- Email: [email protected]
Cancer of corpus uteri
CANCER OF CORPUS UTERI WILLIAM
P.
HEALY, M.D., F.A.C.S.
Attending Gynecologist, Memorial Hospital NEW YORK, N. Y.
C
ANCER of the corpus or uterine radiation therapy or operation, or a combody has long been regarded as bination of both procedures. From this curable by hysterectomy in the observation it would appear that adenosurgically operable cases. That this view carcinoma of the corpus frequently may is incorrect is amply indicated by the five remain localized to the endometrium for a year end result statistics of various clinics. long time before it invades the myoWe are indebted for this information to metrium or spreads to other parts of the the careful and accurate follow-up systems body through the lymphatics or blood now maintained, often at considerable vessels of the uterus. Histologically cancer of the corpus is a expense, in practically all hospitals. I t has been very disturbing to the gyne- form of adenocarcinoma or so-called glancologist to ascertain that hysterectomy dular cancer, as distinguished from cancer alone rarely gives 40 per cent of five year of the cervix which usually is of the cures in this disease. At the Memorial squamous variety. A limited number of Hospital from 1918 to 1931, inclusive,217 cases of cancer of the corpus occur in cases of cancer of the corpus were under which the histologic structure is composed observation and treatment and 78, or of a mixture of glandular and squamous 36.4 per cent, of these cases are still living tissues, giving rise to a form of tumor for periods varying from five to eighteen growth called adenoacanthoma. Usually years. However, not all of the 139 cases the squamous characteristics in these now dead died from cancer, many succumb- tumors are regarded as instances of squaing to other illnesses due chiefly to or mous metaplasia occurring in glandular associated with advancing years. structures. Very rarely one meets with what hisClinically cancer of the corpus seldom occurs before the fortieth year, and the tologically appears to be a true squamous average age is between fifty-four years and epidermoid cancer arising in and limited to fifty-five years. This age incidence estab- the corpus. A study of the histologic characteristics lishes it as a postmenopausal disease in the majority of cases. This fact is of consider- of the tumor growth in a large series of able importance, as in many instances, cases would indicate that there are two patients are inclined to regard the bleeding major histologic groups of endometrial associated with it as of little consequence adenocarcinoma into which the cases may and to attribute it to a return of the normal be divided. Of these two groups, one, known menstrual cycle. Thus they often delay as adenoma malignum is of lesser histologic seeking medical advice for months. It is malignancy and likewise of lower clinical well known that untreated cases of cancer malignancy than the second group. (Fig. I.) of the cervix rarely live longer than two Histologically the adenoma malign urn years and seldom are curable if symptoms group of cases is characterized by a lawless of the disease have been present for one overgrowth of glands in papillary form or year. On the other hand, many cases of in gland groups or bundles surrounded by cancer of the corpus come under observa- stroma and penetrating into the myotion after symptoms have been present for metrium. This histologic form of penetraone to two years and still are curable by tion is slow and these are the cases that 474
NEW SERIES VOL.
XXXIII,
Healy-Cancer of Corpus Uteri
NO.3
may still be curable despite a history of bleeding for one or more years. In the other group, the adenocarcinoma,
FIG.
I.
there is not only overgrowth and invasion of myometrium by glandular tissues in groups and bundles as in the above cases, but there is destruction of the basement membrane and invasion and infiltration into the stroma and lymphatics of cancer cells individually and in strands, columns and cellular masses. Often indeed there is such an extensive cellular overgrowth that almost all evidence of gland structure is absent. These cases are distinctly more malignant histologically and clinically than those of the first group. Even with a relatively short history, less than six months, they may be incurable because of local and distant metastases. (Fig. 2.) In reviewing our cases in 1930 it seemed to us that our end results were poorest in the group of adenocarcinoma cases treated by hysterectomy without irradiation and
American Journal of Surgery
475
that better results had been obtained in the cases in which irradiation had been combined with hysterectomy or had been used
FIG. 2.
exclusively. In an effort to acquire additional information on this point we have quite uniformly subjected most of our cases of cancer of the corpus to irradiation before the hysterectomy is done. The irradiation, since most of the patients are beyond the menopause consists of a pelvic x-ray therapy cycle of 750 r or 1000 r given to each of four pelvic fields. This is given in daily doses, usually divided, and using a 200 k.v. machine. A week or ten days after completing the x-ray therapy cycle, a diagnostic curettage is done and radium capsules are inserted into the corpus and cervix for an average dose of 3600 milligram hours. If hysterectomy is planned to follow the irradiation it is usually done four to ten weeks later.
