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Bipedal lymphography in the management of bladder cancer
ClinicalRadiology ( 1980) 31, 555 -558
0009-9260/80/01020555502.00
© 1980 Royal Collegeof Radiologists
Bipedal Lymphography in the Management of Bladder Cancer ALAN RODGER, S. ROGER WILD and WILLIAM DUNCAN
Department of Radiodiagnosis and Radiotherapy, University of Edinburgh, Western General Hospital, Edinburgh Bipedal lymphography was performed in 91 patients with transitional cell carcinoma of the bladder. Equivocal reports were submitted in 18 (19.8%) examinations. In this series 18 (19.8%) of the patients died within one year of first treatment by radical radiotherapy. The prognosis was poorer in patients with more locally advanced tumours, in whom there was a higher proportion of abnormal lymphograms. An abnormal lymphogram was also related to a poorer prognosis than if the lymphogram was normal. This difference was greater when associated with a poorly differentiated cancer. The implications for management are discussed.
The initial examination and investigation of a patient with bladder cancer is directed towards obtaining a diagnosis, delineating the extent and spread of disease and selecting the best form of management. Various prognostic indices determined by this initial assessment will influence this final decision on treatment (Cooper and Smith, 1975). The most important is cystoscopic examination under full anaesthesia to determine the nature of the tumour, the extent of epithelial involvement and the degree of local infiltration. The rich lymphatic network of the bladder suggests that tumour cells may readily metastasise to the local lymphatics (Wirtanen and Miller, 1973). Lymphography may give useful information related to possible lymphatic spread of these cancers (Viamonte et al., 1962), and it has been suggested that lymphography is essential in planning the treatment of infiltrating bladder cancers (Turner et al., 1976). This review has been undertaken to determine if lymphographic findings have a prognostic value in patients undergoing small field radiotherapy for bladder cancer.
METHODS The patients reviewed were all referred for consideration for radiotherapy for histologically proven transitional cell carcinoma of the bladder to the Department of Radiation Ontology at the Western General Hospital and at the Royal Infirmary of Edinburgh. The 267 patients considered were first registered in that department between January 1974 and December 1976. All underwent at least cystoscopy and full pelvic examination under general anaesthesia, and their tumours were staged locally by
Table 1 - Local staging of bladder cancer Stage I Stage II Stage III Stage IV
Primary tumour involvingepithelium and submucosa only Primary tumour invading bladder muscle but not penetrating the bladder wall Primary tumour penetrating through the bladder wall but remaining mobile and not involving other organs Primary tumour fixed to pelvicwall or invading neighbouring organs
the system adopted by the British Association of Urological Surgeons (Wallace, 1956) (Table 1). During these three years, bipedal lymphography was increasingly performed as a pre-treatment investigation. It was attempted in 111 of the 267 patients, and was successful in 107, of whom six were only unilaterally successful. Sixteen of those undergoing successful lymphography were subsequently excluded from this review, in 12 because only palliative treatment could be offered, and in four because of inadequate histological data. Thus 91 patients with histologically confirmed transitional cell carcinomas suitable for radical radiotherapy were subjected to detailed review. Of these nine underwent cystectomy within one year of completing radiotherapy. RADIOLOGICAL EXAMINATION Bipedal lymphography was performed using the method described by Macdonald and Wallace (1965). The most medial interdigital web of each foot was injected with 0.5 ml of a mixture of 1% (1 ml) lignocaine and 1 ml patent blue violet, as this gave the best
556
CLINICAL R A D I O L O G Y
visuallsation of a lymphatic overlying the first metatarsal. Most patients received 13ml of 'Lipiodol Ultrafluid' and less if there was any history of preexisting lung disease. Wound infections, which were all minor, were seen in only two of the original 107 successfully investigated patients, in whom a further two patients developed pulmonary complications. These latter two patients both had locally Stage 1V disease. It became evident that patients with locally very advanced disease were more prone to develop pulmonary complications. This may have been due to contrast medium bypassing obstructed pelvic nodes to spill over into the lungs, as suggested by Bron et al. (1963). Therefore, routine lymphography in Stage IV patients was discontinued. There were, however, no complications in the 91 patients reviewed, and in particular no allergic reactions were seen. The radiographs of the 91 patients were reviewed by one consultant radiologist (S.R.W.). When available, follow-up films were included in the assessment. In 18 cases the radiological conclusions were equivocal (19.8%) and these were categorised as either equivocal but likely to be positive in 10 patients; or equivocal but likely to be negative in eight patients (Table 2).
