Carcinoma of the Prostate John R. Caulk and S. B. Boon-Itt Am J Cancer 1932;16:1024-1052. Updated version E-mail alerts Reprints and Subscriptions Permissions Access the most recent version of this article at: http://cancerres.aacrjournals.org/content/16/5/1024 Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at [email protected] To request permission to re-use all or part of this article, contact the AACR Publications Department at [email protected] Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE JOHN R. CAULK, M.D., F.A.C.S., St. Louis, Mo., S. B. BOON-ITT, M.D., Bangkok, Siam 1 AND (From the Genilo-Urinary Section of the Department of Surgery, School of Medicine, Washington University, St. Louis) One of the most vital problems confronting the urological surgeon today concerns the early recognition and treatment of cancer of the prostate. Some authors have likened this lesion to a somewhat analogous one occurring in the female breast. In many points they are similar; in many others they are entirely different. Both are essentially diseases of the latter part of middle life. They are similar, also, in their tendency to spread very early by the way of the lymphatic system, in their power to disseminate far and wide, and in their predilection to skeletal metastasis. In neither of these two types of carcinoma is the prognosis as to the duration of life good, and in both the end-results of treatment are still unsatisfactory. Of the two, carcinoma of the prostate appears the more unfavorable. Oertel (1) points out the similarity in the reaction of breast and prostatic tissues and contends that carcinoid hyperplasia in each of these organs is potentially cancerous, although it does not always develop into cancer. Cheatle (2) calls attention to a sequence of events occurring in the prostate similar to that which is observed in certain diseases of the breast. The cystiphorous desquamative epithelial hyperplasia is transformed into epithelial neoplasia, and this latter condition further changes into true cancerous tissue. In one section of a prostate the author observed all of these three stages. According to Mark and McCarthy (3), the first case of carcinoma of the prostate was recognized by Langstaff in 1817. Billroth in 1867 first attempted to treat this condition by surgery. The frequency of the neoplasm was not well recognized until 1900, when Albarran and Halle intimated that it was not uncommon. Since then a number of studies have been made on the subject, various facts have been brought to light, and many helpful sug1 The writers acknowledge with thanks the assistance of Dr. John F. Patton in the preparation of this paper. 1024 Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1025 gestions presented by different investigators. In spite of the numerous studies already made, the management of carcinoma of the prostate is still far from satisfactory. The following study is attempted with the hope of furnishing more data on this still unsolved problem. It comprises 222 cases of prostatic carcinomata seen in the Genito-Urinary Service of the 'Barnes Hospital and in private practice. Four cases were apparently metastatic and are therefore not included in the study. They are discussed under a separate heading (page 1049). INCIDENCE It is well recognized that cancer of the prostate is not uncommon. Hoffman (4) presents data of the New York Pathological Institute, giving 36 deaths from carcinoma of the prostate in 2,641 deaths from cancer of various organs (908 male deaths and 1,733 female deaths). This makes 1.3 deaths for every 100 deaths from cancer in both sexes, or 3.96 deaths for every 100 cancer deaths in males only. According to the mortality statistics (5) of the U. S. Bureau of the Census, there were in 1927 a total of 1,141.9 deaths from all causes per 100,000 population in the registration area of the continental United States; 95.6 deaths per 100,000 population were attributed to cancer and malignant tumors of all kinds, and 3.5 of these were due to carcinoma of the prostate. This means that in about everyone thousand deaths of persons of both sexesin 1927 there were 3.5 deaths from carcinoma of the prostate, or in about every thousand deaths of males, of all ages, 5.6 deaths were attributable to cancer of the prostate. When this is considered in terms of the total deaths-almost 1,237,000 in the year 1927-the toll is far from insignificant. These figures, furthermore, represent only the number of cases definitely known. Without doubt there were many cases not included in the statistics, either because the diagnosis was not apparent, or because the secondary symptoms were so preponderant as to mask the true primary cause. Young (6) states that 5 per cent of the total number of patients admitted to his clinic had carcinoma of the prostate. About 2 per cent of all genito-urinary cases seen by one of the writers (J. R. C.) in private practice were cases of prostatic malignancy. Of 700 cases of obstructive conditions of the prostate seen by Barney and Gilbert (7), 23.9 per cent were due to malignancy. Cunningham (8) found carcinoma of the prostate in 20 per cent 96 Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1026 JOHN R. CAULK AND S. B. BOON-ITT of all cases of prostatic obstruction. Of the 222 cases in the series under consideration in this paper, only 162 were hospital cases. This represents about 19 per cent of all the cases of prostatic obstruction treated in the Barnes Hospital. Correction of precancerous conditions, early recognition of cancer, and prompt therapy are fundamental. Since prostatic inflammation is so ubiquitous and inflammation is in many instances a precursor of cancer, it is quite possible that chronic prostatitis may be instrumental in the creation of a definite proportion of these cases. With this in view, it would seem necessary for the medical profession to devote stricter attention to the inflammatory lesions of the prostate. Our experience seems to indicate a definite association between the two lesions. It has been abundantly demonstrated that about one in every five cases of prostatism is due to cancer, and since approximately 15 per cent of all men beyond fifty suffer from the results of prostatism, it would at least appear that neglected inflammatory lesions may predispose to cancer growth. In hundreds of cases of chronic prostatitis which have been properly cared for we have seen cancer develop in but one or two instances. This view is contrary to the usual conception that prostatic cancer originates in the posterior lobe, or surgical capsule, well away from the site of the usual inflammatory or hyperplastic changes in the gland. Another significant feature which indicates that many prostate cancers may not originate in the posterior capsule is that tissue removed from the internal orifice of the bladder by means of the punch clearly exhibits cancer in 80 per cent of the cases, even though in many instances rectal examination indicated either an early lesion or questionable malignancy. DIAGNOSIS The diagnosis of carcinoma of the prostate in this series was made largely through the process of exclusion, supported by the characteristic feel of the carcinomatous gland on palpation per rectum. The final diagnosis of all cases was made by one of the senior members of the service. Microscopic examination of tissues was made in 107 cases. In 64 cases the tissue was obtained by the punch operation and in 43 by prostatectomy (see Table I). None was taken by the needle of Barringer. In these 107 cases, the microscopic report was positive for carcinoma in 94 cases, in 52 of which the tissue was obtained by the cautery punch. It is of Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1027 CARCINOMA OF THE PROSTATE interest to note that about 80 per cent of tissue removed by the punch histologically proved to be carcinoma, a finding which is not in accord with the assumption that carcinoma of the prostate commonly starts in the posterior capsule. If such were the case, it would have to be assumed that practically the whole gland would be involved before the cancerous tissue could be punched out per urethra. TABLE I Microscopic DiagnoBis of Tissue Removed from Prostate (107 Cases) Poeitive Nee.tin Tissue removed by Caulk's cautery punch (64 cases) ...... 