476
American Journal of Surgery
Healy-Cancer of Corpus Uteri
SEPTEMBER,
1936
In many instances preliminary deep In the remaining 8 cases preoperative x-ray therapy is omitted and we must irradiation with radium alone or combined depend upon the intrauterine application with x-rays was done. The operative of radium alone for our irradiation results procedure always was complete hysterbecause many of these elderly patients are ectomy with removal of both tubes and not only quite obese but also have a heavy both ovaries and was performed from four pendulous abdomen so that efficient ex- to ten weeks after the irradiation. It is ternal irradiation is impossible. This we quite interesting that the average age of regard as unfortunate for we believe that the 9 cases was fifty-two years which was adequate deep x-ray therapy given before eleven years less than the average age of the curettage and the insertion of radium those in which treatment was limited to offers to the patient greater protection and irradiation. It is reasonable to assume that they were regarded as much better surgical increased hope of cure. In our last five year series there were 3 I risks and therefore the hysterectomy was cases seen in 1930 of which only 22 offered undertaken. Six of the 22 cases in the series are an opportunity for planning a course of treatment with irradiation or surgery. The regarded as dead although one of them, remaining 9 cases were instances of hope- fifty-one years of age, in which panhyslessly advanced recurrent and metastic terectomy without irradiation had been cancer following inadequate irradiation or done for adenoma malignum complicating operation elsewhere and died within a large fibroids, was well and free from few months. Of the 22 cases, 16 or 73 per evidence of disease for three years when cent, are alive. It is interesting that 7 of we lost contact with her. One died in her the 16 living cases were treated by irradia- seventy-first year from cardiac disease two tion therapy only, 4 of these with radium and a half years after radiation therapy. and 3 with radium and x-rays. The young- Another died in her seventy-third year, est of these 7 patients was fifty-seven years also from cardiac disease four: years. after and the oldest seventy-five years, the radiation therapy. The histologic type of average was sixty-three years in this group. carcinoma in these 2 cases was adenoIt is evident that we were dealing with an carcinoma Grade III and Grade IV, respecage group considerably above the average tively. Despite the extremely malignant for cancer of the corpus and in which hys- histologic type of cancer, both patients terectomy would entail grave risk of serious were free from evidence of cancer when complications. No doubt this, to a large they died. A fourth patient treated with radium degree, was a determining factor in the decision to restrict treatment to irradiation and x-rays for papillary adenoma malignum died eight months later following a railroad in these cases. In 9 of the 16 living cases surgery was accident. All evidence of cancer had disthe method of choice. It was combined in appeared. The remaining 2 cases were very every instance but one with irradiation. advanced cases of corpus cancer, sixtyThe single exception was a patient thirty- seven and sixty-eight years old. They were nine years of age with multiple myomata treated with radium and x-rays and lived in which no preliminary curettage was done one and two years, respectively and died as the history and the examination sug- from cancer. Thus it is seen that 3 of the 6 cases were gested only fibromyomata. Panhysterectomy was done and the pathologist's free from evidence of their disease when report on the uterus and tumors was they died, one free from cancer for three adenoma malignum and adenomyoma. years was lost track of and 2 died of cancer. There seems to be a very marked assoThere was no postoperative irradiation ciation of fibromyomata with the incidence given and patient has remained well.
NEW SERIES VOL.
XXXIII,
NO.3
Healy-Cancer of Corpus Uteri
of endometrial cancer. Whether it is more than coincidence is difficult to say since uterine fibromyomata are extremely common and cancer of the corpus is rather infrequent in comparison. However, it seems to me of the utmost importance to do a diagnostic curettage to rule out endometrial cancer in all cases of uterine bleeding associated with fibromyomata when the patients are over forty-five years of age, before resorting to hysterectomy. If the curettage reveals tissue grossly resembling cancer, intrauterine radium and if feasible x-ray therapy should be promptly instituted and the hysterectomy temporarily postponed. In possibly one of every 3 cases treated by irradiation followed four to ten weeks later by hysterectomy, the pathologist will find evidence of persistent cancer in the removed uterus. Often this is said to show marked irradiation changes and to be nonviable. Nevertheless the uncertainty associated with such findings makes it absolutely
American Journal of Surgery
477
essential for us to follow with close observation for at least a year each and every patient in whom treatment for the cancer is limited to irradiation. If uterine discharge or bleeding should again be observed three or four months or longer after radiation treatment, a second diagnostic curettage should be done and if cancer is found intrauterine irradiation should be repeated and, if at all feasible, hysterectomy should follow the second course of radiation treatment. CONCLUSIONS
I t is evident from this discussion that, based upon our experience and observation at the Memorial Hospital in the care of patients suffering from primary cancer of the corpus, the writer believes that adequate radiation therapy alone in the less favorable cases or preliminary to panhysterectomy in the surgically operable cases lways should be the routine procedure.