RESULTS Staging and Histology
Although all patients reviewed had transitional cell carcinomas, the histological sections have not been reviewed by a single pathologist. Tumours described as well-differentiated and moderately well-differen. tiated have been grouped together in the survey as 'differentiated' cancers, while those described as poorly differentiated or anaplastic or with features suggesting lack of differentiation have been grouped as 'poorly differentiated' cancers. Sixty-two of the 91 patients had 'differentiated, transitional cell carcinomas, and 29 had 'poorly differentiated' tumours. Table 3 describes the distri. bution of histological type by clinical stage. Patients with early Stage I disease have a small proportion of 'poorly differentiated' tumours (18.5%)as might be expected, while the numbers of 'poorly differen. tiated' tumours increase with the local stage of disease. In all, 18 of these 91 patients (19.8%)died within 12 months of commencing radiotherapy. When mortality is compared with clinical stage (Table 4), it is clear that in this series of patients the prognosis is progressively worse with advancing local disease. Table 4 - Clinical stage and prognosis
Table 2 - Lymphography reporting
Clinical stage Number
Report
Equivocal
Unequivocal
Total
Abnormal Normal Total
10 8 18 (19.8%)
24 49 73 (80.2%)
34 57 91 (100%)
It was considered that if management was subsequently to be influenced by lymphographic staging, equivocal reporting should be discouraged. Therefore, in the final analysis 'equivocal-positive' were grouped with definitely positive results and 'equivocal-negative' with the negative reports.
Dead at 12 months
I
27
1 (3.7%)
II III Total
43 21 91
10 (23%) 7 (33%) 18 (19.8%)
Lymphographic Results
Normal lymphograms were reported in 57 out of the 91 patients (62.6%). It is interesting that in this series there is no correlation between the histological differentiation of the primary cancer and the lymphographic findings (Table 5).
Table 3 - Histologicalgrade and clinical stage Histological grade
'Differentiated' cancer 'Poorly differentiated' cancer Total
Total
Clinical stage I
H
III
22 (81.5%) 5 (18.5%) 27
27 (62.8%) 16 (37.2%) 43
13 (61.9%) 8 (38.1%) 21
62 (68%) 29 (32%) 91
BIPEDAL LYMPHOGRAPHY IN THE MANAGEMENT OF BLADDER CANCER
Table 8 - Prognosis by clinical stage and lymphogram report
Table 5 - Histological grade and lymphogram report Histological grade
,l)ifferentiated cancers ,poorly differentiated' cancers Total
L ymphogram report
557
Total
Normal
Abnormal
40 (64.5%)
22 (35.5%)
62
17 (58.6%) 57
12 (41.4%) 34
29 91
Clinical stage
I II III Total
Lymphogram report Normal
Abnormal
Number Dead at 12 months
Number Deat at 12 months
20 26 11 57
7 17 10 34
0 6 (23%) 3 (27%) 9 (15.8%)
1 (14%) 4 (23.5%) 4 (40%) 9 (26.5%)
Table 6 - Clinical stage and lymphogram report Clinical stage
Normal
I
II III Total
Total
L ymphogram report
20 (74%)
26 (60.5%) 11 (52.4%) 57
Abnormal
7 (26%)
17 (39.5%) 10 (47.6%) 34
27 43 21 91
(Table 8) suggests that locally advanced tumours in the presence of an abnormal lymphogram confer a very poor prognosis. Forty per cent o f patients with Stage III tumours and an abnormal lymphogram died within a year of treatment.