52 cases (81.4 12 cases per cent) Tissue removed by prostatectomy (43 eases).............. 42 C&IIeII (97.6 lease per cent) TOTAL................................ 94 C&IIeII 13 C&IIeII It is well recognized that minute growths of the prostate readily escape detection (Bugbee 11; Hirsch and Schmidt 12). Thus a negative report on tissue examined does not disprove the presence of a carcinoma in the gland. In 2 cases in this series, in which carcinoma was suspected, prostatectomy was done and a microscopic diagnosis of benign hypertrophy was made. A little over a year later, both patients returned with typical carcinomatous masses at the site of the prostate, with metastatic lessions in the bladder. Hunt (28) observed a similar case. It is commonly understood that simple prostatectomy cannot completely remove the prostatic tissue, hence a part or perhaps even the whole of the cancerous growth was left behind in the above cases. This would seem to support the fact that the lesions were confined to the posterior capsule. AGE INCIDENCE Carcinoma of the prostate is essentially a disease of late middle age. Table II gives the distribution by decades of 196 cases in this series. It will be seen that 93.9 per cent of the patients were over fifty years of age. Approximately 90 per cent were in the sixth, seventh, and eighth decades. For the entire series the average age when the patient was first seen was sixty-three years. In Bumpus' series the average was 64.8 years. Barringer's series of 129 cases (14) showed 122 (94.6 per cent) patients above fifty Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1028 JOHN R. CAULK AND B. B. BOON-ITT years of age. Only two of his patients were between thirty and forty. The youngest patient in the writers' series was twenty-five years old. He was admitted complaining of pain in the rectum of six months' duration. Examination revealed carcinoma of the prostate. Death occurred nine days after admission, and postmortem examination revealed carcinoma of the prostate with metastasis to the liver, peritoneum, retroperitoneal glands, and mediastinal glands. The youngest patient reported in the literature was a youth of seventeen (Gardner and Cummins, 15). TABLE II Age Incidence in 196 Cases of Carcinoma of the Prostate 2G--29 years. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3G--39 years.... .. .. .. .. .. .. .. 4Q-49 years , 5G--59 years 6lHi9 years 7G--79 years.. . .. . .. .. .. .. .. . .. .. . . .. .. .. .. 8G--89 years. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1 ca.se (0.5%) 1 ca.se (0.5%) 10 cases (5.1%) 37 cases (18.9%) 75 cases (38.3%) 60 cases (30.6%) 12 cases (6.1%) TOTAL ••••••••••••••••••••••••••••.•••.•• 196 Mean average age of 196 cases Youngest case in the series Oldest case in the series cases (100%) " . . . . . . . . . . . .. 63.4 years " 25 years , . " 85 years SYMPTOMS Cancer of the prostate in itself produces no symptoms, but on account of its proximity to the bladder neck, its increase in size readily gives rise to urinary disturbances. Bumpus (13) reports that in 79 cases of carcinoma of the prostate with metastasis, pain occurred as the first symptom in 34.1 per cent, frequent urination in 27.8 per cent, and difficulty of urination in 16.4 per cent, while in a group of 283 cases without metastasis, the first symptoms were frequency in 36.7 per cent, difficulty in 32.5 per cent, and pain in only 12.01 per cent. Frequency and difficulty in urination were the two most common symptoms in Bumpus' series. Barringer (14) reports that 115 of his series of 145 cases presented urinary disturbances as early symptoms. Barney and Gilbert state that in over 22 per cent of their cases the chief complaints were not referable to the genito-urinary system. Bugbee contends that II the sudden onset of retention in the presence of comparatively mild urinary symptoms may be suggestive of malignancy." The chief complaints in 194 cases in the present series are given Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1029 CARCINOMA OF THE PROSTATE in Table III. It will be observed that 143 of 194 patients, or about 70 per cent, complained of symptoms referable to the genitourinary system. with a mean average of three years' duration. Symptoms of obstruction-ranging from some difficulty in voiding to complete urinary retention-and frequency of urination were the two most common complaints when the patients were first seen. In 42 cases, or 21.65 per cent of the total number, the complaints were not referable to the urinary system but were suggestive of TABLE III Chief Complaint8 as Given by Patient8 When Fir8t Seen, with Average Duration of Complaint Number of caeee COMPLAINTS REFERABLE TO URINABY SYSTEM, CASES (73.71%) Averall" duration of complaint 143 Obstruction to urination (ranging from slight difficulty to retention) . Frequency of urination . "Bladder trouble" . Painful urination . Nocturia , , .. Hematuria . Dribbling . TOTAL. . . . . . . . . . . . . . . . . . . . . . . . . . . .. COMPLAINTS SUGGESTIVE OF EXTENSION OR METABTASIS, 42 CASES (21.65%) Pain in lower back , .. Pain in legs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Weakness and loss of weight.... . . . . . . . . . . . . . . Pain in rectum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gastro-intestinal symptoms. . . . . . . . . . . . . . . . . . Edema of lower extremities.... .. . . .. . . . . . . . . . TOTAL. . . . . • . . . . • . . . . . • • • • • • . • • . . . . SILENT CASES... . . • . . • . .• . . . . . . • • . . • . . . . • • • • . . . 61 (42.6%) 51 (35.6%) 16 (11.2%) 7 (4.9%) 6 (4.3%) 1 1 143 cases 3 yrs, 2 yrs, 3 yrs. 3 yrs. 1 yr. 2 mos. 11 mos. 8 mos. 1 mo. 10 mos. 3 yrs. (average) 14 10 8 4 4 2 42 cases 9 (4.64%) extension of the growth or metastatic processes. Among these complaints, pain in the lower back and in the legs appears to be the most common. Nine patients were admitted with complaints other than those recorded above. In these cases the prostatic growth was found accidentally. One of these nine cases was an accident case, in which examination revealed carcinoma of the prostate with extensive skeletal metastasis. Another patient was admitted to the Medical Service for leukemia i routine physical examination revealed an independent cancer of the prostate, confirmed by the necropsy report. In one case, carcinoma of the Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1030 JOHN R. CAULK AND S. B. BOON-ITT prostate was found co-existing with an independent tumor of the brain. The diagnosis of this last case was confirmed by postmortem examination. These silent cases comprise 4.64 per cent of the total cases in the series. TABLE IV First Symptom as Noted by Patient in 194 Caee« 1. FIRST SYMPTOM REFERABLE TO URINARY SYSTEM Frequent urination Difficulty in urination Painful urination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Nocturia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Hematuria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Retention of urine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Dribbling after micturition. . . . . . . . . . . . . . . . . . . . . . . . . . . .. Urgency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Wea.k stream. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Desire to urinate all the time. . . . . . . . . . . . . . . . . . . . . . . . . . . Incontinence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 caBe8 20 C&8eS 20 cases 22 C&8eS 5 cases 4 caSell 3 cases 2 cases 3 cases 1 case 1 case TOTAL 160 C&ses(82.48%) II. FIRST SYMPTOM SUGGESTIVE OF SPREAD OF MALIGNANCY Pain in lower back. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 C&8e8 Gastro-intestinal symptoms. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 7 C&8e8 Wea.knllll8 and loss of weight 5 casea Pain referable to hip joint. