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Five-year cure rate for carcinoma of the cervix uteri
Five-year cure rate for carcinoma of the cervix uteri With special reference to the comparISon of surgical and radiation therapy
KAZFMASA MASUB1:CHI. M.D . YOSHIO
TE~JI~,
M.D.
HISAMITSU KCBO, M . D. MITSl;O KIM1:RA , M . D . Tok yo, Japan A total of 2,145 cases of cancer of the uterine cervix lure treated by operation or radiation during the 10 years fron! 1950 to 1959 at the Cancer Institute Hospital in Tokyo, and over-all the 5 year cure rate was 59.6 per ce nt. In this study the compariso ns of surgical and radiation treatment in Stages I and II were made. Th e 5 year cu re rate obtained was 90.5 per cent in Stage I and 74.4 per cent in Stage II by opera tion and 88.2 per cent in Stage I and 68.7 per cent i1l Stage II by radiation, but there is no statistical significance between two types of treatment . Also, posttherapeu tic sequelae and clinical tests were st udied on th e W'o types of therapy. The choice of treatment as a principal method was discussed from these results.
the method of treatment. A s(,arch of the literature has failed to reveal any studies where the two methods have been compared in these respects. The method of treatlllent in our hospital has been relatively evenly divided between operation and irradiation, which has afforded liS the opportunity to COlllpare the two methods. A follow-up study was lnade of 2.145 patients who were treated in the 10 v('ar period from 1950 to 1959, and the .') year results, sequelae, and clinical laboratory c1ata in those op('rated upon and those irradiated in Stages I and II were compared.
Q t: EST I 0 " of "vlwther surgery or radiotherapy should be selected as the principal method of treatment for carcinolJla of the cervix uteri has be(~n a controversial issue for a long time and still remains unsolved. ~ ' If), ' " In the Cnited States and European countries the method of choice is generally radiation therapy, hut in Japan operation is usually performed in Stage I and II cases, and the resuits have been as good if no t better than those achieved with irradiation. Th(~ choice of operation or radiotherapy, of cours!', should he based on the superiority of one over the other in the long-term results, but otlwr factors that must be taken into consideration are posttreatment sequelae and any clinical abnormalities associated with THE
Methods and results of treatment
It is fortunate that there are two effective methods of treating cancer of the cervix. Okabayashi-Ogino's extended hysterectomy " and postoperative irradiation were performed in all operative cases. Radiotherapy consisted of radium trea tment with external roentgen therapy but, since 1957, 1,000 c. Telecobal t has b('en used instead of x-ray therapy. For
From the Department of Gynecology, Cancer Institute Hospital, Ni.
566
Volume 103 ~umber
Five-year cure rate for cervical cancer
4
intracavitary radium application, colpostat and tandem were used at the same time. Colpostat consisted of five tubes of 10 mg. and tandem of two tubes of 20 mg. inserted for 2:1 hours at intervals of 5 to 10 days, three times. The total dose was 6,210 mg. hours. The parametrial dose of external x-ray therapy was about 1,500 r, and 1,000 curie Telecobalt radiation was given up to the Illaximum of 2.000 to 4,000 r. There were 2,147 cases during 10 years from 1950 to 1959 in all stages from I to IV, and 2,145 cases were treated, but 2 cases of Stage IV were not treated. The 5 year absolute cure rate was 59.6 per cent. The 5 year cure rate in 448 cases in Stage I was 89.7 per cent, in 716 cases in Stage II 70.8 per cent, in 794 cases in Stage III 43.1 per cent, and in 187 cases in Stage IV 14.8 per cent (Table I). Regarding the 5 year cure rate in operative and irradiated Stage I and II cases, the 5 year cure rate following operation was 90.5 per cent in Stage I and 74.4 per cent in Stage II, but following radiotherapy the rates were 88.2 and 68.7 per cent, respectively. Though it seems rates arc slightly better after operation. statistical analysis revealed no significance (Table II).
Table I. Carcinoma of the cervix uteri (1950-1959) 5 year absolute cure rate - . - - - . ---- . _ - - - - - - - - - - - - - - Five-),ear cure No. of I Star
--N~~--I---%----
patients
I
448 716 794 189*
II
III IV I-IV
2,147
402 507 342 28
89.7 70.8 43.1 14.8
1,279
59.6
------ ._----'----------
*T\,·o cast's were not trcatpd.
-------
....
.
-.-~.--.
Operation
Radiation
I
Five-),ear No. of ___ cure StaRe patients, No. ! % I II
296 266
268 198
90.5 74.4
No. of
Five-),ear cure
Ipatients No. 152 450
134 309
I
Table III. Incidence'of lymph node metastases (1950-1959) No. of patients
% 88.2 68.7
Positive node No_
% 296 4.7 14 266 59 22.2 - - - - .----.---.---StaRe I II
Table IV. Five-year cure rate in patients with and without lymph node metastasis ------~---
Stage
No. of patients
Metastasis I II
14 59
--
%
--
8 30
57.1 50.8
260 168
92.2 81.2
No metastasis
1
II
282 207
- - --.--
-_.- - - - - - -..•...
Table V. Comparison of sequelae in treated patients following operation or radiotherapy during 1950-1959 SurRery (%)
Radiation
Present ph)'sical condition Excellent Fair Poor
93.5 6.2 0.3
90.6 7.7 1.7
Mental attitude Worrying about recurrence Xever worry
5_8 94.2
5A 94.6
(%)
Period required for recover), after treatment Up to 1 year 14.5 12.4 2 years 9.7 11.3 3 years 24.2 17.7 5 years 14.9 14_5 Over 5 years 36_7 44.1 Urinary complication Symptom-free C0mplaints Pollakiuria Dysuria Hematuria Micturition pain
Table II. Five-year cure rates following operation and radiation
567
I ntestinal complication Symptom-free Complaints Constipation Rectal bleeding Loose bowels
52.9 47.1 23.5 29.3 0.3 0.6
765 23.5 19_6 2_1 2_1 0
36.1 63.9 63A
7L8 28.2 20_3 5.5 4_7
1.7
2.0
568 Mosubuchi et 01.
Am.
FdHuary 15. 1969 Obs!. & (;yne< .
J.
