurrent carcinoma of the cervix, AM. J. 0BSTET. GYNECOL. 105:380, 1969. Cullhed, S.: Carcinoma cervicis uteri stages I and Ila: treatment-histopathology-prognosis, Acta Obstet. Gyneml. Scand. (Suppl.) 75: I, 1978. Johnsson, J. E.: Squamous cell carcinoma of the uterine cervix. Acta Radio!. (Ther.) (Stockh.) 16:33, 1977. Durrance, F. Y .. Fletcher, G. H., and Rutledge, F. N.: Analysis of central recurrent disease in stages I and II
I. Webb. M.
2. :l.
4.
5.
souantous cell cr~rrinomas nf the cervix on int;:~ct uteru'> Am . .J. Roe~;g~~~X 106;831, 1969. . . .. . ..... '
ti. VillaSanta, U.: Radium and external irradiation versus radiun1 and operation for early invasive carcinon1a of the
uterine cervix. AM.
J.
0BSTET. GYNECOL. 106:498, 1970.
7. Halpin, T. F., Frick, H. C .. II, and Munnell. E. W.: Critical points of failure in the therapy of canfer of the cervix: A reappraisal, AM . .J. OBSTET. GYNECOL. 114:755, 1972. 8. Graham, J. B., and Graham, R. M.: The sensitization response in patients with cancer of the uterine cervix, Cancer 13:5, 1960. 9. Piver, M.S., and Chung, W. S.: Prognostic significance of cervical lesion size and pelvic node metast;tses in cervical carcinoma, Obstet. Gynecol. 46:507, 1975. 10. Van Nagell, J. R., Jr., Donaldson, E. S., Parker, J. C .. van Dyke, A. H., and Wood, E. G.: The prognostic significance of cell tvoe and lesion size in oatients with cervical cancer treat~d by radical mrger;. (~meml. On col. 5:142. 1977.
J.
WEBB, M.D.
RICHARD E. SYMMONDS, M.D. Rol'h1'1fer. ll1inntlofr~
Of 564 patients who underwent radical hysterectomies for cervical cancer, 104 had recurrences. Twenty (3.5%) had recurrence in the central pelvis, and in nine (1.6%), this was the only site of recurrence. Of the patients who had lymph node metastases at the time of radical hysterectomy, 40% subsequently had recurrence compared with 14% who had negative nodes and recurrence. The site of recurrence, however, had no relationship to lymph node involvement, size of the lesion, stage of disease, cell type or grade, or previous pelvic irradiation. (AM. J. OBSTET. GYNECOL. 138:813, 1980.)
MosT REPORTS on the treatment of cervical cancer. by either radical surgery or irradiation, tend to concentrate on survival and complications of treatment as a means of assessing the effectiveness of treatment. A factor often overlooked is the site of recurrence. A recurrence in the central pelvis, whether after radical hvsterectomy or pelvic irradiation, and especially if there is no spread of disease beyond the treated area. must be regarded as a reliable indicator of the effectiveness of treatment. Material
The series involved 564: patients with cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy at the Mayo Clinic from 1956 through 1975. Cancer of tht• cervix accounted for 92.5% of all radical hysterectomies performed during this period (Table 1). Most of the patients had Stage IB (53.9%) and Stage IIA (:.!I.:\%) lesions (Table II). Of the 564 patients, 14 I had previou~ irradiation as their primary treatment. and radical hysterectomy was being performed as a "salvage'' procedure for radioresistant or recurrent dist~ase. <)f the 564 patients, Hl. 7% had squamous cell cancers and 15. I 17c: had adenocarcinomas. 1
From the Division uj Gynecologic Surgery, Mayo Clinic and Mayo Foundation. Rn~ivt'd
for publiwtion May 2, /980.
Amptf'djuly 30, 1980.
Reprint requests: Dr. Maurice]. Webb, Mavo Clinic, Rochester, l'vlinnesota 55901. 0002-!1~7Ri8012:\0813+05$00.50/0
