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Carcinoma of the Bladder in Patients Less than 40 Years Old
0022-5347/78/1202-0172$02.00/0 THE JOURNAL OF UROLOGY Copyright © 1978 by The Williams & Wilkins Co.
Vol. 120, August
Printed in U.SA.
CARCINOMA OF THE BLADDER IN PATIENTS LESS THAN 40 YEARS OLD D. E. JOHNSON
AND
S. HILLIS
From the Section of Urology, Department of Surgery, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas
ABSTRACT
The records were reviewed of 22 patients with bladder carcinoma before they were 40 years old to determine whether age alone influenced the course of the disease. There were 19 men and 3 women, reflecting a male predominance of 6 to 1. Of the 9 patients with superficial stage A/0 disease 8 are alive 6 months to 28 years after diagnosis, the remaining patient being lost to followup. The other 13 patients with tumors invading muscle are dead, 11 as a direct result of the disease. No evidence was found to substantiate earlier reports that bladder carcinoma in young patients has a more benign behavior. The incidence of bladder carcinoma increases with patient age, with the peak incidence being in the sixth decade oflife. 1 Although neoplasms are rare in patients less than 40 years old the available information suggests that the clinical course of vesical carcinoma is more benign in younger patients. Javadpour and Mostofi reviewed 40 cases of primary epithelial tumors of the bladder in patients less than 21 years old and found that the tumors were mostly transitional, papillary and non-infiltrating. 2 They also found that these tumors were of low grade malignancy, with a favorable prognosis. Likewise, McGuire and associates recently reported the benignity of the disease in their review of 62 patients with transitional cell carcinoma before the age of 21 years. 3 However, McCarthy refuted the belief that these tumors fail to recur by reporting a recurrence rate of 14 per cent in 79 cases of transitional cell carcinoma in patients less than 30 years old. 4 The recurrences frequently were more aggressive and more malignant. To better define the relationship between the biological potential of bladder carcinoma and the age of the patient we reviewed our experience with 22 patients less than 40 years old with proved vesical carcinoma. MATERIALS AND METHODS
The records were reviewed of 2,139 patients with malignant neoplasms of the bladder who were treated from March 1944 to September 1975. In 22 patients (1 per cent) epithelial carcinoma was diagnosed before they were 40 years old. In each case the diagnosis was confirmed by histologic review of the excised tissue. The lesions were classified and graded according to the recommendations of the World Health Organization. 5 Clinical staging of the disease, using endoscopy and palpable findings, was done in 21 cases according to Marshall's modification of the Jewett and Strong classification. 6 RESULTS
Clinical findings. There were 19 men and 3 women, reflecting a male predominance of about 6 to 1 (see table). Patient age at diagnosis ranged from 25 to 39 years, with an average of 35. 7 years. The most common symptom was gross hematuria (15 patients) with an irritable bladder as part of the symptom complex in 7 of the 15 patients. In 1 patient only symptoms of vesical irritability were present. In 1 instance each the lesion was found incidental to an evaluation for 1) microhematuria discovered at routine physical examination, Accepted for publication October 7, 1977. Read at annual meeting of Southeastern Section, American Urological Association, New Orleans, Louisiana, March 27-31, 1977. 172