Table VIA. Answer from patients about present sexual life
Surgery (188 cases) Inca pable Capable
(%)
12.0 ( 1)
(5)
(2 1)
9l.3
74.6 (58) 36.2 34.5 29.3
88.0 ( 18)
No complaints T emporary complaints Complaints continued Radiation (138 cases) Incapable Capable ~ o complaints T emporary complaints Complaints continued
62 .5 25.0 12.5
43.4 15.1
50.0 ( 1) 100
86.0
(43)
58.1 1B.6
23.3
Radiation, 24 cases
37.9 22.4 27.6
37.5 25.0
12.1
(5:'1) 41.5
25.4
14.0 ( 7)
Surgery, 56 cases
(%)
complaints Temporary complaints Shortening of vagina Others
~o
8.7
•
(%)
50.0 (1 )
Table VIB. Answer from husbands about sexual complaint - - - - -- .. - .. .. ..._---.----
_
Age group (yr.) 40 .. '-' ~-'-5-0'-- 'T
30 ( %)
(%) 25.0
12.5
Lymph node metastases were found in 4.7 per cent Stage I and in 22.2 per cent Stage II cases. The 5 year cure rate with positive nodes was 57.1 per cent in Stage I and 50.8 per cent in Stage II, but the cure rate with negative nodes was 92.2 per cent in Stage I and 81 .2 per cent in Stage II (Tables III and IV). Comparison of sequelae
As it is important in the evaluation of two methods to know whether the patients were free of any sequelae or if they still suffered from complications after 5 years, the presence or absence of sequelae in the operated and irradiated cases was investigated and compared. A total number of 527 patients, consisting
!
60 (%)
Total (%)
51.3 (22 )
( 19 )
48.7 (20)
55.0 2.'>.ll 20.0
21.5
(9)
78.5
26.6 7:l.·t ( 139) 'f~A
3.'>.9 2 1. i 16.9
(23) B:U
(3:{ )
{ 115 ::
63.6
62.6 14.B
18. 2 18.2
22.6
of 293 operative and 234 irradiated cases, were interviewed or questioned by correspondence (Table V). The first question concerning their physical condition at present was answered as "excellent" in 93.5 per cent of the operative cases and in 90.6 per cent of the irradiated cases. The second question was if they worried about rp.currence of carcinoma. A negative answer was given in 94.2 per cent of the operative cases and in 94.6 per cent of the irradiated cases. This mental attitude would seem to indicate that after 5 years without recurrence the patients felt that they had been completely cured. The third question was on the time required to regain their normal health. In the operative group, 48.4 per cent answered "up to 3 years" and 63.3 per cent replied "up to S years." In the radiation group the figures were 41.4 and 55.9 per cent, respectively. Urinary complications occurred in 47.1 per cent of the cases following operation and in 23.5 per cent following irradiation. The disorders were pollakiuria in 23.5 per cent and dysuria in 29.3 per cent after operation. Following irradiation, 19.6 per cent had pol -
Volume 103 :\"llmbel'4
lakiuria, 2.1 per cent dysuria, and 2.1 per cent hematuria. Intestinal complications occurred in 63.9 per cent of the cases following operation and in 28.2 per cent following irradiation. As for intestinal complication, constipation was the most troublesome (63.4 per cent) in the operative group and rectal bleeding was the most frequent complaint (20.3 per cent) after irradiation. Inquiry into the sexual life of the cases following treatment revealed that 73.4 per cent of the operative patients and 83.3 per cent of the irradiated patients enjoyed normal sexual relationship, although 35.9 and 14.8 per cent of the patients, respectively, experienced temporary impairment of sexual functions following treatment. Impotency or impairment was reported by 21.7 per cent of the operative patients and by 22.6 per cent of the irradiated patients. The questionnaire also included the views of the husbands. About 38 per cent reported no difTerence after treatment and about 25 per cent temporary impairment but no trouble at present. Shortening of the vagina was reported by about 25 per cent of the husbands (Tables VIA and VIB). This survey showed a significant difTerence in each of the sequelae and especially significant differences were noted between the two types of treatment in urinary and intestinal complications. Comparison of clinical examination
a clinical study was carried out on 98 cases selected at random, 51 operative and 17 irradiated cases Complete blood cell counts. Red blood cell counts of over 3,500,000 per cubic millimeter were found in 95 per cent of all cases. \Vhite blood cell counts were within normal limits, but slightly lower following irradiation. Hemoglobin values above 70 per cent were found in over 90 per cent of the cases and hematocrit values were interpreted as normal in over 95 per cent. Reticulum cell counts were below normal in 30 per cent of all cases, but no difference was noted between the two methods of treatment. ~ext,
Five-year cure rate for cervical cancer
569
Platelet counts were within normal limits in 73 per cent following operation and in 45 per cent after irradiation, indicating an increase of thrombocytopenia in the latter cases. Bleeding and coagulation times were considered normal. Blood chemistry. Serum protein levels were within normal limits. The albuminglobulin ratio tended to be low, but without pathologic significance. Liver function tests disclosed high icterus index values in 10 per cent following operation and in 4 per cent following irradiation. Cholesterol cephalin flocculation and thymol turbidity tests were interpreted as almost normal. Vrea nitrogen levels were slightly higher in 4 per cent following operation and in 16 per cent following radiation, but no patient was suspected of having uremia. Blood sedimentation rate. A value of within 30 mm. per hour was found in 80 per cent following operation and in 70 per cent following irradiation. Slightly higher values were found in the latter cases. Urinalysis. Cystitis occurred in 12 per cellt after operation and in 14 per cent after irradiation. Microscopic and gross hematuria were not found. No albuminuria or glycosuria was observed. On the basis of these laboratory findings, the patients who survived for over 5 years after treatment were found to have recovered completely and no difference between operation and radiation was observed. Comment
The principal method of treatment for cancer of the cervix is operation or radiation and, as yet, chemotherapy is only employed as an adjuvant remedy. At the present time better therapeutic results arc attained with operative treatment in Japan,14 whereas more effective results arc achieved with radiotherapy in western countries. 3 • 5 The chief reason for this difference probably lies in the approach t9 the therapeutic management of these patients. In western countries the trend in treatment of carcinoma of the cervix is traditionally toward radiation, while in Japan operative treatment has gained
570
Masubuchi et al.