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 5 cases Pain in the legs. • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 2 cases TOTAL III. FIRST SYMPTOM OTHER THAN THOBE OF GROUPS I AND III 26 C&Be8 (13.4%) 8 cases (4.12%) The symptoms of onset are listed in Table IV. The earliest symptoms most commonly observed by the patients in this series were frequency and difficulty of urination. One of the silent cases in Table III gave a history of frequent urination several years prior to the date of admission. In Table V are tabulated the general symptoms of all cases. Here it is to be noted that frequent, painful, and difficult urination are the three most common general symptoms in the series. It is commonly recognized that low backache and sciatica-like pain are fairly common in cases with carcinoma of the prostate. In the present study, pain in the lower back was met with once in every 5 cases, while sciatica-like pain was encountered once in every 6.1 cases. BLOOD PICTURE Piney (16) points out that metastatic lesions in the bone marrow frequently give rise to II pernicious anemia JJ -like changes in the blood. He further summarizes the changes which he believes Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1031 CARCINOMA OF THE PROSTATE to be sufficiently characteristic for the diagnosis of carcinoma of the bone marrow as follows: (1) reduction in the number of red corpuscles: (2) high color index, not always above one; (3) slight leukocytosis; (4) leukocytosis due to increase of polymorphonuclear TABLE V General Symptoms in 194 Cases Given &8 one of the symptoms in Such symptom occurs Frequency of urination ............ " .... " .......... 122 cases lin 1.6 times Painful urination.................................... 100 cases lin 1.9 times Difficulty in urination ............................... 94 cases lin 2.1 times Retention of urine .................................. 70 cases 1 in 2.8 times Urgency ........................................... 50 cases lin 3.9 times Hematuria ......................................... 39 cases lin 5.0 times Dribbling after micturition........................... 41 cases 1 in 4.8 times Nocturia without increase in frequency during day ...... 41 cases 1 in 4.8 times Weak stream ....................................... 16 cases 1 in 12.2 times Difficulty in starting stream .................. ........ 12 cases 1 in 16.2 times Pain referred to lower back ........................... 39 cases lin 5.0 times Pain referred to legs................................. 32 cases lin 6.1 times Pain referred to hip joint............................. 14 cases 1 in 14.0 times Loss of weight ...................................... 70 cases lin 2.8 times neutrophils; (5) anisocytosis, ete., well marked; (6) nucleated red corpuscles present, both normoblasts and megaloblasts: (7) myelocytes and myeloblasts present. In almost every case of cancer a definite degree of anemia is present, but this is not of a specific character. Roberts (17) divides carcinoma of the prostate into three groups: (1) cases in which prostatic symptoms predominate; (2) cases in which pelvic and sacral pain predominate j (3) cases in which distant dissemination of the growth gives rise to symptoms. In the third group he recognizes profound anemia, almost of the perniciousanemia type, as one of the clinical features. In 156 cases of this series blood counts were obtained. The findings are tabulated in Table VI under two headings: cases with skeletal metastasis and cases with metastasis elsewhere than in the osseous system. In the former group the average red cell count and the mean percentage of hemoglobin of the blood were distinctly lower than in the latter. This reduction in red blood cells and hemoglobin percentage could not be accounted for by visible hemorrhage, for, even eliminating the cases with hematuria, the figures remain low. Eight cases with skeletal metastasis showed Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1032 JOHN R. CAULK AND S. B. BOON-ITT the most marked anemia, with an average of 2.9 million red blood cells per cubic millimeter and 50 per cent hemoglobin. It is to be regretted that the data in these cases are not sufficient to permit a study of other blood changes also. The figures for the group with metastasis elsewhere than in the bones are within normal limits. TABLE VI Relation of Blood Change8 to Skeletal M etaBtasiB in 156 CaBe8 of Carcinoma of the Prostaie With skeletal metastasis TOTAL NUMBER OF CASES . . • • . . . . . . . . . . . . . . . . • . . . Average hemoglobin ......................... Average red cell count ....................... Average color index .......................... Average white cell count ..................... NUMBER OF CASES WITHOUT HEMATURIA . . . . . . . . . . . Average hemoglobin ......................... Average red cell count ....................... Average color index .......................... Average white cell count ..................... With other than skeletal metastasis 32 70 per cent 3,550,000 0.98 8,200 56 95 percent 4j350,OOO 1.10 11,700 23 65 per cent 3,310,000 9.98 8,100 44 lOOper cent 4,360,000 1.15 11,800 Metu- tati. leeioDB not found 68 BLOOD-PRESSURE READINGS Blood-pressure readings were recorded in 125 of this series of cases. The normal blood-pressure variation for the different ages was computed by Faught's method. On comparison of the normal computed value for the age with the actual reading of the case, it is found that 26.4 per cent of the 125 cases showed definitely high blood-pressure and 20.0 per cent gave readings below the normal variation. Shaw and Young (19) believe that prostatic hypertrophy does not cause any marked increase in the bloodpressure and support their contention by figures showing that blood-pressure bears no relation to the residual urine of the case. In Table VII cases with urinary disturbances as the chief complaint and cases with high non-protein nitrogen in the blood are grouped according to the blood-pressure readings. The percentages in the high blood-pressure column show a slight rise in cases with urinary disturbances and also in cases with a high non-protein nitrogen content of the blood. The increase is not striking, however, as one would expect if the dysfunction of the genito-urinary apparatus were responsible for the increase in the blood-pressure. From the results of this study, therefore, it would seem that, although Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1033 CARCINOMA OF THE PROSTATE urinary disturbances tend slightly to cause an increase in bloodpressure, one is not justified in concluding that these disturbances are responsible for the hypertension, for the increase here is within the limit of error, the total number of cases being comparatively small. TABLE VII Relation oj Blood-pressure to Urinary Disturbanee« in 1£5 Cose« TD- tal C&ll8II Blood-preeaure reading within normal variation Blood;1?reeaure reading higher than normal variation Blood-preeaure reading lower than normal variation All cases regardless of complaints ........... 125 67 cases (53.6%) 33 cases (26.4%) 25 cases (20.0%) Cases with urinary symptoms as chief complaints............... 90 49 cases (54.4%) 30 cases (33.3%) 11 cases (12.3%) Cases with non-protein nitrogen higher than 50 mgm. per 100 c.c. of 7 cases (33.3 %) 2 cases (9.6%) blood................ 