DISCUSSION
When lymphography is compared with clinical stage (Table 6), the proportion with an abnormal lymphogram increases as the clinical stage becomes more advanced. If the lymphographic results is taken as a prognostic index (Table 7), it is seen that only 15.8% of those with normal lymphograms died within 12 months of first treatment, compared with 26.5% of those with abnormal lymphographic findings, and this difference is statistically significant ( P < 0.05). Table 7 also confirms that an extremely bad prognosis is found in patients with both an abnormal lymphogram and a poorly differentiated tumour, 33.3% of whom died within one year of treatment. An analysis of the effect of the lymphographic findings and the local extent of tumour on survival
An attempt has been made in a series o f patients with transitional cell carcinoma of the bladder to relate the lymphographic findings to prognosis, assessed by survival one year after commencing radical radiotherapy. The radiotherapy technique was not influenced by lymphographic results, and in this series treatment was not directed to include the lymphatic drainage area. Although the results reflect only crude survival at one year, and do not take into account local response of the primary tumour to treatment, prognosis is seen to correlate well with lymphographic findings, even in the absence of histological proof of node infiltration. It would seem logical in patients with abnormal lymphograms to advocate further treatment to the lymphatic drainage area, either by extended field radiotherapy or by lymphadenectomy, in order to
Table 7 - Prognosis by histological grade and lymphogram report Histological grade
'Differentiated' cancers 'Poorly differentiated' cancers Total
L ymphogram report Normal
Abnormal
Number Dead at 12 months
Number Dead at 12 months
40 17 57
22 12 34
7 (17.5%) 2 (11.8%) 9 (15.8%)
5 (22.7%) 4 (33.3%) 9 (26.5%)
558
CLINICAL RADIOLOGY
improve survival rates. The addition of cytotoxic chemotherapy is now also considered indicated in patients who also have poorly differentiated tumours. It is essential therefore to obtain a definite radiological report as part of the pretreatment assessment so that o p t i m u m management may be decided. Equivocal reports seen in l 3.2% o f reports in different series (Turner et al., 1976; Muir et al., 1978), are unhelpful to those responsible for management, and treatment cannot reasonably be delayed until followup is performed. 'Judicious guessing', as to whether the appearances are considered more likely to be negative or positive, should be encouraged in the group o f patients when an experienced radiologist has genuine doubts about the significance o f lymphographic appearances. Bipedal lymphography is a valuable investigation in the assessment o f bladder cancer and o f importance in determining its management. Lymphography has a significant influence on prognosis and it may help to improve the results of management b y indicating when involvement o f regional l y m p h nodes should influence treatment policy.
REFERENCES
Bron, K. M., Baum, S. & Abrams, H. L. (1963). Oil enlbolis,, in lymphangiography. Radiology, 80, 194- 202. "" Cooper, E. H. & Smith, P. (1975). Bladder cancer: prognostic factors and assessment of response to treatment. In Cancer Therapy: Prognostic Factors and Criteria of Response, ed. Staquet, M. J. Raven Press, New York. Macdonald, J. S. & Wallace, E. N. K. (1965). Lymphangio. graphy in tumours of the kidney, bladder, and testicle. British Journal of Radiology, 38, 93-99. Muir, B. B., Sinclair, D. J. & Duncan, W. (1978). The role of radiology in the assessment of bladder cancer. Clinical Radiology, 29, 479-485. Turner, A. G., Hendry, W. F., Macdonald, J. S. & Wallace, D. M. (1976). The value of lymphography in the manage. ment of bladder cancer. British Journal of Urology 48, 579-586. Viamonte, M., Myers, M. B., Sotto, M., Kenyon, N. M. & Parks, R. E. (1962) Lymphography: its role in the detec. tion and therapeutic evaluation of carcinoma and neo. plastic conditions of the genitourinary tract. Journal of Urology, 87, 85-90. Wallace, D. M. (1956) The natural history and possible causes of bladder tumours. Annals of the Royal College of Surgeons, 18, 366-383. Wirtanen, G. W. & Miller, R. C. (1973). Bladder lymphatics and tumour dissemination. Journal of Urology, 109, 5859.
0009-9260/80/01020555502.00
© 1980 Royal Collegeof Radiologists
Bipedal Lymphography in the Management of Bladder Cancer ALAN RODGER, S. ROGER WILD and WILLIAM DUNCAN
Department of Radiodiagnosis and Radiotherapy, University of Edinburgh, Western General Hospital, Edinburgh Bipedal lymphography was performed in 91 patients with transitional cell carcinoma of the bladder. Equivocal reports were submitted in 18 (19.8%) examinations. In this series 18 (19.8%) of the patients died within one year of first treatment by radical radiotherapy. The prognosis was poorer in patients with more locally advanced tumours, in whom there was a higher proportion of abnormal lymphograms. An abnormal lymphogram was also related to a poorer prognosis than if the lymphogram was normal. This difference was greater when associated with a poorly differentiated cancer. The implications for management are discussed.
The initial examination and investigation of a patient with bladder cancer is directed towards obtaining a diagnosis, delineating the extent and spread of disease and selecting the best form of management. Various prognostic indices determined by this initial assessment will influence this final decision on treatment (Cooper and Smith, 1975). The most important is cystoscopic examination under full anaesthesia to determine the nature of the tumour, the extent of epithelial involvement and the degree of local infiltration. The rich lymphatic network of the bladder suggests that tumour cells may readily metastasise to the local lymphatics (Wirtanen and Miller, 1973). Lymphography may give useful information related to possible lymphatic spread of these cancers (Viamonte et al., 1962), and it has been suggested that lymphography is essential in planning the treatment of infiltrating bladder cancers (Turner et al., 1976). This review has been undertaken to determine if lymphographic findings have a prognostic value in patients undergoing small field radiotherapy for bladder cancer.