©
1980 The C. V. Mosby Co.
Results Of the :164 patients, 104 ( lR.4%) had recurrent cervical cancer (Table III). Central pelvic recurrence developed in 20 instances (3.5%), but in onlv nine instances ( 1.6%) was the central pelvis the only site of recurrence. An initial analvsis was performed on each of four major subgroups to endeavor to determine if any particular characteristic of the tumor predisposed the patient to recurrent disease in each of the four major sites: central pelvis, pelvic sidewall, abdominal cavity, and other sites (lung. bone, distant nodes, .md so forth) (Table IV). Size of lesion. The size of the cervical tumor was not always recorded by the pathologist, hut 1\hen this information was available. tumors were placed into two groups according to greatest diameter. Of the 17 patients with central recurrences, 11 (65%) had tumors of 4 em or less, but overall the groups were fairly evenlv distributed, and statistical analysis showed no significant difference in relation to size of the lesion. Stage of disease. Because many of these patients had had radiotherapy as their primary treatment at other institutions and \Vere referred to our clinic with recurrent disease, the initial clinical stage was J.vailable for only ~H of the 104 patients. No signiticante was attributed to initial stage of disease in relation to site ot recurrence. Previous radiation therapy. Of the 104 patients with recurrent disease, 36 had had previous pelvic irradiation. and because these patients alreadv had recurrent central pelvic tumor (that being the reason they un813
814 Webb and Symmonds Am
Table l. Distribution of patients according to sites of origin of cancer
Derembet l. !\ill!! Obst~t. (;mew!.
J.
Table III. Distribution of patients according to sites of recurrence
Patients Site
No.
%
Cervix Endometrium Vagina Vulva Colon Breast
564 27* 15* 2
92.5 4.4 2.4 0.3 0.2 0.2
I I
*One patient also had squamous cell carcinoma of the vulva.
Table II. Distribution of patients according to stage of disease in cancer of the cervix
No.
%
IV Unknown
59 304 120 21 9* I* 3* 47*
10.5 53.9 21.3 3.7 1.6 0.2 0.5 8.3
Total
564
100.0
IA IB IIA liB IliA
IIIB
Other:
*All had previously received radiotherapy.
derwent radical hysterectomy), a higher percentage of previously irradiated patients in the central recurrence group (55%) is expected when compared with the overall incidence (35%). However, statistical analysis did not reveal any significant relationship between site of recurrence and previous radiation therapy. One might expect fewer pelvic recurrences (central and sidewall) in the previously irradiated group owing to the sterilizing effect of the radiation treatments within the treated field. This was not so, as 38% of the patients with pelvic recurrences had had previous irradiation, the explanation being that operation was performed because radiotherapy had failed to control the disease. Cell type. No significant difference in sites of recurrence could be found when squamous cell carcinoma was compared with adenocarcinoma of the cervix. Adenoc4rcinomas accounted for 10% of the central pelvic recurrences and 15% of all pelvic (central and sidewall) disease, being similar to the overall incidence of adenocarcinoma in the series ( 15%). Histologic grade. In the whole series of 564 cancers of the cervix, 80% had high-grade tumors (Broders grades 3 and 4), and there were 85% high-grade tumors in the group of 104 recurrences. However,
20 9
2 9 41 10
31 18 13 .5 2.5
Lung Lung and other Nodes Vulva and perineum Total
Patients Stage
Central: Pelvis Plus distant Plus sidewall Sidewall: Plus distant Alone Abdominal: Cavity Cavity and other
9 .5 8 3
104
there was no significant difference when site of recurrence was compared with grade of tumor. Lymph node involvement. No significant differences were found between positive nodes and site of recurrence. However, when the 104 patients with recurrent disease were compared with the 460 patients who did not develop recurrence, 40% of those with positive nodes subsequently developed recurrence. compared with only 14% (65 patients) of those patients with noninvolved nodes. This was a highly significant difference (P < 0.0001) (Table V). Interestingly, the patients in whom pelvic sidewall recurrence developed had the highest incidence of positive nodes at hysterectomy (41.5%). This may be due to the failure to remove all involved lymphatic tissue at operation, thus predisposing the patient to recurrence in this region.
Reassessment Because no relationships were found when recurrences were grouped into the previously mentioned four categories, data were reassessed by dividing the recurrences into three groups: ( 1) central pelvic disease only, (2) regional disease (disease involving the central pelvis and sidewall or sidewall alone but not outside the pelvis), and (3) distant disease (disease that may or may not involve the pelvis but is outside the pelvis) (Table VI). Size of lesion. Large cervical lesions did not predispose to central recurrence, and the ratios were evenly distributed in the "regional" and "distant" categories. Stage of disease. No significant differences could be found among the various categories. Previous radiation therapy. Although most recurrences in the total group were noted in the patients not previously irradiated (and this applied also to the "regional" and "distant" groups), "central" recurrences
Cervical cancer recurrence after radical hysterectomy
Volume 1:1~ \Jumbt-r 7, Part I
815
Table IV. Comparison of factors and sites of recurrence in patients with cervical cancer who had ll!Hkrgune radical hvsterectomy Site Central
Abdominal
~f
_,
recu.rren(e
Fotal
Other
Sidewall
Lfsion sizr (em):
-s4 >4
Total
11 6 17
2 6 8
6
16
9 7 0 0 16
II 9 20
7 II 18
17 2 1 20
!7
14
H
35
15 29
6
:\3 iiR
14
Lesion Stal{e:
I II Ill I\' rota!