2) urinary calculi and 3) metastatic subcutaneous mass. Presenting symptoms were not recorded in 3 cases. The mean duration from onset of symptoms to diagnosis was 6 months in the 17 cases in which this information had been recorded. Cystoscopic evaluation revealed exophytic (papillary) lesions in 10 patients, and endophytic (sessile) and solid-appearing lesions in 6 patients; the initial growth description of the tumor was not available in 6 patients. At diagnosis the lesions were staged O in 4 patients, A in 5, Bl in 3, C in 5, Dl in 2 and D2 in 1. In 2 patients the disease could not be assessed adequately at initial evaluation. The lesions were classified histologically as transitional cell carcinoma in 17 patients, squamous carcinoma in 3 and adenocarcinoma in 2. Treatment. Transurethral resections were done in 11 of the 12 cases of superficial disease (stages 0, A and Bl). Subsequently, recurrences were demonstrated in 4 of these patients. One patient with stage Bl disease underwent radical cystectomy with ileal conduit diversion. Treatment for patients with locally invasive disease (stage C) consisted of preoperative radiotherapy followed by cystectomy and ileal conduit diversion in 3 cases, partial cystectomy in 1 and radical cystectomy in 1. All 3 patients who had either regional metastases (stage Dl, 2 cases) or disseminated disease (stage D2, 1 case) received palliative radiotherapy directed to the primary tumor. Survival. Of the 9 patients with superficial stage 0/A disease 8 are known to be alive 6 months to 28 years after diagnosis, the remaining patient being lost to followup. The other 13 patients are dead, 11 as a direct result of the disease. The median survival time for this group was 11 months. DISCUSSION
The clinical features of vesical carcinoma differ little between patients less than 40 years old and those older. The only apparent differences are that patients less than 40 have less propensity for multifocal disease and reduced potential for recurrences, and the disease in this group occurs predominantly in men. 3 While previous investigators have suggested that epithelial neoplasms of the bladder in young patients are clinically and morphologically benign3 • 7- 9 infiltrating tumors have been reported, 5 the youngest patient being a 3-year-old girl. 3 Consequently, a diagnosis of bladder carcinoma should be considered in all patients with hematuria, regardless of age, and a thorough urological evaluation should be done. In reviewing 9 cases of vesical carcinoma in the young, Benton and Henderson found evidence in 6 to incriminate chemical carcinogens as an etiological factor. 10 Although our records preclude a definite statement regarding etiological factors chemical carcinogenesis should be suspected in young
BLitDDER CARCINOELt.., IN P!'-\TIENTS LESS THit~r
40
1
YEA.RS OLD
Clinical features Pt. Age 29 33 39 39
25 30
37 39 39 29 33 39
36 36*
37t 38* 38*· t
38t 38:j:
39 37:j:
39
Presenting Symptoms Unknown Hematuria Hematuria Hematuria Hematuria Irritation Unknown Hematuria Hematuria, irritation Hematuria Hematuria Hematuria Unknown Hematuria, irritation Calculi Hematuria, irritation Hematuria, irritation Hematuria, irritation Hematuria, irritation Subcutaneous mass Microhematuria Hematuria, irritiation
Duration of Symptoms (mos.) Unknown 36 36
6 2
Unknown Unknown 4 36 24 7 4 6 1 Unknown 24
Clinical Stage
Initial Treatment
Bladder Recurrence
C C
TUR§ TUR TUR TUR TUR TUR TUR TUR TUR TUR TUR Radical cystectomy Radical cystectomy Partial cystectomy
Unknown Multiple None 4 1 None 12 None None None None None None None
C C
5,000 rads, cystectomy 5,000 rads, cystectomy
None None
C Dl Dl D2 Unknown Unknown
5,000 rads, cystectomy Radiotherapy Radiotherapy Radiotherapy, partial cystectomy TUR Radiotherapy
None None None None None None
0 0 0 0 A A A A A
Bl Bl Bl
Cu:rrent Status (mos.)
Lost to followup Alive-338 Alive-18 Alive-130 Alive-123 Alive-6 Alive-110 Alive-21 Alive-11 Dead of disease- 17 Dead of disease-14 Dead of disease- 11 Dead with disease- 9 Dead without disease2 Dead with disease - 11 Dead without disease18 Dead with disease-11 Dead with disease- IO Dead with disease-15 Dead with disease- 5 Dead with disease-13 Dead with disease- 96
* Women. t Squamous carcinoma. :j: Adenocarcinoma. § TUR- transurethral resection.