REFERENCES OF DR. GORDON*
BISSEL, DOUGAL. Surg., Gynec. and Obst., 28: 138, 1919. BONNEY, VICTOR. Jour. Obst. and Gynec. Brit. Emp., 41: 669,1934. BULLARD, E. A. Am. JOlfr. Obst. and Gynec., I I: 623, 1926. FOTHERGILL, W. E. Jour. Obst. and Gynec. Brit. Emp., 38: 251, 1921; New System of Gynaecology, Ed. Thomas Watts Eden and Cuthbert Lockyer, London, Macmillan & Co., Ltd., 1917, Vol. II, p.626. GOFF, BYRON H. Surg., Gynec. and Obst., 57: 7 63, 1933. GoRDON, CHARLES A. Am. Jour. Obst. and Gynec., 29: 547, 1935· GoUGH, ALFRED. Jour. Obst. and Gynec. Brit. Emp., 38: 844, 193 1.
HALBAN. Gynakologische Operationslehre, Berlin and Vienna, Urban und Schwarzenberg, 1932. MACKENRODT, A. Arch. f. Gyniik., 48: 393, 1895. MAlER, F. H. and THUDIUM, W. J. Am. Jour. Obst. and Gynec., 24: 248, 1932. ME STITZ, WALTER. Surg., Gynec. and Obst., 54: 663, 1932• NYULASY, ARTHUR J. Surg., Gynec. and Obst., 33: 53, 1921 . SPALDING, ALFRED B. Am. Jour. Obst. and Gynec., 12: 655, 1926. SHAW, W. FLETCHER. Am. Jour. Obst. and Gynec., 26: 667, 1933; Jour. Obst. and Gynec. Brit. Emp., 41: 853, 1934· * Continued from p. 470.
P.
HEALY, M.D., F.A.C.S.
Attending Gynecologist, Memorial Hospital NEW YORK, N. Y.
C
ANCER of the corpus or uterine radiation therapy or operation, or a combody has long been regarded as bination of both procedures. From this curable by hysterectomy in the observation it would appear that adenosurgically operable cases. That this view carcinoma of the corpus frequently may is incorrect is amply indicated by the five remain localized to the endometrium for a year end result statistics of various clinics. long time before it invades the myoWe are indebted for this information to metrium or spreads to other parts of the the careful and accurate follow-up systems body through the lymphatics or blood now maintained, often at considerable vessels of the uterus. Histologically cancer of the corpus is a expense, in practically all hospitals. I t has been very disturbing to the gyne- form of adenocarcinoma or so-called glancologist to ascertain that hysterectomy dular cancer, as distinguished from cancer alone rarely gives 40 per cent of five year of the cervix which usually is of the cures in this disease. At the Memorial squamous variety. A limited number of Hospital from 1918 to 1931, inclusive,217 cases of cancer of the corpus occur in cases of cancer of the corpus were under which the histologic structure is composed observation and treatment and 78, or of a mixture of glandular and squamous 36.4 per cent, of these cases are still living tissues, giving rise to a form of tumor for periods varying from five to eighteen growth called adenoacanthoma. Usually years. However, not all of the 139 cases the squamous characteristics in these now dead died from cancer, many succumb- tumors are regarded as instances of squaing to other illnesses due chiefly to or mous metaplasia occurring in glandular associated with advancing years. structures. Very rarely one meets with what hisClinically cancer of the corpus seldom occurs before the fortieth year, and the tologically appears to be a true squamous average age is between fifty-four years and epidermoid cancer arising in and limited to fifty-five years. This age incidence estab- the corpus. A study of the histologic characteristics lishes it as a postmenopausal disease in the majority of cases. This fact is of consider- of the tumor growth in a large series of able importance, as in many instances, cases would indicate that there are two patients are inclined to regard the bleeding major histologic groups of endometrial associated with it as of little consequence adenocarcinoma into which the cases may and to attribute it to a return of the normal be divided. Of these two groups, one, known menstrual cycle. Thus they often delay as adenoma malignum is of lesser histologic seeking medical advice for months. It is malignancy and likewise of lower clinical well known that untreated cases of cancer malignancy than the second group. (Fig. I.) of the cervix rarely live longer than two Histologically the adenoma malign urn years and seldom are curable if symptoms group of cases is characterized by a lawless of the disease have been present for one overgrowth of glands in papillary form or year. On the other hand, many cases of in gland groups or bundles surrounded by cancer of the corpus come under observa- stroma and penetrating into the myotion after symptoms have been present for metrium. This histologic form of penetraone to two years and still are curable by tion is slow and these are the cases that 474
NEW SERIES VOL.