widespread popularity with the introduction of Okabayashi's operation and subsequent modification and improvement of the surgical techniques by later investigators. Therefore, most operable cases are treated by op(~ration and only those inoperable cases are referred for radiation therapy. In addition, many places lack adequate radiation facilities for financial reasons. Of course, the selection of operation or irradiation in anyone hospital should be based on the follOW-lip results of these methods in that hospital; but, fundamentally, the most rational selection would be decided by random selection of the method in a series of patients and comparison of the long-term results. Twombly and Taylor '3 randomly assigned Stage I and II cases to radiation or radical hysterectomy and regional lymphadenectomy plus preoperative and postoperative radiation. Forty-three patients were assigned to operation, but in H of them, operation was not carried out because of their poor general condition, and radiotherapy was used instead. There were ·14 assigned to radiation. The 5 year cure rate for operative group was 58 per cent (25 of 43) and 70 per cent (:H of 44: for the radiation group. Similar results were obtained by Newton.'; ~o study comparable to the above has been reported in Japan and, in the strict sense, the patients in our hospital had not been randomly selected for the type of treatment, but operation and radiotherapy were employed in about equal numbers of Stage I and Stage II cases. Ratio of operative treatment to radiotherapy. Within a 10 year period from 1950 to 1959. operation was performed in 296 (66 per cent) and radiation was given to 152 (:14 per cent) of 'H8 Stage I cases. Of 716 Stage II cases, 266 (37 per cent) had operation and 450 (63 per cent) were treated by radiation. Thus, in a total of ],161 Stage I and Stage II cases. 49 per cent W('fe treated by operation and 51 per cent by irradiation. The ratio of surgery to radiation in Japan during- a 7 year period from 1953 to 1959 in 114 hospitals, according to the report by
February 15 IYh9 Am. ]. Obst. & GyIlt~(".
the Committee on Uterine Cancer in Japan,' was 86.2 }}('r cent to 1;1.8 per ccnt in 1/-,1-90 Stage I cases and 73.1 per CCllt to 26.9 per cent in 7,962 Stage II cases. Also, tl11'l"(' i~ almost no change in the ra tin of tlw 1wo methods according to the recent report bv this Committee" (1964), the ratio being 87. 1 per cent to 12.9 per cent ill 1..166 Stag-e I cases and 77.6 per cent to 22.4 per c{'nt in 2.265 Stage II cases (Table VIIA and VIIB). According to the Annual Report ' in which over 1,000 cases were treated in d('\,(,1l European hospitals during a 5 year period from 1955 to 1959, operation was perfornwd in 29.5 per cent (1,256 cases! and radiation was g-iven in 70.5 per cent (;{,005 cas('s' in J..26 1 Stage I cases and operation in t:Ll per cent (1,084 cases \ and radiation in 86.7 per cent (7,052 cases) in 8.136 Stage II cases (Tables VIllA and VII IB ; . Comparison of 5 year curc rates following opcration and radiation. The 5 year CIll(' rates from cancer of the CCl'vix after operation. as reported in 1965 by the Committee on Cterine Cancer in Japan. \\-Tre 80.6 per cent for Stage I cases and 6+.1 per Cf~lJ t for Stage II cases. After radiotherapy the rates were 53.5 and 45.4 per cent. respectively Tables VIlA and VIIBi. In European countries. according to tlw Annual Report. the 5 year cllre rates aftn operation were 76.6 jwr cent for Stage I and 61.0 per cent for Stage II cases. After radiotherapy. the rates were 7:).2 and 52.8 per cent. respectively ,Tables VIllA atId
VIIIB: . In this comparison of the rt'sults in .Japan and Europe, the cure rate aftn surgical treatment in Japan is better. while hettc! results with irradiation are obtained in Europf,an countrif's. The CUrl' rates obtained at Cancer Institute Hospital in Tokyo are 90.5 per cent in Stage I and 71.·1 per cent in Stage II after operation and 88.2 per cent in Stage I and 68.7 per cent in Stage II aftl'r irradiation. These figures are said to 1)(' ('x('['ptionally good. Lymph node metastasis and prognosis. Many investigators" han' re)Jotted the inc i-
Five-year cure rate for cervical cancer
Volumo 103 :\umber 4
Table VIlA. Ratio of operation to radiation therapy in Japan
Table VIllA. Ratio of operation to radiation therapy i n western countries ( 1953-1957 ) * -_..... _._... __... -- -
Opera tion S ta ge 195:, -1 959' 3,869 I II 5,822
86.2 73.1
621 2,140
13.8 26.9
4,490 7,962
1,364 1,758
8 7.1 77.6
202 507
12.9 22.4
1,566 2,265
._.. _-_._. . _ - - - - - - - - - _•... _ -
571
Stage
No.
I II
1,256 1,084
I
Radiation
% 29.5 13.3
No.
3,005 7,052
% 70.5 86.7
T otal N o.
4,261 8,136
*Taken from The Annual Report, vol. XIII ,' of cleve n hospitals with over 1,000 treated cases. ~amcs of the hospitals: hospital, wi th mostly surgical cases : kna and Jluchafl·g( ; hospitals with equal numbe l" of surg1(:al a nd irrad iated caSt~s : Leipzig and Zagreh; hospitals with mostly irradiated caS l~S: Coptmhagcn, Munich, Oslo, and Wa rsa\,.:; hospitab wit h only irradiat£'d ('.a:-o ('s: Gliwicc, Stockholm , and Manchcst("r .
Table VIlB. Fivc-ycar cure rates following operation and radiation
Surgery
I II
3,869 5,822
3,11 7 3,731
80.6 64.1
Radiation
I II
621 2,140
382 972
53.5 45.4 .~
..