patients with bladder carcinoma. A more thorough evaluation in these cases would appear to be indicated. Once the diagnosis has been established the extent of the disease should be assessed accurately and treatment should be instituted on the basis of the clinical stage. Therapy should be similar to that for older patients, according to the stage of disease. The aggressive and lethal potential of these tumors should dispel any thoughts of compromising therapy in younger patients by postponing necessary radical surgical procedures. The consequences of radical cystectomy, such as impotence, and the problems of urinary diversion may be exaggerated in young patients but they do not alter the need for such therapy. REFERENCES
1. Jewett, H.J.: Tumors of the bladder. In: Urology. Edited by M.
F. Campbell and J. H. Harrison. Philadelphia: W. B. Saunders Co., p. 1003, 1970. 2. Javadpour, N. and Mostofi, F. K: Primary epithelial tumors of
the bladder in the first two decades of life. J. Urol., 101: 706, 1969. 3. McGuire, E. J., Weiss, R. M. and Baskin, A. M.: Neoplasms of transitional cell origin in first twenty years oflife. Urolog-y, 1: 57, 1973.
4. McCarthy, J. P.: Transitional cell carcinoma of the bladder in the under 30 age group. Proc. Kimbrough Urol. Semin. 10: 47, 1975. 5. Mostofi, F. K.: Histologic Typing of Urinary Bladder Tumors. World Health Organization, 1973. 6. Jewett, H. J. and Strong, G. H.: Infiltrating carcinoma of the urinary bladder: diagnosis and clinical evaluation of curability. South. Med. J., 39: 203, 1946. 7. Fitch, L.B. and Rubenstone, A. I.: Carcinoma of the bladder in childhood. J. Urol., 87: 549, 1962. 8. Franzblau, A. H.: Bladder carcinoma in the young. Rocky Mountain Med. J., 65: 54, 1968. 9. Siegel, W. H. and Pincus, M. B.: Epithelial bladder tumors in children. J. Urol., 101: 55, 1969. 10. Benton, B. and Henderson, B. E.: Environmental exposure and bladder cancer in young males. J. Nat. Cancer Inst., 51: 269, 1973.
Vol. 120, August
Printed in U.SA.
CARCINOMA OF THE BLADDER IN PATIENTS LESS THAN 40 YEARS OLD D. E. JOHNSON
AND
S. HILLIS
From the Section of Urology, Department of Surgery, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas
ABSTRACT
The records were reviewed of 22 patients with bladder carcinoma before they were 40 years old to determine whether age alone influenced the course of the disease. There were 19 men and 3 women, reflecting a male predominance of 6 to 1. Of the 9 patients with superficial stage A/0 disease 8 are alive 6 months to 28 years after diagnosis, the remaining patient being lost to followup. The other 13 patients with tumors invading muscle are dead, 11 as a direct result of the disease. No evidence was found to substantiate earlier reports that bladder carcinoma in young patients has a more benign behavior. The incidence of bladder carcinoma increases with patient age, with the peak incidence being in the sixth decade oflife. 1 Although neoplasms are rare in patients less than 40 years old the available information suggests that the clinical course of vesical carcinoma is more benign in younger patients. Javadpour and Mostofi reviewed 40 cases of primary epithelial tumors of the bladder in patients less than 21 years old and found that the tumors were mostly transitional, papillary and non-infiltrating. 2 They also found that these tumors were of low grade malignancy, with a favorable prognosis. Likewise, McGuire and associates recently reported the benignity of the disease in their review of 62 patients with transitional cell carcinoma before the age of 21 years. 3 However, McCarthy refuted the belief that these tumors fail to recur by reporting a recurrence rate of 14 per cent in 79 cases of transitional cell carcinoma in patients less than 30 years old. 4 The recurrences frequently were more aggressive and more malignant. To better define the relationship between the biological potential of bladder carcinoma and the age of the patient we reviewed our experience with 22 patients less than 40 years old with proved vesical carcinoma. MATERIALS AND METHODS