21 12 cases (57.1 %) SIZE OF THE PROSTATE The size of the prostate was recorded in 205 cases: 34 per cent were small, 48 per cent moderate, and only 18 per cent large. Fifty per cent of the prostates in cases with metastases were small, 25 per cent were of moderate size, and 25 per cent large. Bone metastases occurred in 19 per cent, and in the majority of instances were associated with small or moderately enlarged prostates. Eighty per cent of the bone metastases were located in the pelvis and lumbar spine, 10 per cent in the femur, 5 per cent in the ribs, and 5 per cent in the shoulder. There were 7 cases showing direct extension: 3 to the bladder, 1 to the rectum, 1 to the bladder and rectum, and 2 to the urethra. It is generally known that carcinoma of the prostate is of two types, one with a strong tendency to produce early and distant metastasis, the other with a longer course and commonly associated with marked urinary disturbances. The prostate gland in this latter type of carcinoma is frequently found to be enlarged. In the former type the gland is usually of normal size or smaller than normal. CYSTOSCOPIC FINDINGS It is the experience of the Genito-Urinary Service of the Barnes Hospital that the cystoscopic finding of irregularity at the internal orifice is of special importance in carcinoma of the prostate. The intravesical obstruction in cancer of the prostate is usually not as Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1034 JOHN R. CAULK AND S. B. BOON-ITT pronouncedly lobular as in benign conditions, but tends to assume a collar arrangement or contracture and is likely to show irregularities, cystic and bullous changes, and occasionally deposits of fibrin and submucous hemorrhage. An irregular edematous appearance is suggestive of carcinoma. Another important feature is puckering of the bladder mucosa at the sites where the seminal vesicles are in contact with the bladder wall. Submucosal hemorrhages may be observed at the depression, and in later cases small areas of ulceration. This is designated as II neighborhood carcinoma." In 105 cases of this series the cystoscopic findings are available. They are tabulated in Table VIII. About one half of the cases TABLE VIII CY8to8copic Finding8 in 106 Ca8e8 General collar enlargement of the prostate gland with or without irregularities ............................ Trabeculation of bladder mucosa ..................... Median lobe enlargement ........................... One or both lateral lobes enlarged .................... Tumor in bladder .................................. Diverticulum in bladder ............................ Stone in bladder ................................... Been in Docurred 50 cases 46 cases 36 cases 22 cases 17 cases 13 cases 8 cases once in 2.1 times once in 2.3 times once in 2.9 times once in 4.8 times once in 6.2 times onee in 8.1 times once in 13.0 times showed some degree of trabeculation or corrugation of the bladder mucosa. This finding is not of special interest, however, in carcinoma of the prostate, as it is commonly seen in cases of urinary obstruction. Dossot (20) mentions the fact that in carcinoma of the prostate the bladder is frequently increased in volume and its internal surface is trabeculated, with more or less distinct cellules, an appearance which he believes is definite, especially in adenoid cancer. Other findings on cystoscopic examination are those of prostatic hypertrophy, which are not of special interest in this connection. METASTASES Geraghty (21) states that in 21 of 400 cases of carcinoma of the prostate the process was confined to the gland. Barney and Gilbert (7) estimate the percentage of cases with metastases in their series as 58 per cent. In Bumpus' series (22) 28 per cent of the patients had bony metastases when they were first seen. Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1035 In 98 per cent of Barringer's cases (23) the carcinomatous growth had already grown beyond the prostate when the patient first was seen. Of 197 cases in this series, 101, or 51.3 per cent, presented demonstrable lesions beyond the prostatic gland, and in 80 cases or 40.6 per cent the process had extended beyond the prostate and the seminal vesicles. TABLE IX Extension and Distribution of Metastases in 197 Cases (103 cases, 52.2%. with extension beyond the prostate; 80 cases, 40.6%, with extension beyond the prostate and seminal vesicles; 36 cases with metastatic bone lesions) DIRECT ExT1llNSION Seminal vesicles. . . . . . . . . . . . . .. .. 39 cases Bladder " 21 cases Rectum. .. .. .. .. . .. .. .. . .. .. .. . 4 cases Urethra and perineum. . . . . .. .. .. 1 case Ureter and kidney. . . . . . . . . . . . . . . 1 case MIIlTASTATIC LESIONS Lymphatic Sylltem lnguinallymph nodes. . . . . . . . .. Retroperitoneal nodes Mediastinal lymph nodes. . . . . . . Substernal lymph nodes. . . . . . . . . Supraclavicular lymph nodes. . . . Cervical lymph nodes. . . . . . . . . . . Axillary lymph nodes. . . . . . . . . . . Lungs .. " " .. .. .. .. Liver. . . . . . . . . . . . . . . . . . . . . . . . . . Peritoneum. . . . . . . . . . . . . . . . . . . .. Large intestine.. . • . . . . . . .. .. .... Kidney. . . . . . . . . . . . . . . . . . . . . . . . . Pleura. .. .. .. .. . .. . .. .. • .. .. .. . Myocardium. . . . . . . . . . . . . . . . . . . . Abdominal wall (cystostomy wound) Brain. . . . . . . . . . . . . . . . . . . . . . . . . . Bones Pelvis Vertebrae Femur. . . . . . . . . . . . . . . . . . . . . . . Ribs. .. .. .. .. .. .. .. .. .. .. .... Shoulder girdle. . . . . . . . . . . . . . .. Skull. . . . . . . . . . . . . . . . . . . . . . . .. Humerus, . . . . . . . . . . . . . . . . . . . . Mandible " .. .. .. .. Patella. . . . . . . . . . . . . . . . . . . . . . . 13 cases 10 cases 4 cases 1 case 1 C88t' 1 case 1 case 8 cases 7 cases 4 cases 3 cases 2 cases 2 cases 1 case 1 case 1 case 22 cases (1 in 1.6 caseswith skeletal metastasis) 19 cases (l in 1.9 cases with skeletal metastasis) 6 cases (1 in 6.0 cases with skeletal metastasis) 8 cases (1 in 6.0 caBe8 with skeletal metastasis) 4 cases (1 in 9.0 cases with skeletal metastasis) 3 cases 2 cases 1 case 1 case The distribution of the metastases in this series is given in Table IX. Only 15 cases were autopsied and of these only 5 were found with metastases (Table X). The skeletal metastatic lesions and the secondary growths in the lung were revealed by the x-ray. While the extension of the carcinomatous process to seminal vesi- Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1036 JOHN R. CAULK AND S. B. BOON-ITT eles and to rectum W8B diagnosed by digital palpation, the diagnosis of other metastatic localization W8B reached after the usual physical examination. In some C8Bes the abdominal metastatie lesions were visualized through operative wounds. TABLE X Necropsy Findings in 17 Cases (15 Primary; e Metastatic) PRlMARY CARCINOMA OF PROSTATE No sign of metastasis in Metastasis in. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Retroperitoneal nodes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mediastinal nodes " Bladder. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Peritoneum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pleura " Perineum and urethra. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Axillary lymph nodes " " Ureter and kidney. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kidney. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 cases 5 cases 3 cases 3 cases 2 cases 2 cases 2 cases 1 case 1 case 1 case 1 case In~llymphnodes 1 case Myocardium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 case Liver. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 case Pelvis, ribs, and vertebrae : " 1 case METASTATIC CARCINOMA OF THE PROSTATE Primary carcinoma of the stomach with general metastasis including the prostatic gland. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 case Primary carcinoma of bladder with extension to the prostate and metastasis to adrenal and myocardium. . .. .. .. . . . . . . .. . . . . . .. . . . . . .. .. . . .... 