XXXIII,
Healy-Cancer of Corpus Uteri
NO.3
may still be curable despite a history of bleeding for one or more years. In the other group, the adenocarcinoma,
FIG.
I.
there is not only overgrowth and invasion of myometrium by glandular tissues in groups and bundles as in the above cases, but there is destruction of the basement membrane and invasion and infiltration into the stroma and lymphatics of cancer cells individually and in strands, columns and cellular masses. Often indeed there is such an extensive cellular overgrowth that almost all evidence of gland structure is absent. These cases are distinctly more malignant histologically and clinically than those of the first group. Even with a relatively short history, less than six months, they may be incurable because of local and distant metastases. (Fig. 2.) In reviewing our cases in 1930 it seemed to us that our end results were poorest in the group of adenocarcinoma cases treated by hysterectomy without irradiation and
American Journal of Surgery
475
that better results had been obtained in the cases in which irradiation had been combined with hysterectomy or had been used
FIG. 2.
exclusively. In an effort to acquire additional information on this point we have quite uniformly subjected most of our cases of cancer of the corpus to irradiation before the hysterectomy is done. The irradiation, since most of the patients are beyond the menopause consists of a pelvic x-ray therapy cycle of 750 r or 1000 r given to each of four pelvic fields. This is given in daily doses, usually divided, and using a 200 k.v. machine. A week or ten days after completing the x-ray therapy cycle, a diagnostic curettage is done and radium capsules are inserted into the corpus and cervix for an average dose of 3600 milligram hours. If hysterectomy is planned to follow the irradiation it is usually done four to ten weeks later.
476
American Journal of Surgery
Healy-Cancer of Corpus Uteri
SEPTEMBER,
1936
In many instances preliminary deep In the remaining 8 cases preoperative x-ray therapy is omitted and we must irradiation with radium alone or combined depend upon the intrauterine application with x-rays was done. The operative of radium alone for our irradiation results procedure always was complete hysterbecause many of these elderly patients are ectomy with removal of both tubes and not only quite obese but also have a heavy both ovaries and was performed from four pendulous abdomen so that efficient ex- to ten weeks after the irradiation. It is ternal irradiation is impossible. This we quite interesting that the average age of regard as unfortunate for we believe that the 9 cases was fifty-two years which was adequate deep x-ray therapy given before eleven years less than the average age of the curettage and the insertion of radium those in which treatment was limited to offers to the patient greater protection and irradiation. It is reasonable to assume that they were regarded as much better surgical increased hope of cure. In our last five year series there were 3 I risks and therefore the hysterectomy was cases seen in 1930 of which only 22 offered undertaken. Six of the 22 cases in the series are an opportunity for planning a course of treatment with irradiation or surgery. The regarded as dead although one of them, remaining 9 cases were instances of hope- fifty-one years of age, in which panhyslessly advanced recurrent and metastic terectomy without irradiation had been cancer following inadequate irradiation or done for adenoma malignum complicating operation elsewhere and died within a large fibroids, was well and free from few months. Of the 22 cases, 16 or 73 per evidence of disease for three years when cent, are alive. It is interesting that 7 of we lost contact with her. One died in her the 16 living cases were treated by irradia- seventy-first year from cardiac disease two tion therapy only, 4 of these with radium and a half years after radiation therapy. and 3 with radium and x-rays. The young- Another died in her seventy-third year, est of these 7 patients was fifty-seven years also from cardiac disease four: years. after and the oldest seventy-five years, the radiation therapy. The histologic type of average was sixty-three years in this group. carcinoma in these 2 cases was adenoIt is evident that we were dealing with an carcinoma Grade III and Grade IV, respecage group considerably above the average tively. Despite the extremely malignant for cancer of the corpus and in which hys- histologic type of cancer, both patients terectomy would entail grave risk of serious were free from evidence of cancer when complications. No doubt this, to a large they died. A fourth patient treated with radium degree, was a determining factor in the decision to restrict treatment to irradiation and x-rays for papillary adenoma malignum died eight months later following a railroad in these cases. In 9 of the 16 living cases surgery was accident. All evidence of cancer had disthe method of choice. It was combined in appeared. The remaining 2 cases were very every instance but one with irradiation. advanced cases of corpus cancer, sixtyThe single exception was a patient thirty- seven and sixty-eight years old. They were nine years of age with multiple myomata treated with radium and x-rays and lived in which no preliminary curettage was done one and two years, respectively and died as the history and the examination sug- from cancer. Thus it is seen that 3 of the 6 cases were gested only fibromyomata. Panhysterectomy was done and the pathologist's free from evidence of their disease when report on the uterus and tumors was they died, one free from cancer for three adenoma malignum and adenomyoma. years was lost track of and 2 died of cancer. There seems to be a very marked assoThere was no postoperative irradiation ciation of fibromyomata with the incidence given and patient has remained well.