- --
Table VIIlB. Five-year cure rates following operation and radiation*
i
Stage
cure T rea t e d _ _ Five-year _ ._. cases No . ' %
Surgery
I II
1,256 1,084
962 661
76.6 61.0
Radiation
I II
3,005 2,140
2, 199 3,721
78.2 .'i :! .8
*See footnote Table VIllA.
dence of lymph nodc metastasis from carcinoma of the uterine cervix, which, howcver, differs widely from 8.49 per cent (Antoine ) 10 39.9 per ccnt ( Mitani ) with an average of 18.79 per cent for Stage I cancer and from 22 per cent (Parson ) to 43.8 per ccnt ( Lange ) with an average of 33.26 per cent for Stage II. Low rates of 4.7 per cent for Stage I and 22.2 per cent for Stage II were obtained in our series of cases. It is obvious that th(~ 5 ycar cures in cases of positive J1(xles show extremely low rates a nd the rates reported by various investigators rangc from 20 per rent ( Bnmschwig and Rossler ) to 49.2 per cent (Curie ) . The rates in our cases of no metastasis were 92.2 pcr cCllt in Stage T and 81.2 per cent in Stage II cases. In those of positive nodes, the 5 year curc rates wcrc 57.1 per cent in Stage I and 50.8 per cent in Stage II cascs. The cure of over one half of those with positivc nodcs would indicatc thc value of complcte disscction of the pelvic nodes. Comparison of sequelae and clinical reports. Sequelae in patients surviving over 5 vears after opt'ration or radiation therapy
were examined in a total of 527 cases (293 cases of operation and 234 cases of radiotherapy ) among patients who had carcinoma of the uterine cervix, Stage I and II. No marked difference was found between operation a nd radiation groups. Clinical reports were examined in a total of 98 cases, 51 operative cases and 47 radiotherapy cases, among patients with Stage I and Stage II disease. There was no significant differenC!~ between opcration and radiation cases, and no marked changes were noted in test results. Indication and limitation of operation and radiotherapy. In Stage I an d Stage II cancer of the uterine cervix, either operatioll or radiotherapy is indicated. Not all cases, however, arc amenable to surgical treatment. For example, patients may have complications that contraindicatc operation, or the poor condition of the paticnt, hypcrtension . advanced age, obesity, or invasion b(~yond the upper third of the vagina would make surgical treatment unfeasible. Almost a ll the cases may lw considered
572 Mosubuchi et 01.
suited to radiotherapy, but there are some limitations to this method, such as in those indicated below. Radiosensibility. In order to know the sensitivity of an individual to radiation before beginning the treatment, many methods have been tried, but there is none that would give the correct clinical evaluation. If the eITect of radiation therapy appears small, operation should be considered without hesitation. Lymph node metastasis. In the cases studied, both in Stage I and II, about a half of the patients with lymph node metastasis showed survival of 5 years. From such data, operation would seem to be a better method unless there is definitc proof that lymph node metastasis would be cured completely by radiation. Adenocarcinoma o{ th e cervix uteri. In paticnts with mixed type of adcnocarcinoma and epidermoid carcinoma, 5 year survival by radiation is not bad. In cases of purc adenocarcinoma, thc rcsult obtained by radiation is comparatively poor, and well-differenti a ted adenocarcinoma usually does not respond to radiotherapy. Operation would bc indicated, if possible. Pyometra, adnexitis, and fever cases due to putrefa ction of th e original focus . Operation is indicated for all thcse cases. In case operation is impossible, treatment of inflammation should be followed by radiation therapy, beginning with external irradiation. Cancer during pregnancy. Tn the early half of pregnancy, operation gave results com-
REFERENCES
1. Kollmeicr, II. L.: Annual Report on the Results of Treatment in Carcinoma of the uterus and Vagina, Stockholm, 1963, Radiumhemmet, vol. XIII. 2. Burscke, F., and Cantril, S. T.: West. J. Surg. 55: 152, 1947. 3. Cantril, S. T.: Radiation Therapy in the Management of Cancer of the Uterine Cervix, Springfield, Illinois, 1950, Charles C Thomas, Publisher. 4. Graham, J. E., Sotto, L . S. J. , and Paloucek, F. P.: Carcinoma of the Cervix, Philadelphia, 1962, W . B. Saunders Company. 5. Kottmeier, H. L.: Acta obst. et gynec. scandinav. 41: 195, 1962 .
f\'bruary !;i, 1%9 Am. J. Obsl. & (;ynec .
parable to thosc in nonpregnant patients but radiation therapy would be somewhat complicated. If the patient fears residual presell c(: of uterus, operation is, of cours/', indicated. In the final analysis of the advantages a nd disadvantages of the two types of treatment, one mllst take into accoullt the fact that acquisition of surgical skill, especially for opera tions sllch as radical hysterectom y, requires long years of trainillg, a nd each operation must necessarily be complete and thorough. In contrast, a relatively short period of training is all that is needed to learn the essential techniques of radiotherapy, and large numbers of paticllts ca n be treated with this method. III vi(~w of tlie advantages of the latter method. still greater advances in the use of radiotherapy a ('( ~ anticipated . Radiotherapy, however, is not without limitations, and operation then brcorncs necessary. Thus, at present, hoth m ethods of treatment are necessary and are mutually interdependent. Conclusion
Both operation and radiation therapy have advantages and disadvantages, and it is difficult to make any conclusion as to which would be better in general. These two methods should be selected for each individual case according to the surgical trchnique OIl hand, radiation facilities available, and conditions a nd wishes of the patient concerned.
6. Masubuchi, K ., et al.: Cure Rate of Carcinoma of the Cervix Uteri at Cancer Institute Hospital in Tokyo, with Special Reference on the Comparison of Surgical and Radiation Therapy, Ninth International Cancer Congress, Tokyo, 1966. (Abst. 582.) 7. Nippon Shikyugan Iinkai Kaiho (The Report of Japanese Committee on Uterine Cancer): J. Jap. Obst. & Gynec. Soc. 17: 925, 1965. 8. Nippon Shikyugan linkai Nenpo ~o. 7 (The Seventh Annual Report of Japanese Committee on Uterinc Cancer ) : J. Jap. Obst. & Gynec. Soc. 8: 219, 1965. 9. Okabayashi, H.: Surg. Gynec. & Obst. 33: :135, 1921.
Volume 103 :"umber 4
10. Proceeding of the Fourth Congress of the Japan Society for Cancer Therapy (1966, Osaka): J. Jap. Cancer Therapy 2: 39, 1967. 11. Rciffenstuhl, G.: Das Lymphknotenproblem bcim Carcinoma Colli uteri und die Lymphirradiatio pelvis, Miinchen-Berlin-Wien, 1967, Urban & Schwarzenberg.
Five-year cure rate for cervical cancer
573
12. Richards, G. E.: Am. J. Rocntgenol. 58: 783, 1947. 13. TWGlmbly, G. H., and Taylor, H. C., Jr.: Am. J. Roentgenol. 71: 501, 1954. 14. Vagi, H.: West. J. Surg. 70: 241, 1962.