METHODS The patients reviewed were all referred for consideration for radiotherapy for histologically proven transitional cell carcinoma of the bladder to the Department of Radiation Ontology at the Western General Hospital and at the Royal Infirmary of Edinburgh. The 267 patients considered were first registered in that department between January 1974 and December 1976. All underwent at least cystoscopy and full pelvic examination under general anaesthesia, and their tumours were staged locally by
Table 1 - Local staging of bladder cancer Stage I Stage II Stage III Stage IV
Primary tumour involvingepithelium and submucosa only Primary tumour invading bladder muscle but not penetrating the bladder wall Primary tumour penetrating through the bladder wall but remaining mobile and not involving other organs Primary tumour fixed to pelvicwall or invading neighbouring organs
the system adopted by the British Association of Urological Surgeons (Wallace, 1956) (Table 1). During these three years, bipedal lymphography was increasingly performed as a pre-treatment investigation. It was attempted in 111 of the 267 patients, and was successful in 107, of whom six were only unilaterally successful. Sixteen of those undergoing successful lymphography were subsequently excluded from this review, in 12 because only palliative treatment could be offered, and in four because of inadequate histological data. Thus 91 patients with histologically confirmed transitional cell carcinomas suitable for radical radiotherapy were subjected to detailed review. Of these nine underwent cystectomy within one year of completing radiotherapy. RADIOLOGICAL EXAMINATION Bipedal lymphography was performed using the method described by Macdonald and Wallace (1965). The most medial interdigital web of each foot was injected with 0.5 ml of a mixture of 1% (1 ml) lignocaine and 1 ml patent blue violet, as this gave the best
556
CLINICAL R A D I O L O G Y
visuallsation of a lymphatic overlying the first metatarsal. Most patients received 13ml of 'Lipiodol Ultrafluid' and less if there was any history of preexisting lung disease. Wound infections, which were all minor, were seen in only two of the original 107 successfully investigated patients, in whom a further two patients developed pulmonary complications. These latter two patients both had locally Stage 1V disease. It became evident that patients with locally very advanced disease were more prone to develop pulmonary complications. This may have been due to contrast medium bypassing obstructed pelvic nodes to spill over into the lungs, as suggested by Bron et al. (1963). Therefore, routine lymphography in Stage IV patients was discontinued. There were, however, no complications in the 91 patients reviewed, and in particular no allergic reactions were seen. The radiographs of the 91 patients were reviewed by one consultant radiologist (S.R.W.). When available, follow-up films were included in the assessment. In 18 cases the radiological conclusions were equivocal (19.8%) and these were categorised as either equivocal but likely to be positive in 10 patients; or equivocal but likely to be negative in eight patients (Table 2).
RESULTS Staging and Histology
Although all patients reviewed had transitional cell carcinomas, the histological sections have not been reviewed by a single pathologist. Tumours described as well-differentiated and moderately well-differen. tiated have been grouped together in the survey as 'differentiated' cancers, while those described as poorly differentiated or anaplastic or with features suggesting lack of differentiation have been grouped as 'poorly differentiated' cancers. Sixty-two of the 91 patients had 'differentiated, transitional cell carcinomas, and 29 had 'poorly differentiated' tumours. Table 3 describes the distri. bution of histological type by clinical stage. Patients with early Stage I disease have a small proportion of 'poorly differentiated' tumours (18.5%)as might be expected, while the numbers of 'poorly differen. tiated' tumours increase with the local stage of disease. In all, 18 of these 91 patients (19.8%)died within 12 months of commencing radiotherapy. When mortality is compared with clinical stage (Table 4), it is clear that in this series of patients the prognosis is progressively worse with advancing local disease. Table 4 - Clinical stage and prognosis
Table 2 - Lymphography reporting
Clinical stage Number
Report
Equivocal
Unequivocal
Total
Abnormal Normal Total
10 8 18 (19.8%)
24 49 73 (80.2%)
34 57 91 (100%)
It was considered that if management was subsequently to be influenced by lymphographic staging, equivocal reporting should be discouraged. Therefore, in the final analysis 'equivocal-positive' were grouped with definitely positive results and 'equivocal-negative' with the negative reports.
Dead at 12 months
I
27
1 (3.7%)
II III Total
43 21 91
10 (23%) 7 (33%) 18 (19.8%)
Lymphographic Results
Normal lymphograms were reported in 57 out of the 91 patients (62.6%). It is interesting that in this series there is no correlation between the histological differentiation of the primary cancer and the lymphographic findings (Table 5).