NEW SERIES VOL.
XXXIII,
NO.3
Healy-Cancer of Corpus Uteri
of endometrial cancer. Whether it is more than coincidence is difficult to say since uterine fibromyomata are extremely common and cancer of the corpus is rather infrequent in comparison. However, it seems to me of the utmost importance to do a diagnostic curettage to rule out endometrial cancer in all cases of uterine bleeding associated with fibromyomata when the patients are over forty-five years of age, before resorting to hysterectomy. If the curettage reveals tissue grossly resembling cancer, intrauterine radium and if feasible x-ray therapy should be promptly instituted and the hysterectomy temporarily postponed. In possibly one of every 3 cases treated by irradiation followed four to ten weeks later by hysterectomy, the pathologist will find evidence of persistent cancer in the removed uterus. Often this is said to show marked irradiation changes and to be nonviable. Nevertheless the uncertainty associated with such findings makes it absolutely
American Journal of Surgery
477
essential for us to follow with close observation for at least a year each and every patient in whom treatment for the cancer is limited to irradiation. If uterine discharge or bleeding should again be observed three or four months or longer after radiation treatment, a second diagnostic curettage should be done and if cancer is found intrauterine irradiation should be repeated and, if at all feasible, hysterectomy should follow the second course of radiation treatment. CONCLUSIONS
I t is evident from this discussion that, based upon our experience and observation at the Memorial Hospital in the care of patients suffering from primary cancer of the corpus, the writer believes that adequate radiation therapy alone in the less favorable cases or preliminary to panhysterectomy in the surgically operable cases lways should be the routine procedure.
REFERENCES OF DR. GORDON*
BISSEL, DOUGAL. Surg., Gynec. and Obst., 28: 138, 1919. BONNEY, VICTOR. Jour. Obst. and Gynec. Brit. Emp., 41: 669,1934. BULLARD, E. A. Am. JOlfr. Obst. and Gynec., I I: 623, 1926. FOTHERGILL, W. E. Jour. Obst. and Gynec. Brit. Emp., 38: 251, 1921; New System of Gynaecology, Ed. Thomas Watts Eden and Cuthbert Lockyer, London, Macmillan & Co., Ltd., 1917, Vol. II, p.626. GOFF, BYRON H. Surg., Gynec. and Obst., 57: 7 63, 1933. GoRDON, CHARLES A. Am. Jour. Obst. and Gynec., 29: 547, 1935· GoUGH, ALFRED. Jour. Obst. and Gynec. Brit. Emp., 38: 844, 193 1.
HALBAN. Gynakologische Operationslehre, Berlin and Vienna, Urban und Schwarzenberg, 1932. MACKENRODT, A. Arch. f. Gyniik., 48: 393, 1895. MAlER, F. H. and THUDIUM, W. J. Am. Jour. Obst. and Gynec., 24: 248, 1932. ME STITZ, WALTER. Surg., Gynec. and Obst., 54: 663, 1932• NYULASY, ARTHUR J. Surg., Gynec. and Obst., 33: 53, 1921 . SPALDING, ALFRED B. Am. Jour. Obst. and Gynec., 12: 655, 1926. SHAW, W. FLETCHER. Am. Jour. Obst. and Gynec., 26: 667, 1933; Jour. Obst. and Gynec. Brit. Emp., 41: 853, 1934· * Continued from p. 470.