The records were reviewed of 2,139 patients with malignant neoplasms of the bladder who were treated from March 1944 to September 1975. In 22 patients (1 per cent) epithelial carcinoma was diagnosed before they were 40 years old. In each case the diagnosis was confirmed by histologic review of the excised tissue. The lesions were classified and graded according to the recommendations of the World Health Organization. 5 Clinical staging of the disease, using endoscopy and palpable findings, was done in 21 cases according to Marshall's modification of the Jewett and Strong classification. 6 RESULTS
Clinical findings. There were 19 men and 3 women, reflecting a male predominance of about 6 to 1 (see table). Patient age at diagnosis ranged from 25 to 39 years, with an average of 35. 7 years. The most common symptom was gross hematuria (15 patients) with an irritable bladder as part of the symptom complex in 7 of the 15 patients. In 1 patient only symptoms of vesical irritability were present. In 1 instance each the lesion was found incidental to an evaluation for 1) microhematuria discovered at routine physical examination, Accepted for publication October 7, 1977. Read at annual meeting of Southeastern Section, American Urological Association, New Orleans, Louisiana, March 27-31, 1977. 172
2) urinary calculi and 3) metastatic subcutaneous mass. Presenting symptoms were not recorded in 3 cases. The mean duration from onset of symptoms to diagnosis was 6 months in the 17 cases in which this information had been recorded. Cystoscopic evaluation revealed exophytic (papillary) lesions in 10 patients, and endophytic (sessile) and solid-appearing lesions in 6 patients; the initial growth description of the tumor was not available in 6 patients. At diagnosis the lesions were staged O in 4 patients, A in 5, Bl in 3, C in 5, Dl in 2 and D2 in 1. In 2 patients the disease could not be assessed adequately at initial evaluation. The lesions were classified histologically as transitional cell carcinoma in 17 patients, squamous carcinoma in 3 and adenocarcinoma in 2. Treatment. Transurethral resections were done in 11 of the 12 cases of superficial disease (stages 0, A and Bl). Subsequently, recurrences were demonstrated in 4 of these patients. One patient with stage Bl disease underwent radical cystectomy with ileal conduit diversion. Treatment for patients with locally invasive disease (stage C) consisted of preoperative radiotherapy followed by cystectomy and ileal conduit diversion in 3 cases, partial cystectomy in 1 and radical cystectomy in 1. All 3 patients who had either regional metastases (stage Dl, 2 cases) or disseminated disease (stage D2, 1 case) received palliative radiotherapy directed to the primary tumor. Survival. Of the 9 patients with superficial stage 0/A disease 8 are known to be alive 6 months to 28 years after diagnosis, the remaining patient being lost to followup. The other 13 patients are dead, 11 as a direct result of the disease. The median survival time for this group was 11 months. DISCUSSION
The clinical features of vesical carcinoma differ little between patients less than 40 years old and those older. The only apparent differences are that patients less than 40 have less propensity for multifocal disease and reduced potential for recurrences, and the disease in this group occurs predominantly in men. 3 While previous investigators have suggested that epithelial neoplasms of the bladder in young patients are clinically and morphologically benign3 • 7- 9 infiltrating tumors have been reported, 5 the youngest patient being a 3-year-old girl. 3 Consequently, a diagnosis of bladder carcinoma should be considered in all patients with hematuria, regardless of age, and a thorough urological evaluation should be done. In reviewing 9 cases of vesical carcinoma in the young, Benton and Henderson found evidence in 6 to incriminate chemical carcinogens as an etiological factor. 10 Although our records preclude a definite statement regarding etiological factors chemical carcinogenesis should be suspected in young