1 case Extension of the carcinomatous process via seminal vesicles appears to predominate, with spread to the pelvic bones ranking next. Barringer (14) and Young believe that the commonest extension of carcinoma of the prostate is toward the seminal vesicles, the next most favored line of extension being laterally from the prostato-vesicular junctions to the rami of the pubic bone. The findings in this series are entirely in accordance with this view. One would expect to find the extension of the growth to the seminal vesicles more frequent than once in about 5 cases, as in this series. It is to be recalled, however, that early carcinomatous lesions of the vesicles are very easily missed by the palpating finger. Dossot (20) also is of the opinion that carcinoma of the prostate frequently extends toward the seminal vesicles, and further believes that invasion of the bladder is quite frequent. Among his 89.4 per cent of cases with adenopathy, he observed only 3 cases with involvement of the inguinal lymph nodes. In Bumpus' series (13),46.1 per cent of the cases had glandular metastases, with the inguinal lymph nodes heading the list. In this series, also, the Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1037 inguinal nodes head the list of glandular involvement. This is readily explained by the fact that these nodes are superficially situated and are therefore easily accessible to the palpating finger, while early involvement of the iliac and retroperitoneal glands is in most cases not palpable. Of Bumpus' cases (13), 51 per cent had secondary growths in the bones, with the pelvic bones as the most frequent site. Young (6) states that prostatic carcinoma commonly metastasizes to the pelvis and vertebrae. Ewing (10) ranks carcinoma of the prostate as first in metastasis to the osseous system. Kaufmann calculated that about 70 per cent of prostatic carcinomata cause skeletal metastases, as compared with 37 per cent for thyroid carcinomata (Limacher) and 14 per cent for mammary carcinomata. In the present series only 19 per cent of the cases are known to have skeletal lesions. This relatively small number is due to the fact that only a few patients, and generally only those in whom bone metastasis was strongly suspected, were sent for x-ray pictures. For this reason the percentage in relation to the total number of cases is too low, while that in relation to the number of cases x-rayed is too high to be fairly representative. It will be observed in Table IX that the pelvic bones were the site of metastases once in every 1.6 cases, and the vertebrae once in every 1.9 cases of carcinoma of the prostate with skeletal metastasis. The tendency of carcinoma of the prostate to distant dissemination is well recognized. Charteris (24) reports a case with metastasis to the skull and other bones, in which post-mortem examination revealed only slight enlargement of the glands along the iliac vessels, while the abdominal viscera had completely escaped invasion. Charteris could not reconcile these findings with metastasis by way of the lymphatic stream. In his opinion, the facts are more in accordance with blood stream dissemination. Piney (16) is also of the belief that metastasis to the bones from a primary growth in the prostate is by way of the blood stream. He further demonstrates that there is no evidence of lymphatic channels in the bones. Roberts (17), however, maintains that it is not certain that the blood stream plays any important role in the spread of cancer cells from the prostate. He explains metastasis to the lower extremities by way of the lymphatic plexus surrounding the blood vessels to the bones. He further suggests a route of spread through the lymphatic vessels and tissue spaces of the spinal laminae, with their associated ligaments, by which malignant cells Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1038 JOHN R. CAULK AND S. B. BOON-ITT may reach the vertebrae, ribs, skull, and other bones. This will explain the non-involvement of the lymphatic system in the abdomen in cases with metastasis to the skull and bones of the upper extremities. Roberts reports three cases with lesions in the spinal laminae with their ligaments to corroborate his suggestion. At present the weight of,evidence, such as the finding of iliac lymphatic enlargement in autopsied cases, seems to suggest that the malignant cells commonly pass from the primary site via the lymphatic system. This fact is of value in early treatment. One of the cases in this series had metastasis to the myocardium, which is a comparatively rare site for secondary growth. In another case brain metastasis was present, with symptoms of paralysis of the glossopharyngeal and hypoglossal nerves. This patient also had metastatic lesions in the spine. 'Extensions of carcinoma from the prostate to surrounding parts-urethra, bladder, and rectum-occur as late manifestations and are far less frequent than metastatic changes. Only a few of our cases showed urethral extension. Bladder invasion, except for the usual obstructive condition at the orifice, occurs usually from implication through the seminal vesicles. The rectum is protected by Denonvillier's fascia and is involved as a part of an invasive process. Like the bladder, it derives its lesions more commonly from the seminal vesicles. It is usually for the relief of pain in the back, along the sciatic nerve, or during the act of urination, that such patients consult a physician. By that time the disease has extended, in many cases, too far for repair. Many observers are deceived into thinking that an apparently cachectic patient is beyond relief, when, as a matter of fact, the condition is due to uremia and toxemia, the result of obstruction. In such cases, if the obstruction be removed by proper treatment, tremendous help may be afforded and the patient, although still suffering from cancer, may enjoy additional years of comfortable living. No such case, therefore, should be considered as hopeless. In every instance the obstruction should be relieved. An opportunity is thus given to determine the comparative effects of the uremia and toxemia due to the obstruction and the devastation due to the cancer. TREATMENT The results of different methods of treatment reported in the literature vary considerably. No attempt is made to review them all. In some hands the radical prostatectomy of Young proves Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1039 successful. Among the 26 cases reported by Smith (27) in which total prostatectomy was done, there were 3 deaths in the hospital; 8 patients died after leaving the hospital, having lived an average of twenty-two months after operation, and 15 were still living at varying periods up to six years after operation. Barney and Gilbert (7) conclude from their study that surgery alone is better than radium alone, but the combination of the two is often advantageous. Chute (25) advises simple prostatectomy in all instances where the malignant process produces obstruction to urination, but believes that radium should be used in conjunction with surgery. Bumpus (22) reports that the results of radium treatment of cancer of the prostate in his series are inferior to those obtained by surgery, but he, also, is of the belief that a combination of surgery and radium offers the best results. Barringer (14), on the other hand, states that his results show the superiority of radium treatment over operative treatment both in causing regression of the growth and in coping with the urinary symptoms. Geraghty (21) stated that in 95 per cent of cases of carcinoma of the prostate surgery alone is hopeless. He was of the opinion that radium had a definite field of usefulness. Smith and Peirson (26) advocate x-ray treatment for cases not suited for surgical removal. The treatment of the cases in this series varied at different times and with different surgeons. Some cases were treated by simple prostatectomy, either by the perineal route or through a suprapubic incision, in one or two stages, while others received radium or x-ray, or both, in addition to surgery. The radical prostatectomy of Young was not employed in any of the cases. More recently a more conservative treatment has been adopted. The cautery punch has been used to relieve obstruction, and radium, either in combination with x-ray or alone, has been given to retard the growth. The punch operation was performed in one or more sittings according to the requirements of the individual case. Radium was formerly given by inserting needles, containing 12.5 mg. of radium, into the prostate and leaving them in the glandular tissue for a certain length of time according to the amount of the treatment required. More recently radon seeds, from one to two millicuries each, have been used. From 6 to 10 seeds are implanted into the prostate and vesicles with the aid of two small trocar needles inserted through the perineum into the prostate gland. Deep x-ray therapy is usually given a few weeks later, Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1040 JOHN R. CAULK AND S. B. BOON-ITT although at times it precedes the radium implantation. The x-ray treatment is generally administered in divided dosage, regulated by the x-ray department. It is the general practice to repeat both x-ray and radium treatments at intervals of two to four