8
2 0
13
~l9
I
II II I
I
()
I
33
23
Hk
12 29
ti
36
19
fiR
41
25
104
34
H6
104
til
IH
l4
·1
Prevww trmtment:
Radiation No radiation rota! Cell type: Squamous
Adenocarcinoma Other Iotai
()
()
i8
4i
!8 5 2 2.5
3 12 5 20
3 II 4 !8
7 25
3 13
9
9
27
41
25
!04
5 15 20
7 II 18
17 24 4I
]()
~19
15 25
65
7
15 'l
Le1·ion grade:
I and2 3 4 ·rota! Lvmph nodes:
Positive Negative Total
were evenly distributed. This is also probably influenced by this highly selected group who had failure of radiotherapy yet had a surgically removable, centrally recurrent tumor. Patients who had not had irradiation before radical hysterectomy were also analyzed independently, with the use of all of the above criteria. Again, no significant differences were found. Cell type. No significant differences in recurrence were noted between cell types. Histologic grade. Histologic grade did not influence the site of recurrence. Lymph node involvement. Only one patient in the group with purely central pelvic recurrences ( 11 %) had lymph node metastasis at lymphadenectomy, and this patient had only one metastatically involved node. A higher percentage of patients in the "regional" (35%) and "distant" (43%) groups had node metastasis atoperation, but there was no statistical difference between the groups. Percentage vaginectomy. The percentage vaginectomy was assessed and was used as a measure of how radical the procedure was. Central recurrences were more frequent when more than 25% of the vagina was
16
104
Table V. Relation of recurrence to nodal involvement in patients with cervical cancer who had undergone radical hysterectomy D~~~·-~~~~n
Ilt:LUIIt:fU.r::
Lymph nodes
Yes
Positive Negative Total
39 65 104
I
No
Total
58 402 460
97 467 564
excised; however. this difference was not statistically significant. Survival. Only six (5.7%) of the 104 patients have survived their recurrent disease. Although this percentage appears to be very low, only nine of the 104 had recurrent disease that was confined to the central pelvis, and these nine are the only patients who were potentially salvageable by pelvic exenteration. However, all nine patients died of disease. Calame, 2 in reviewing 193 recurrent cervical cancers, noted a survival rate of 4. l %. The steep slopes of the survival curve reHect the short survival of the patients in each group once there was recurrence (Fig. I).
816
Webb and Symmonds
Dt·r~mbt·t
.\rn.
70
Q)
:. 50
:::::
Site of recurrence -
Q)
Central N =20 A" .4240 Deaths= 20
........ Other n =25 A=.2602
111
....c:
40
~ Q) Q.
30
I. I ~li'tl Olhtt'l. (;\'IH!•>I.
Table VI. Comparison ot factors and sites of recurrence in patients with cervical cancer who had undergone radical hysterectomy
80
60
J.
-
Deaths=22
Sidewall n =41 A=.2636 Deaths=39
--- Abdominal n = 18 A= .3481 Deaths= 17
Central
IRegional IDistrml
Total
Lfsiun size (em):
-s4 >4 l"otal
6
3 9
14 13 27
15 17 32
14 18
22 24
Lesion Stage: I II Ill IV
2 I 0
Total
:~
35 :-~:1
68 39
44 4
l
2
I
()
I
6
34
48
88
5 4
18
9
13 27 40
37 55
36 6S 104
6 3 9
35 5 40
45 10 55
86 18 104
2 7
6 34 40
8 47 55
16 88 104
26 7 7 40
31 15
65 23 16 104
Previous treatment: 20
Radiation No radiation Total Cell type:
Squamous Other Total Lesion grade:
I and 2 3 and 4 Total
9
Positive lymph nodes:
Fig. 1. Survival of patients according to site of recurrence of cervical cancer after radical hysterectomy.