KAZFMASA MASUB1:CHI. M.D . YOSHIO
TE~JI~,
M.D.
HISAMITSU KCBO, M . D. MITSl;O KIM1:RA , M . D . Tok yo, Japan A total of 2,145 cases of cancer of the uterine cervix lure treated by operation or radiation during the 10 years fron! 1950 to 1959 at the Cancer Institute Hospital in Tokyo, and over-all the 5 year cure rate was 59.6 per ce nt. In this study the compariso ns of surgical and radiation treatment in Stages I and II were made. Th e 5 year cu re rate obtained was 90.5 per cent in Stage I and 74.4 per cent in Stage II by opera tion and 88.2 per cent in Stage I and 68.7 per cent i1l Stage II by radiation, but there is no statistical significance between two types of treatment . Also, posttherapeu tic sequelae and clinical tests were st udied on th e W'o types of therapy. The choice of treatment as a principal method was discussed from these results.
the method of treatment. A s(,arch of the literature has failed to reveal any studies where the two methods have been compared in these respects. The method of treatlllent in our hospital has been relatively evenly divided between operation and irradiation, which has afforded liS the opportunity to COlllpare the two methods. A follow-up study was lnade of 2.145 patients who were treated in the 10 v('ar period from 1950 to 1959, and the .') year results, sequelae, and clinical laboratory c1ata in those op('rated upon and those irradiated in Stages I and II were compared.
Q t: EST I 0 " of "vlwther surgery or radiotherapy should be selected as the principal method of treatment for carcinolJla of the cervix uteri has be(~n a controversial issue for a long time and still remains unsolved. ~ ' If), ' " In the Cnited States and European countries the method of choice is generally radiation therapy, hut in Japan operation is usually performed in Stage I and II cases, and the resuits have been as good if no t better than those achieved with irradiation. Th(~ choice of operation or radiotherapy, of cours!', should he based on the superiority of one over the other in the long-term results, but otlwr factors that must be taken into consideration are posttreatment sequelae and any clinical abnormalities associated with THE
Methods and results of treatment
It is fortunate that there are two effective methods of treating cancer of the cervix. Okabayashi-Ogino's extended hysterectomy " and postoperative irradiation were performed in all operative cases. Radiotherapy consisted of radium trea tment with external roentgen therapy but, since 1957, 1,000 c. Telecobal t has b('en used instead of x-ray therapy. For
From the Department of Gynecology, Cancer Institute Hospital, Ni.
566
Volume 103 ~umber
Five-year cure rate for cervical cancer
4
intracavitary radium application, colpostat and tandem were used at the same time. Colpostat consisted of five tubes of 10 mg. and tandem of two tubes of 20 mg. inserted for 2:1 hours at intervals of 5 to 10 days, three times. The total dose was 6,210 mg. hours. The parametrial dose of external x-ray therapy was about 1,500 r, and 1,000 curie Telecobalt radiation was given up to the Illaximum of 2.000 to 4,000 r. There were 2,147 cases during 10 years from 1950 to 1959 in all stages from I to IV, and 2,145 cases were treated, but 2 cases of Stage IV were not treated. The 5 year absolute cure rate was 59.6 per cent. The 5 year cure rate in 448 cases in Stage I was 89.7 per cent, in 716 cases in Stage II 70.8 per cent, in 794 cases in Stage III 43.1 per cent, and in 187 cases in Stage IV 14.8 per cent (Table I). Regarding the 5 year cure rate in operative and irradiated Stage I and II cases, the 5 year cure rate following operation was 90.5 per cent in Stage I and 74.4 per cent in Stage II, but following radiotherapy the rates were 88.2 and 68.7 per cent, respectively. Though it seems rates arc slightly better after operation. statistical analysis revealed no significance (Table II).
Table I. Carcinoma of the cervix uteri (1950-1959) 5 year absolute cure rate - . - - - . ---- . _ - - - - - - - - - - - - - - Five-),ear cure No. of I Star
--N~~--I---%----
patients
I
448 716 794 189*
II
III IV I-IV
2,147
402 507 342 28
89.7 70.8 43.1 14.8
1,279
59.6
------ ._----'----------
*T\,·o cast's were not trcatpd.
-------
....
.
-.-~.--.
Operation
Radiation
I
Five-),ear No. of ___ cure StaRe patients, No. ! % I II
296 266
268 198
90.5 74.4
No. of
Five-),ear cure
Ipatients No. 152 450
134 309
I
Table III. Incidence'of lymph node metastases (1950-1959) No. of patients
% 88.2 68.7
Positive node No_
% 296 4.7 14 266 59 22.2 - - - - .----.---.---StaRe I II
Table IV. Five-year cure rate in patients with and without lymph node metastasis ------~---
Stage
No. of patients
Metastasis I II
14 59
--
%
--
8 30
57.1 50.8
260 168
92.2 81.2
No metastasis
1
II
282 207
- - --.--
-_.- - - - - - -..•...
Table V. Comparison of sequelae in treated patients following operation or radiotherapy during 1950-1959 SurRery (%)
Radiation
Present ph)'sical condition Excellent Fair Poor
93.5 6.2 0.3
90.6 7.7 1.7
Mental attitude Worrying about recurrence Xever worry
5_8 94.2
5A 94.6
(%)
Period required for recover), after treatment Up to 1 year 14.5 12.4 2 years 9.7 11.3 3 years 24.2 17.7 5 years 14.9 14_5 Over 5 years 36_7 44.1 Urinary complication Symptom-free C0mplaints Pollakiuria Dysuria Hematuria Micturition pain
Table II. Five-year cure rates following operation and radiation
567
I ntestinal complication Symptom-free Complaints Constipation Rectal bleeding Loose bowels
52.9 47.1 23.5 29.3 0.3 0.6
765 23.5 19_6 2_1 2_1 0
36.1 63.9 63A
7L8 28.2 20_3 5.5 4_7
1.7
2.0
568 Mosubuchi et 01.
Am.
FdHuary 15. 1969 Obs!. & (;yne< .
J.