months. In some cases where surgery is believed to be contraindicated, only radium and x-ray are given. It is the policy of the Service to supplement surgical treatment of all cases of carcinoma of the prostate by radium or x-ray therapy or by combined radium and x-ray treatment, but this is not always possible. The experience at Barnes' Hospital with radium therapy coincides very closely with that of other clinics. The enlarged and stony-hard cancerous prostate is readily reduced in size and becomes softer after radium or radon implantation. It is observed, however, that radium causes more tissue reaction than radon. In one of the cases treated with radium needle implantation a prompt reaction resulted in a dense fibrosis of the orifice, which required sharp dissection. Histologically the tissue was entirely scar tissue. A recontracture promptly occurred, which necessitated permanent suprapubic drainage. In using radon seeds, we have never observed any such unfortunate complication. A number of patients came to the clinic with practically hopeless metastases. They had marked urinary disturbances, with much discomfort and pain on urination. In such cases the punch operation has proved useful. The removal of a few bites with the cautery punch generally renders urination free and practically painless. This permits the patient to enjoy the few remaining months of his life in comfort. Deep x-ray therapy is found to be very useful in shrinking and softening the carcinomatous gland, as well as in the treatment of back pain and the sciatica-like pain of the lower extremities. In our experience, however, it has no therapeutic influence on the deep-seated pain of the hip joint. In only 143 of this series of 218 cases of primary carcinoma of the prostate are the follow-up records suitable for a study of the results of treatment. These cases are grouped according to the type of treatment received. The duration of life after treatment by the various methods has been averaged. Of these 143 patients, variously treated, 36 (25.1 per cent) lived three years or more after treatment, and 25 of these (17.4 per cent of the 143 cases) four years or more after treatment. The analysis of the results of treatment in this series of cases has been supplemented by graphic representations showing the Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1041 CARCINOMA OF THE PROSTATE duration of life after the different types of therapy. Those patients dying while in the hospital, as the result of operation or complications thereof, and those in whom the disease had developed beyond therapeutic aid and who were brought to the hospital to pass their few remaining days in as much comfort as possible, are not included in the graphic series, since their inclusion P1'Ol!lt4tectomy "tone i __ o Punch alone 13 10 g I 1 1 :: Years X-!'ay alone 13 i u ;.', 6 9 10 Radium alone No t!'eatment 16 1~ 10 10 11 0- 10 ~ 1 4 6 GRAPH 1. DURATION OF LIFE AFTER DIFFERENT TyPES OF THERAPY would not give a true representation of the benefits derived from therapy. The graphs are intended to show the relative value of the different types and combinations of therapy in prolonging life. The first column to the right of the scale indicates the total number of cases treated by the particular type of therapy, the black portion of that column indicates the total number of deaths. The drop in the black portion of the column from year to year, therefore, indicates the number of deaths during the preceding Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1042 JOHN R. CAULK AND 8. B. BOON-ITT year. The drop in the total column is accounted for by deaths, by patients whose treatment has been too recent to include them, and by those in whom a follow-up could not be obtained. Graphs 1, 2 and 3 show the results from different types of treatment. Graphs 4 and 5 are composites, showing the results from treatment other than surgery, and from all prostatectomy Punch and en ~u ~dium. Prostatectomy and l'adium 10 10 0- ~ 5 1,. 1, 1 1 '" ".: Yeat>5 1 2 3 4 S 6 7 6 9 10 11 20 s~u 1)- 18 20 'Punch and x-ray 16' US 10 10 'P['ostatectomy and x-ray 6 ~ ~ GRAPH S 2. DURATION OJ' LIFII Arrma DIJ'J'IlRIINT fins OJ' THIlRAPY and cautery punch cases alone and in combination with radium or x-ray. A discussion of the graphs will be limited to 4 and 5, the nonsurgical and surgical groups and the cautery punch cases, with occasional reference to the preceding graphs. Those cases treated non-surgically, that is, with radium or x-ray, or both, show a sudden drop in the curve the first two years, leaving only 3 patients, or 12.5 per cent, living over three years and only one patient living more than five years. Those patients having prostatectomy alone were Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1043 CARCINOMA OF THE PROSTATE naturally patients who were good surgical risks; 50 per cent of those who lived after the operation were clinically benign cases, carcinoma having been detected in an otherwise benign hypertrophy by histologic examination. In such cases the duration of life would naturally be expected to be longer than in frank cancer cases. The operative mortality in prostatectomy done for cancer was 17 31 Punch.redium and x-roay 16 10 Radium and x-!'ay 9 5 I 1 20 Years 15 1 1 4 .5 6 Proetatectomy; rediurn and x-f'i!ij 10 10 3 1 Yeers GRAPH 3. DUBATION 01' LIn 1 2 3 4 6 ArrER DIl"JI'ERJIlNT TyplllS 01' TmlRAPY per cent. In the cases treated by prostatectomy alone, the average duration of life was forty-four months, while patients having prostatectomy supplemented by either radium or x-ray therapy or by both in combination had an average duration of life of only twenty-five months. Not one patient of this latter group lived five years. It is to be observed in Graph 4 for prostatectomy cases that there is a more gradual decline in the curve. This is due to the simple prostatectomy cases including clinically benign lesions. The drop in the curve is more gradual, but in itself is pronounced. All of these patients died within five years. It seems definitely as Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1044 JOHN R. CAULK AND B. B. BOON-ITT unsurgieal to attempt to II gouge out" a carcinoma of the prostate suprapubically as it does to attempt the same type of enucleative procedure for a cancer of the breast. Since the completion of the tabulations for this paper about a year ago, I have analyzed all the punch cases from many different angles and standpoints, and will present them to date. It will be observed on Graph No. 5 that there is a sudden drop in the curve for the first two years, which results from the fact that the majority of these patients were very poor risks, many entirely 30 Tr>eatmente othel' than 2" 30 ,AU ~urgef')' Il4 ~l!Itatectomy cases 23 ~ 20 .: ': :\ " " 20 ~ 0~ " " 1~ ItJ " ~~: '. " ;. " 10 10 .~ ~~ -', ::. "'.; :;,: ~'f\ :. ., \::: ~ .... ::. " ~I\ .;: I ,; 'I i~ 1 2 3 4 GRAPH 4. DURATION OJ' s 6 LInl ArrmB NON-SUBOICAL TREATMENT AND PaOBTATIlCTOKY inoperable. From this time on, unlike the prostatectomy graph, the curve is more gradual. At the end of three years 29 per cent of the patients are living and at the end of five years 10.7 per cent still survive i one patient is living after ten years. A critical analysis of the punch cases follows: There were 80 white patients and one colored one. This disproportion is due to the fact that the majority of these patients were seen in private practice. In this group there were 40 early cases and 41 advanced cases. I have designated as early those cases in which there were localized nodular areas in the prostate without evidences of extension beyond its confines, with seminal vesicles, membranous urethra, and rectum apparently normal, and Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 70 M AU punch caee& 6~ : " " 50 " ~~ " ',' " " ~O .