Comment Central pelvic recurrences must be the main reference point for judging the adequacy of both operation and radiotherapy for cervical cancer. Obviously, if the cervical tumor cannot be excised with wide margins of normal tissue, then local recurrence is likely. Unfortunately, with cervical cancer, the close approximation of the ureters, bladder, and rectum requires compromising this surgical principle, and avoiding these structures may result in an inadequate radical procedure. A central recurrence rate of only 1.6% in this series of 564 radical hysterectomies shows that the degree of radicality of the procedure which we are performing is satisfactory. Even when one includes the other 11 patients who had central disease as well as disease elsewhere (nine within the pelvis and two distant), the central recurrence rate is 3.5%. However, recurrence that develops simultaneously at other sites along with the central lesion probably is a measure of the biological behavior of the tumor rather than the adequacy of surgical resection. Even when irradiation is used as the primary method of treatment, central recurrence has been a problem. Cullhed 3 reported a recurrence rate of 5.6% after irradiation for Stage IB lesions and a rate of 7.7% for
None
8
I
I
2:2 Total
()
9
9
55
Portion of vagina excised:
None to 25% 2:26% Total
3 5 8
3
8
:~7
40
45 53
14 87 101
0 9 9
2 38 40
4 51 55
98 104
Patient status:
Alive Dead Total
(j
Stage IIA lesions. Johnsson, 4 using the Stockholm technique, had a local recurrence rate of 6% in Stage IB and 14% in Stage IIA at 2 years after treatment. Durrance and associates" reported a central recurrence rate of 1. 9% at M. D. Anderson Hospital in 4 71 patients who had Stage I disease treated by radiotherapy and a rate of 5.6% in patients with Stage II disease. The authors noted an improvement with the advent of megavoltage equipment, a fact also reported by VillaSanta6 and Halpin and associates. 7 In our series, lesion size was relatively unimportant with regard to site of recurrence. Graham and Graham, 8 Piver and Chung, 9 and Van Nagell and associates'0 have shown a relationship between lesion size and the incidence of lymph node metastasis and recurrence. TheM. D. Anderson group 5 also reported problems with central recurrences in patients with large, "barrel-shaped" lesions who were treated radio-
Cervical cancer recurrence after rad1cal hysterectomy 817
Volum< 1:\8 )\:umht'r 7, Part
therapeutically, and they found that the addition of conservative hysterectomy significantly reduced these recurrences. However, in our series, twice as many central recurrences were noted in patients who had lesions of -l ern or less in diameter compared with patients who had lesions greater than -t em in diameter. This finding is not unrt>asonable, because although larger lesions can make the operation more difficult technically, if the primary tumor mass is resected adequately and the extent of dissection is not compromised, central recurrences should not be more frequent when the lesions are larger. The nine patients with "central recurrence alone"
are the ones who are of great concern because they are most likely to signifv technical failure oft he treatment method. Five of these patients had previous irradiation as their primarv treatment, and because of failure of this modality, they underwent operation. or the four nonirradiated patients, none underwent postoperative pehic irradiation. The initial stage o! disease:' in two patients was unknown. three had Stage Ill disease, two had Stage IIA disease, one had Stage I IB dist'ase. and one had Stage lilA disease. The averag-e time until recurrence for these nine patienh was 14 months, with a range of 4 to :W months.
REFERENCES
J., and Symmonds, R. E.: Wertheim hysterectomy: a reappraisal, Obstet. Gynecol. 54:140, 1979. Calame, R. J.: Recurrent carcinoma of the cervix, AM. J. 0BSTET. GYNECOL. 105:380, 1969. Cullhed, S.: Carcinoma cervicis uteri stages I and Ila: treatment-histopathology-prognosis, Acta Obstet. Gyneml. Scand. (Suppl.) 75: I, 1978. Johnsson, J. E.: Squamous cell carcinoma of the uterine cervix. Acta Radio!. (Ther.) (Stockh.) 16:33, 1977. Durrance, F. Y .. Fletcher, G. H., and Rutledge, F. N.: Analysis of central recurrent disease in stages I and II
I. Webb. M.
2. :l.
4.
5.
souantous cell cr~rrinomas nf the cervix on int;:~ct uteru'> Am . .J. Roe~;g~~~X 106;831, 1969. . . .. . ..... '
ti. VillaSanta, U.: Radium and external irradiation versus radiun1 and operation for early invasive carcinon1a of the
uterine cervix. AM.
J.
0BSTET. GYNECOL. 106:498, 1970.
7. Halpin, T. F., Frick, H. C .. II, and Munnell. E. W.: Critical points of failure in the therapy of canfer of the cervix: A reappraisal, AM . .J. OBSTET. GYNECOL. 114:755, 1972. 8. Graham, J. B., and Graham, R. M.: The sensitization response in patients with cancer of the uterine cervix, Cancer 13:5, 1960. 9. Piver, M.S., and Chung, W. S.: Prognostic significance of cervical lesion size and pelvic node metast;tses in cervical carcinoma, Obstet. Gynecol. 46:507, 1975. 10. Van Nagell, J. R., Jr., Donaldson, E. S., Parker, J. C .. van Dyke, A. H., and Wood, E. G.: The prognostic significance of cell tvoe and lesion size in oatients with cervical cancer treat~d by radical mrger;. (~meml. On col. 5:142. 1977.