Table VIA. Answer from patients about present sexual life
Surgery (188 cases) Inca pable Capable
(%)
12.0 ( 1)
(5)
(2 1)
9l.3
74.6 (58) 36.2 34.5 29.3
88.0 ( 18)
No complaints T emporary complaints Complaints continued Radiation (138 cases) Incapable Capable ~ o complaints T emporary complaints Complaints continued
62 .5 25.0 12.5
43.4 15.1
50.0 ( 1) 100
86.0
(43)
58.1 1B.6
23.3
Radiation, 24 cases
37.9 22.4 27.6
37.5 25.0
12.1
(5:'1) 41.5
25.4
14.0 ( 7)
Surgery, 56 cases
(%)
complaints Temporary complaints Shortening of vagina Others
~o
8.7
•
(%)
50.0 (1 )
Table VIB. Answer from husbands about sexual complaint - - - - -- .. - .. .. ..._---.----
_
Age group (yr.) 40 .. '-' ~-'-5-0'-- 'T
30 ( %)
(%) 25.0
12.5
Lymph node metastases were found in 4.7 per cent Stage I and in 22.2 per cent Stage II cases. The 5 year cure rate with positive nodes was 57.1 per cent in Stage I and 50.8 per cent in Stage II, but the cure rate with negative nodes was 92.2 per cent in Stage I and 81 .2 per cent in Stage II (Tables III and IV). Comparison of sequelae
As it is important in the evaluation of two methods to know whether the patients were free of any sequelae or if they still suffered from complications after 5 years, the presence or absence of sequelae in the operated and irradiated cases was investigated and compared. A total number of 527 patients, consisting
!
60 (%)
Total (%)
51.3 (22 )
( 19 )
48.7 (20)
55.0 2.'>.ll 20.0
21.5
(9)
78.5
26.6 7:l.·t ( 139) 'f~A
3.'>.9 2 1. i 16.9
(23) B:U
(3:{ )
{ 115 ::
63.6
62.6 14.B
18. 2 18.2
22.6
of 293 operative and 234 irradiated cases, were interviewed or questioned by correspondence (Table V). The first question concerning their physical condition at present was answered as "excellent" in 93.5 per cent of the operative cases and in 90.6 per cent of the irradiated cases. The second question was if they worried about rp.currence of carcinoma. A negative answer was given in 94.2 per cent of the operative cases and in 94.6 per cent of the irradiated cases. This mental attitude would seem to indicate that after 5 years without recurrence the patients felt that they had been completely cured. The third question was on the time required to regain their normal health. In the operative group, 48.4 per cent answered "up to 3 years" and 63.3 per cent replied "up to S years." In the radiation group the figures were 41.4 and 55.9 per cent, respectively. Urinary complications occurred in 47.1 per cent of the cases following operation and in 23.5 per cent following irradiation. The disorders were pollakiuria in 23.5 per cent and dysuria in 29.3 per cent after operation. Following irradiation, 19.6 per cent had pol -
Volume 103 :\"llmbel'4
lakiuria, 2.1 per cent dysuria, and 2.1 per cent hematuria. Intestinal complications occurred in 63.9 per cent of the cases following operation and in 28.2 per cent following irradiation. As for intestinal complication, constipation was the most troublesome (63.4 per cent) in the operative group and rectal bleeding was the most frequent complaint (20.3 per cent) after irradiation. Inquiry into the sexual life of the cases following treatment revealed that 73.4 per cent of the operative patients and 83.3 per cent of the irradiated patients enjoyed normal sexual relationship, although 35.9 and 14.8 per cent of the patients, respectively, experienced temporary impairment of sexual functions following treatment. Impotency or impairment was reported by 21.7 per cent of the operative patients and by 22.6 per cent of the irradiated patients. The questionnaire also included the views of the husbands. About 38 per cent reported no difTerence after treatment and about 25 per cent temporary impairment but no trouble at present. Shortening of the vagina was reported by about 25 per cent of the husbands (Tables VIA and VIB). This survey showed a significant difTerence in each of the sequelae and especially significant differences were noted between the two types of treatment in urinary and intestinal complications. Comparison of clinical examination
a clinical study was carried out on 98 cases selected at random, 51 operative and 17 irradiated cases Complete blood cell counts. Red blood cell counts of over 3,500,000 per cubic millimeter were found in 95 per cent of all cases. \Vhite blood cell counts were within normal limits, but slightly lower following irradiation. Hemoglobin values above 70 per cent were found in over 90 per cent of the cases and hematocrit values were interpreted as normal in over 95 per cent. Reticulum cell counts were below normal in 30 per cent of all cases, but no difference was noted between the two methods of treatment. ~ext,
Five-year cure rate for cervical cancer
569
Platelet counts were within normal limits in 73 per cent following operation and in 45 per cent after irradiation, indicating an increase of thrombocytopenia in the latter cases. Bleeding and coagulation times were considered normal. Blood chemistry. Serum protein levels were within normal limits. The albuminglobulin ratio tended to be low, but without pathologic significance. Liver function tests disclosed high icterus index values in 10 per cent following operation and in 4 per cent following irradiation. Cholesterol cephalin flocculation and thymol turbidity tests were interpreted as almost normal. Vrea nitrogen levels were slightly higher in 4 per cent following operation and in 16 per cent following radiation, but no patient was suspected of having uremia. Blood sedimentation rate. A value of within 30 mm. per hour was found in 80 per cent following operation and in 70 per cent following irradiation. Slightly higher values were found in the latter cases. Urinalysis. Cystitis occurred in 12 per cellt after operation and in 14 per cent after irradiation. Microscopic and gross hematuria were not found. No albuminuria or glycosuria was observed. On the basis of these laboratory findings, the patients who survived for over 5 years after treatment were found to have recovered completely and no difference between operation and radiation was observed. Comment
The principal method of treatment for cancer of the cervix is operation or radiation and, as yet, chemotherapy is only employed as an adjuvant remedy. At the present time better therapeutic results arc attained with operative treatment in Japan,14 whereas more effective results arc achieved with radiotherapy in western countries. 3 • 5 The chief reason for this difference probably lies in the approach t9 the therapeutic management of these patients. In western countries the trend in treatment of carcinoma of the cervix is traditionally toward radiation, while in Japan operative treatment has gained
570
Masubuchi et al.