•." ~ 4 4.5 40 U'l C\) U '5"" ~ S: :.: :-.: :... :. ~ ," " " " " ~: ',' " .;. U'l co :.: 3.5 1\ :0° " " :::' 30 ~: "" 2~ 20 1.5 10 GBAPH 5, DURATION OF 1IFJIl ArrBla PuNCH OPERATION 1045 Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1046 JOHN R. CAULK AND S. B. BOON-ITT without demonstrable evidence of metastases. This, of course, is quite indefinite, since it is impossible to determine whether or not the deep pelvic glands are involved. In a number of instances in which the prostates showed apparently early lesions, the diagnosis of cancer being difficult, there was pronounced dissemination. Of the 81 patients, I have been able to follow 69, or 85 per cent. Of these, 27 are living and 42 have died. Thirty of these died of cancer, 12 of other causes, including pneumonia, heart conditions, apoplexy, pyelonephritis, and following a later operation done elsewhere. Two deaths resulted from the punch operation; in both instances the individuals were extremely depleted. The time of death was as follows: within six months to a year, 8 cases; within two years, 11 cases; three years, 3 cases; four years, 1 case; five years, 3 cases; six years, 3 cases; over six years, 1 case. In the total series of cases, the punch operation was done in 83 per cent combined with x-ray or radium or both. Of these patients, 67 per cent had single operations and 33 per cent multiple; 13.5 per cent of the multiple operations were for recurrence of the disease. Seventy-four per cent of the patients were treated with x-ray, 52 per cent with radium; 17 per cent of the total number were treated by the punch alone. The majority were cases with extensive metastases, in which relief of obstruction alone was the aim. A few refused x-ray and radium. The results of the combinations of treatment are as follows: FIRST GROUP Radium, x-ray and punch: 35 cases (43 per cent) Those who died lived an average of twenty-seven months. Those who are living average twenty-five months since the beginning of treatment. Many of them are in good condition. SECOND GROUP X-ray and punch: 25 cases (30 per cent) Those who died lived an average of seventeen months. Those who are living average thirty-eight months since the beginning of treatment. THIRD GROUP Radium and punch: 7 cases (9 per cent) Those who died lived an average of thirty months. Those who are living average ninety months since the beginning Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1047 of treatment. This latter figure is striking, but concerns only two patients, both with low-grade malignancy, who have remained well one five and one ten years. In both instances the specimen removed with the punch showed cancer. FOURTH GROUP Punch alone: 14 cases (17 per cent) Those who died lived an average of twenty-four months. Those who are living average thirty months since the beginning of treatment. Of the 40 early cases, 14 lived three years or more (35 per cent). Of the 41 advanced cases, 6 lived three years or more (14.6 per cent). Of the 14 early cases with a survival of over three years,S had small prostates, 7 had moderate enlargements, 2 extreme growths. Of the advanced cases, 1 had a small growth and 5 larger growths. There were, therefore, but 6 patients with small prostates among the 20 who lived over three years, as compared with 14 with larger ones. This demonstrates a decided tendency of the larger growths to be less malignant, or at least more responsive to therapy. To analyze further this group of 20 patients surviving over three years, there were 14 early cases, treated by: x-ray and punch, 2 cases; radium and punch, 4 cases; x-ray, radium, and punch, 5 cases; punch alone, 3 cases. Of the 3 cases treated by punch alone, the punch specimen was positive for cancer in one, one died four years later of cancer, and one is living with definite evidence of general carcinoma. Sixlate cases were treated by: x-ray and punch, 3 cases; x-ray, radium and punch, 3 cases. In other words, 29.0 per cent of all the patients lived over three years. Deducting the 13 cases in which the punch alone was used because the condition was inoperable and the sole aim was to relieve urinary obstruction, with no attempt to abate the disease, there were 16 patients, or 30 per cent, living over three years. Of the 20 cases, the specimens removed from the orificeby means of the punch showed definite cancer in IS, or 83.3 per cent, benign hyperplasia in 3, or 16.6 per cent; in 2 cases there was no examination of the specimen. This definitely indicates the presence of cancer at the internal orifice of the prostate. In many instances the disease appeared to be localized and early. Ten of the 12 early cases gave a positive picture of cancer. Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1048 JOHN R. CAULK AND B. B. BOON-ITT Ten per cent of the total series have lived or are living over five years. Of these, 6 were early cases, 2 advanced; 5 showed enlargement, in 3 the prostate was small. Of the 2 advanced cases, the prostate was small in one and large in one; both were controlled by repeated massive doses of x-ray therapy. In 7 of the 8 patients, the tissue removed by the punch showed carcinoma. The treatment employed in these patients was x-ray and punch in 2 instances; radium and punch in 2; x-ray, radium, and punch in 2; punch alone in 2. Specimens were removed from 64 patients; in 52, or 81 per cent, positive evidence of cancer was obtained, while 19per cent were benign. In other words, the removal of specimens from the internal orifice of the bladder in obstructions suggestive of carcinoma will aid in disclosing the true diagnosis of the disease in 81 per cent of the cases, thereby stamping it as a valuable aid in such diagnosis. Altogether there are 26 patients living who have had the cautery punch operation. The results are designated below, the follow-up ranging from six months to ten and a half years. Six months Six months to a year .. " One to two years. . . . . .. Two to three years Three to four years ..... Four to five years. . . . . .. Five to six years Nine years " Ten and a half years .... 1 case. Complete relief of obstruction; patient in good condition 4 cases. All with relief of obstruction 8 cases. Relief of obstruction in 5. Of the other 3, one did not return, as he was advised; one has a recurrence and is about to undergo another operation; the other received no benefit 3 cases. Complete relief of obstruction in 2; 1 poor result (prostatectomy within the last six months by another surgeon) 3 cases. Complete relief of obstruction in 2; 1 on catheter life (tremendous prostate) 3 cases. All with complete relief 2 cases. Both with complete relief 1 case. Symptomatically perfect; carries 2 ounces of residual urine. Good general condition 1 case. No residual urine. Good general condition Of the -total number of cases, 77 per cent received complete relief of obstruction; 23 per cent were either partially benefited or received no relief. Forty-two patients have died. Of these, there are records of the condition of the bladder at the time of death in 40 cases. Thirty (71 per cent) died from cancer. Of these, there are definite records as to the bladder condition in 28. Twenty (71 per cent) had complete relief of obstruction. Six had partial relief. Of these 6, 3 were in such poor condition as to preclude further surgery of even this minor type. The other 3 refused further surgery. Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1049 Twelve (29 per cent) died from other causes than cancer. Two died from hemorrhage following operation. Both these patients were extremely poor risks with general metastases, and one was a hemophiliac. Five of the remaining 10 had complete relief of obstruction; 5 had but partial relief. Of the q4 cases which have been studied, 46, or 72 per cent, obtained complete relief of obstruction. METASTATIC CARCINOMA OF THE PROSTATE This paper has been concerned chiefly with primary cancer of the prostate. A note may be added on metastatic cancer of the prostate. There are four cases in this series of 222 cases in which the primary site was elsewhere than in the prostate, 3 of these definite and the fourth questionably so. Three patients entered the hospital with the chief complaint referable to the gastro-intestinal tract and with no symptoms suggestive of a genito-urinary lesion. Physical examlnation resulted in a diagnosis of carcinoma of the stomach with carcinoma of the prostate. All three patients died in the hospital, but autopsy was obtained in only one case. In this case necropsy showed carcinoma of the stomach as the primary lesion, while the growth in the prostate was proved to be metastatic. In the other two cases the growths were visualized through the laparotomy wound. They were definitely carcinoma of the stomach with extensive metastases to the abdominal viscera. There was probably metastasis to the prostate, also. While it is possible that in these last two cases the carcinoma of the prostate may have been an independent growth, co-existing with a similar growth in the stomach, this would seem less probable than that the lesion was metastatic. These reports issue from a general pathological laboratory where there is unquestionably entire familiarity with the usual tendency of carcinoma of the prostate to be primary and to metastasize to the abdominal cavity. In the fourth case, the prostatic lesion of which was not definitely established as being primary, the clinical diagnosis was carcinoma of the prostate with extension to badder, chronic cystitis, stricture of the urethra (metastatic), and myocarditis. The autopsy findings were as follows: The bladder is large and contains a large amount of reddish, purulent, foul-smelling material. The prostate is separated from the symphysis with difficulty and when removed presents a ragged necrotic mass. This Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1050 JOHN R. CAULK AND S. B. BOON-ITT whole area, as well as a large portion of the bladder about the neck, is infiltrated with a firm white mass of tissue. A probe passes through the posterior urethra and into the bladder with some difficulty. It cannot be determined whether there is any destruction distal to the posterior urethra. The bladder mucosa. is dirty and covered with a necrotic, purulent, gray exudate. The rectum is separated with difficulty from the posterior part of the bladder. Microscopic section near the dome of the bladder shows islands of tumor cells still in the mucosa and submucosa. In the section about the trigone the tumor cells have already extensively infiltrated the muscularis layer. In places the islands of tumor cells have a somewhat papillomatous arrangement, with a basement membrane of connective tissue. The heart weighs 310 gm. The myocardium of the left ventricle averages 20 mm. in thickness and is infiltrated with a number of nodules of firm white tissue with a faint yellow tint. Some of these encroach upon the myocardium of the left ventricle, so that they project as elevated irregular masses into the ventricular cavity. The valves are all normal. The coronary vessels appear to be normal. Microscopic section shows muscle infiltrated with frequent islands of tumor cells. These cells are large and contain large dark nuclei. Mitotic figures are frequently observed. The arrangement is that of the squamous epithelium of the bladder mucosa. The suprarenals are rather small but normal in appearance. The microscopic section contains a small area of tumor islands, the cells lying on a basement membrane, as those seen in section of the heart. The nuclei are hyperchromatic, and the intercellular bridges cannot be made out, although the cells have the appearance of squamous-cell epithelium. Anatomical Diagnosis: Primary carcinoma of bladder, with extension to the prostate; metastases to myocardium and suprarenal. Ewing (10) classifies carcinoma of the prostate into two groups, 1/ adenocarcinoma" and " carcinoma." The latter group he further divides into 1/ scirrhous carcinoma" and "squamous epithelioma." The microscopic sections of the above case give the picture of squamous epithelial tumor with a cellular arrangement similar to that of the bladder mucosa. It may be that this is a carcinoma of the prostate gland of the squamous epithelioma type as classified by Ewing. It has been shown by Aschoff and Sehlachta (quoted by Ewing) that in the upper portion of the fetal prostate, the ducts are lined by squamous epithelium up to the third month of life or later. Schmidt observed extensive epithelial metaplasia in chronic suppurative prostatitis. Would it not be possible, therefore, that the remnant of this squamous epithelial tissue of the prostate might become the primary seat of the new growth and that this might later extend directly to the bladder neck? The metastatic lesions would thus naturally be of squamous-cell type. Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. CARCINOMA OF THE PROSTATE 1051 SUMMARY The frequency of prostatic cancer warrants attention and demands early recognition. Chronic inflammation of the prostate may be a predisposing cause. The cautery punch operation in conjunction with radium and x-ray therapy appears to be the method of choice for relieving obstruction and retarding the progress of the disease. Seventy-two per cent of the cases thus treated received complete relief of obstruction. Twenty-nine per cent of the patients lived or are living over three years, 10 per cent over five years, a longer duration of life than that afforded by prostatectomy. The mortality from the operation, in spite of the fact that it was done in many instances upon extremely ill patients, upon whom prostatectomy would not have been considered, is 2.5 per cent. The mortality rate from prostatectomy in this disease in our clinic is 17 per cent. Hospitalization has been less than with prostatectomy. The punch operation affords a definite means of accurately diagnosing cancer of the prostate in 80 per cent of all cases, early or late, which indicates that the disease, even in apparently early cases, is present throughout the substance of the gland. REFERENCES 1. OERTEL, H.: Involutionary changes in prostate and female breast in relation to cancer development, Canad. M. A. J. 16: 237, 1926. 2. CHEATLE, G. L., AND WALE, R. S.: A lesion common to breast and prostate glands, Brit. J. Surg. 17: 619, 1930. 3. MARK, E. G., AND MCCARTHY, H. E.: Carcinoma of prostate, J. Missouri State M. A. 14: 71, 1917. 4. HOFFMAN: The mortality from cancer throughout the world, Prudential Press, Newark, N. J., 1915. 5. BUREAU OF CENSUS: Mortality Statistics, 1927, Twenty-eighth Annual Report, U. S. Government Printing Office, Washington, D. C. 6. YOUNG, H. H. : Tumors of prostate, Practice of Surgery, ed. by Dean Lewis, W. F. Prior Co., Hagerstown, Md., Vol. IX, chapter 21. 7. BARNEY, J. D., AND GILBERT, A. C.: Some clinical observations on carcinoma of prostate, Boston M. & S. J. 190: 19, 1924. 8. CUNNINGHAM, J. H.: The treatment of carcinoma of prostate, Boston M. & S. J. 186: 99, 1922. 9. HERMANN, H. B.: Metastatic tumors of the urinary bladder originating from carcinoma of the gastro-intestinal tract, J. Urol. 22: 257, 1929. Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research. 1052 JOHN R. CAULK AND S. B. BOON-ITT 10. EWING, J.: Neoplastic Diseases, W. B. Saunders Co., Philadelphia, 1928, 3d ed., pp. 825-831. 11. BUGBEE, H. G.: Cases of unsuspected carcinoma of the prostate discovered on microscopic section, J. Urol. 22: 263, 1929. 12. HIRSCH, E. F., AND SCHMIDT, L. E.: Small carcinomas of prostate, J. Urol. 20: 387, 1928. 13. BUMPUS, H. C., JR.: Carcinoma of prostate, Surg. Gynec. & Obst. 32: 31, 1921. 14. BARRINGER, B. S.: Carcinoma of prostate, Trans. Am. Assoc. GenitoUrin. Surg., May 1921, p. 95. 15. 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CHUTE, A. L.: Some aspects of cancer of the prostate, Trans. Am. Assoc. Genito-Urin. Surg., May 1921, p. 85; Boston M. & S. J. 185: 500, 1921. 26. SMITH, G. G., AND PEIRSON, E. L.: The value of high voltage x-ray therapy in carcinoma of prostate, J. Urol. 23: 331, 1930. 27. SCHREINER, BERNARD F.: The results of treatment of cancer of the breast, Ann. Surg. 93: 269, 1931. 28. HUNT, V. C.: Carcinoma of prostate gland and prostatic capsule developing subsequent to prostatectomy for benign prostatic hypertrophy, J. Urol. 22: 351, 1929. 29. SMITH, G. G.: Total perineal prostatectomy for cancer, J. Urol. 22: 377,1929. 30. SMITH, G. G.: Carcinoma of prostate, New England J. Med. 202: 756,1930. Downloaded from cancerres.aacrjournals.org on June 15, 2014. © 1932 American Association for Cancer Research.
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