BLitDDER CARCINOELt.., IN P!'-\TIENTS LESS THit~r
40
1
YEA.RS OLD
Clinical features Pt. Age 29 33 39 39
25 30
37 39 39 29 33 39
36 36*
37t 38* 38*· t
38t 38:j:
39 37:j:
39
Presenting Symptoms Unknown Hematuria Hematuria Hematuria Hematuria Irritation Unknown Hematuria Hematuria, irritation Hematuria Hematuria Hematuria Unknown Hematuria, irritation Calculi Hematuria, irritation Hematuria, irritation Hematuria, irritation Hematuria, irritation Subcutaneous mass Microhematuria Hematuria, irritiation
Duration of Symptoms (mos.) Unknown 36 36
6 2
Unknown Unknown 4 36 24 7 4 6 1 Unknown 24
Clinical Stage
Initial Treatment
Bladder Recurrence
C C
TUR§ TUR TUR TUR TUR TUR TUR TUR TUR TUR TUR Radical cystectomy Radical cystectomy Partial cystectomy
Unknown Multiple None 4 1 None 12 None None None None None None None
C C
5,000 rads, cystectomy 5,000 rads, cystectomy
None None
C Dl Dl D2 Unknown Unknown
5,000 rads, cystectomy Radiotherapy Radiotherapy Radiotherapy, partial cystectomy TUR Radiotherapy
None None None None None None
0 0 0 0 A A A A A
Bl Bl Bl
Cu:rrent Status (mos.)
Lost to followup Alive-338 Alive-18 Alive-130 Alive-123 Alive-6 Alive-110 Alive-21 Alive-11 Dead of disease- 17 Dead of disease-14 Dead of disease- 11 Dead with disease- 9 Dead without disease2 Dead with disease - 11 Dead without disease18 Dead with disease-11 Dead with disease- IO Dead with disease-15 Dead with disease- 5 Dead with disease-13 Dead with disease- 96
* Women. t Squamous carcinoma. :j: Adenocarcinoma. § TUR- transurethral resection.
patients with bladder carcinoma. A more thorough evaluation in these cases would appear to be indicated. Once the diagnosis has been established the extent of the disease should be assessed accurately and treatment should be instituted on the basis of the clinical stage. Therapy should be similar to that for older patients, according to the stage of disease. The aggressive and lethal potential of these tumors should dispel any thoughts of compromising therapy in younger patients by postponing necessary radical surgical procedures. The consequences of radical cystectomy, such as impotence, and the problems of urinary diversion may be exaggerated in young patients but they do not alter the need for such therapy. REFERENCES
1. Jewett, H.J.: Tumors of the bladder. In: Urology. Edited by M.
F. Campbell and J. H. Harrison. Philadelphia: W. B. Saunders Co., p. 1003, 1970. 2. Javadpour, N. and Mostofi, F. K: Primary epithelial tumors of
the bladder in the first two decades of life. J. Urol., 101: 706, 1969. 3. McGuire, E. J., Weiss, R. M. and Baskin, A. M.: Neoplasms of transitional cell origin in first twenty years oflife. Urolog-y, 1: 57, 1973.
4. McCarthy, J. P.: Transitional cell carcinoma of the bladder in the under 30 age group. Proc. Kimbrough Urol. Semin. 10: 47, 1975. 5. Mostofi, F. K.: Histologic Typing of Urinary Bladder Tumors. World Health Organization, 1973. 6. Jewett, H. J. and Strong, G. H.: Infiltrating carcinoma of the urinary bladder: diagnosis and clinical evaluation of curability. South. Med. J., 39: 203, 1946. 7. Fitch, L.B. and Rubenstone, A. I.: Carcinoma of the bladder in childhood. J. Urol., 87: 549, 1962. 8. Franzblau, A. H.: Bladder carcinoma in the young. Rocky Mountain Med. J., 65: 54, 1968. 9. Siegel, W. H. and Pincus, M. B.: Epithelial bladder tumors in children. J. Urol., 101: 55, 1969. 10. Benton, B. and Henderson, B. E.: Environmental exposure and bladder cancer in young males. J. Nat. Cancer Inst., 51: 269, 1973.