widespread popularity with the introduction of Okabayashi's operation and subsequent modification and improvement of the surgical techniques by later investigators. Therefore, most operable cases are treated by op(~ration and only those inoperable cases are referred for radiation therapy. In addition, many places lack adequate radiation facilities for financial reasons. Of course, the selection of operation or irradiation in anyone hospital should be based on the follOW-lip results of these methods in that hospital; but, fundamentally, the most rational selection would be decided by random selection of the method in a series of patients and comparison of the long-term results. Twombly and Taylor '3 randomly assigned Stage I and II cases to radiation or radical hysterectomy and regional lymphadenectomy plus preoperative and postoperative radiation. Forty-three patients were assigned to operation, but in H of them, operation was not carried out because of their poor general condition, and radiotherapy was used instead. There were ·14 assigned to radiation. The 5 year cure rate for operative group was 58 per cent (25 of 43) and 70 per cent (:H of 44: for the radiation group. Similar results were obtained by Newton.'; ~o study comparable to the above has been reported in Japan and, in the strict sense, the patients in our hospital had not been randomly selected for the type of treatment, but operation and radiotherapy were employed in about equal numbers of Stage I and Stage II cases. Ratio of operative treatment to radiotherapy. Within a 10 year period from 1950 to 1959. operation was performed in 296 (66 per cent) and radiation was given to 152 (:14 per cent) of 'H8 Stage I cases. Of 716 Stage II cases, 266 (37 per cent) had operation and 450 (63 per cent) were treated by radiation. Thus, in a total of ],161 Stage I and Stage II cases. 49 per cent W('fe treated by operation and 51 per cent by irradiation. The ratio of surgery to radiation in Japan during- a 7 year period from 1953 to 1959 in 114 hospitals, according to the report by
February 15 IYh9 Am. ]. Obst. & GyIlt~(".
the Committee on Uterine Cancer in Japan,' was 86.2 }}('r cent to 1;1.8 per ccnt in 1/-,1-90 Stage I cases and 73.1 per CCllt to 26.9 per cent in 7,962 Stage II cases. Also, tl11'l"(' i~ almost no change in the ra tin of tlw 1wo methods according to the recent report bv this Committee" (1964), the ratio being 87. 1 per cent to 12.9 per cent ill 1..166 Stag-e I cases and 77.6 per cent to 22.4 per c{'nt in 2.265 Stage II cases (Table VIIA and VIIB). According to the Annual Report ' in which over 1,000 cases were treated in d('\,(,1l European hospitals during a 5 year period from 1955 to 1959, operation was perfornwd in 29.5 per cent (1,256 cases! and radiation was g-iven in 70.5 per cent (;{,005 cas('s' in J..26 1 Stage I cases and operation in t:Ll per cent (1,084 cases \ and radiation in 86.7 per cent (7,052 cases) in 8.136 Stage II cases (Tables VIllA and VII IB ; . Comparison of 5 year curc rates following opcration and radiation. The 5 year CIll(' rates from cancer of the CCl'vix after operation. as reported in 1965 by the Committee on Cterine Cancer in Japan. \\-Tre 80.6 per cent for Stage I cases and 6+.1 per Cf~lJ t for Stage II cases. After radiotherapy the rates were 53.5 and 45.4 per cent. respectively Tables VIlA and VIIBi. In European countries. according to tlw Annual Report. the 5 year cllre rates aftn operation were 76.6 jwr cent for Stage I and 61.0 per cent for Stage II cases. After radiotherapy. the rates were 7:).2 and 52.8 per cent. respectively ,Tables VIllA atId
VIIIB: . In this comparison of the rt'sults in .Japan and Europe, the cure rate aftn surgical treatment in Japan is better. while hettc! results with irradiation are obtained in Europf,an countrif's. The CUrl' rates obtained at Cancer Institute Hospital in Tokyo are 90.5 per cent in Stage I and 71.·1 per cent in Stage II after operation and 88.2 per cent in Stage I and 68.7 per cent in Stage II aftl'r irradiation. These figures are said to 1)(' ('x('['ptionally good. Lymph node metastasis and prognosis. Many investigators" han' re)Jotted the inc i-
Five-year cure rate for cervical cancer
Volumo 103 :\umber 4
Table VIlA. Ratio of operation to radiation therapy in Japan
Table VIllA. Ratio of operation to radiation therapy i n western countries ( 1953-1957 ) * -_..... _._... __... -- -
Opera tion S ta ge 195:, -1 959' 3,869 I II 5,822
86.2 73.1
621 2,140
13.8 26.9
4,490 7,962
1,364 1,758
8 7.1 77.6
202 507
12.9 22.4
1,566 2,265
._.. _-_._. . _ - - - - - - - - - _•... _ -
571
Stage
No.
I II
1,256 1,084
I
Radiation
% 29.5 13.3
No.
3,005 7,052
% 70.5 86.7
T otal N o.
4,261 8,136
*Taken from The Annual Report, vol. XIII ,' of cleve n hospitals with over 1,000 treated cases. ~amcs of the hospitals: hospital, wi th mostly surgical cases : kna and Jluchafl·g( ; hospitals with equal numbe l" of surg1(:al a nd irrad iated caSt~s : Leipzig and Zagreh; hospitals with mostly irradiated caS l~S: Coptmhagcn, Munich, Oslo, and Wa rsa\,.:; hospitab wit h only irradiat£'d ('.a:-o ('s: Gliwicc, Stockholm , and Manchcst("r .
Table VIlB. Fivc-ycar cure rates following operation and radiation
Surgery
I II
3,869 5,822
3,11 7 3,731
80.6 64.1
Radiation
I II
621 2,140
382 972
53.5 45.4 .~
..
- --
Table VIIlB. Five-year cure rates following operation and radiation*
i
Stage
cure T rea t e d _ _ Five-year _ ._. cases No . ' %
Surgery
I II
1,256 1,084
962 661
76.6 61.0
Radiation
I II
3,005 2,140
2, 199 3,721
78.2 .'i :! .8
*See footnote Table VIllA.
dence of lymph nodc metastasis from carcinoma of the uterine cervix, which, howcver, differs widely from 8.49 per cent (Antoine ) 10 39.9 per ccnt ( Mitani ) with an average of 18.79 per cent for Stage I cancer and from 22 per cent (Parson ) to 43.8 per ccnt ( Lange ) with an average of 33.26 per cent for Stage II. Low rates of 4.7 per cent for Stage I and 22.2 per cent for Stage II were obtained in our series of cases. It is obvious that th(~ 5 ycar cures in cases of positive J1(xles show extremely low rates a nd the rates reported by various investigators rangc from 20 per rent ( Bnmschwig and Rossler ) to 49.2 per cent (Curie ) . The rates in our cases of no metastasis were 92.2 pcr cCllt in Stage T and 81.2 per cent in Stage II cases. In those of positive nodes, the 5 year curc rates wcrc 57.1 per cent in Stage I and 50.8 per cent in Stage II cascs. The cure of over one half of those with positivc nodcs would indicatc thc value of complcte disscction of the pelvic nodes. Comparison of sequelae and clinical reports. Sequelae in patients surviving over 5 vears after opt'ration or radiation therapy
were examined in a total of 527 cases (293 cases of operation and 234 cases of radiotherapy ) among patients who had carcinoma of the uterine cervix, Stage I and II. No marked difference was found between operation a nd radiation groups. Clinical reports were examined in a total of 98 cases, 51 operative cases and 47 radiotherapy cases, among patients with Stage I and Stage II disease. There was no significant differenC!~ between opcration and radiation cases, and no marked changes were noted in test results. Indication and limitation of operation and radiotherapy. In Stage I an d Stage II cancer of the uterine cervix, either operatioll or radiotherapy is indicated. Not all cases, however, arc amenable to surgical treatment. For example, patients may have complications that contraindicatc operation, or the poor condition of the paticnt, hypcrtension . advanced age, obesity, or invasion b(~yond the upper third of the vagina would make surgical treatment unfeasible. Almost a ll the cases may lw considered
572 Mosubuchi et 01.
suited to radiotherapy, but there are some limitations to this method, such as in those indicated below. Radiosensibility. In order to know the sensitivity of an individual to radiation before beginning the treatment, many methods have been tried, but there is none that would give the correct clinical evaluation. If the eITect of radiation therapy appears small, operation should be considered without hesitation. Lymph node metastasis. In the cases studied, both in Stage I and II, about a half of the patients with lymph node metastasis showed survival of 5 years. From such data, operation would seem to be a better method unless there is definitc proof that lymph node metastasis would be cured completely by radiation. Adenocarcinoma o{ th e cervix uteri. In paticnts with mixed type of adcnocarcinoma and epidermoid carcinoma, 5 year survival by radiation is not bad. In cases of purc adenocarcinoma, thc rcsult obtained by radiation is comparatively poor, and well-differenti a ted adenocarcinoma usually does not respond to radiotherapy. Operation would bc indicated, if possible. Pyometra, adnexitis, and fever cases due to putrefa ction of th e original focus . Operation is indicated for all thcse cases. In case operation is impossible, treatment of inflammation should be followed by radiation therapy, beginning with external irradiation. Cancer during pregnancy. Tn the early half of pregnancy, operation gave results com-
REFERENCES
1. Kollmeicr, II. L.: Annual Report on the Results of Treatment in Carcinoma of the uterus and Vagina, Stockholm, 1963, Radiumhemmet, vol. XIII. 2. Burscke, F., and Cantril, S. T.: West. J. Surg. 55: 152, 1947. 3. Cantril, S. T.: Radiation Therapy in the Management of Cancer of the Uterine Cervix, Springfield, Illinois, 1950, Charles C Thomas, Publisher. 4. Graham, J. E., Sotto, L . S. J. , and Paloucek, F. P.: Carcinoma of the Cervix, Philadelphia, 1962, W . B. Saunders Company. 5. Kottmeier, H. L.: Acta obst. et gynec. scandinav. 41: 195, 1962 .
f\'bruary !;i, 1%9 Am. J. Obsl. & (;ynec .
parable to thosc in nonpregnant patients but radiation therapy would be somewhat complicated. If the patient fears residual presell c(: of uterus, operation is, of cours/', indicated. In the final analysis of the advantages a nd disadvantages of the two types of treatment, one mllst take into accoullt the fact that acquisition of surgical skill, especially for opera tions sllch as radical hysterectom y, requires long years of trainillg, a nd each operation must necessarily be complete and thorough. In contrast, a relatively short period of training is all that is needed to learn the essential techniques of radiotherapy, and large numbers of paticllts ca n be treated with this method. III vi(~w of tlie advantages of the latter method. still greater advances in the use of radiotherapy a ('( ~ anticipated . Radiotherapy, however, is not without limitations, and operation then brcorncs necessary. Thus, at present, hoth m ethods of treatment are necessary and are mutually interdependent. Conclusion
Both operation and radiation therapy have advantages and disadvantages, and it is difficult to make any conclusion as to which would be better in general. These two methods should be selected for each individual case according to the surgical trchnique OIl hand, radiation facilities available, and conditions a nd wishes of the patient concerned.
6. Masubuchi, K ., et al.: Cure Rate of Carcinoma of the Cervix Uteri at Cancer Institute Hospital in Tokyo, with Special Reference on the Comparison of Surgical and Radiation Therapy, Ninth International Cancer Congress, Tokyo, 1966. (Abst. 582.) 7. Nippon Shikyugan Iinkai Kaiho (The Report of Japanese Committee on Uterine Cancer): J. Jap. Obst. & Gynec. Soc. 17: 925, 1965. 8. Nippon Shikyugan linkai Nenpo ~o. 7 (The Seventh Annual Report of Japanese Committee on Uterinc Cancer ) : J. Jap. Obst. & Gynec. Soc. 8: 219, 1965. 9. Okabayashi, H.: Surg. Gynec. & Obst. 33: :135, 1921.
Volume 103 :"umber 4
10. Proceeding of the Fourth Congress of the Japan Society for Cancer Therapy (1966, Osaka): J. Jap. Cancer Therapy 2: 39, 1967. 11. Rciffenstuhl, G.: Das Lymphknotenproblem bcim Carcinoma Colli uteri und die Lymphirradiatio pelvis, Miinchen-Berlin-Wien, 1967, Urban & Schwarzenberg.
Five-year cure rate for cervical cancer
573
12. Richards, G. E.: Am. J. Rocntgenol. 58: 783, 1947. 13. TWGlmbly, G. H., and Taylor, H. C., Jr.: Am. J. Roentgenol. 71: 501, 1954. 14. Vagi, H.: West. J. Surg. 70: 241, 1962.