Table 3 - Histologicalgrade and clinical stage Histological grade
'Differentiated' cancer 'Poorly differentiated' cancer Total
Total
Clinical stage I
H
III
22 (81.5%) 5 (18.5%) 27
27 (62.8%) 16 (37.2%) 43
13 (61.9%) 8 (38.1%) 21
62 (68%) 29 (32%) 91
BIPEDAL LYMPHOGRAPHY IN THE MANAGEMENT OF BLADDER CANCER
Table 8 - Prognosis by clinical stage and lymphogram report
Table 5 - Histological grade and lymphogram report Histological grade
,l)ifferentiated cancers ,poorly differentiated' cancers Total
L ymphogram report
557
Total
Normal
Abnormal
40 (64.5%)
22 (35.5%)
62
17 (58.6%) 57
12 (41.4%) 34
29 91
Clinical stage
I II III Total
Lymphogram report Normal
Abnormal
Number Dead at 12 months
Number Deat at 12 months
20 26 11 57
7 17 10 34
0 6 (23%) 3 (27%) 9 (15.8%)
1 (14%) 4 (23.5%) 4 (40%) 9 (26.5%)
Table 6 - Clinical stage and lymphogram report Clinical stage
Normal
I
II III Total
Total
L ymphogram report
20 (74%)
26 (60.5%) 11 (52.4%) 57
Abnormal
7 (26%)
17 (39.5%) 10 (47.6%) 34
27 43 21 91
(Table 8) suggests that locally advanced tumours in the presence of an abnormal lymphogram confer a very poor prognosis. Forty per cent o f patients with Stage III tumours and an abnormal lymphogram died within a year of treatment.
DISCUSSION
When lymphography is compared with clinical stage (Table 6), the proportion with an abnormal lymphogram increases as the clinical stage becomes more advanced. If the lymphographic results is taken as a prognostic index (Table 7), it is seen that only 15.8% of those with normal lymphograms died within 12 months of first treatment, compared with 26.5% of those with abnormal lymphographic findings, and this difference is statistically significant ( P < 0.05). Table 7 also confirms that an extremely bad prognosis is found in patients with both an abnormal lymphogram and a poorly differentiated tumour, 33.3% of whom died within one year of treatment. An analysis of the effect of the lymphographic findings and the local extent of tumour on survival
An attempt has been made in a series o f patients with transitional cell carcinoma of the bladder to relate the lymphographic findings to prognosis, assessed by survival one year after commencing radical radiotherapy. The radiotherapy technique was not influenced by lymphographic results, and in this series treatment was not directed to include the lymphatic drainage area. Although the results reflect only crude survival at one year, and do not take into account local response of the primary tumour to treatment, prognosis is seen to correlate well with lymphographic findings, even in the absence of histological proof of node infiltration. It would seem logical in patients with abnormal lymphograms to advocate further treatment to the lymphatic drainage area, either by extended field radiotherapy or by lymphadenectomy, in order to
Table 7 - Prognosis by histological grade and lymphogram report Histological grade
'Differentiated' cancers 'Poorly differentiated' cancers Total
L ymphogram report Normal
Abnormal
Number Dead at 12 months
Number Dead at 12 months
40 17 57
22 12 34
7 (17.5%) 2 (11.8%) 9 (15.8%)
5 (22.7%) 4 (33.3%) 9 (26.5%)
558
CLINICAL RADIOLOGY
improve survival rates. The addition of cytotoxic chemotherapy is now also considered indicated in patients who also have poorly differentiated tumours. It is essential therefore to obtain a definite radiological report as part of the pretreatment assessment so that o p t i m u m management may be decided. Equivocal reports seen in l 3.2% o f reports in different series (Turner et al., 1976; Muir et al., 1978), are unhelpful to those responsible for management, and treatment cannot reasonably be delayed until followup is performed. 'Judicious guessing', as to whether the appearances are considered more likely to be negative or positive, should be encouraged in the group o f patients when an experienced radiologist has genuine doubts about the significance o f lymphographic appearances. Bipedal lymphography is a valuable investigation in the assessment o f bladder cancer and o f importance in determining its management. Lymphography has a significant influence on prognosis and it may help to improve the results of management b y indicating when involvement o f regional l y m p h nodes should influence treatment policy.
REFERENCES
Bron, K. M., Baum, S. & Abrams, H. L. (1963). Oil enlbolis,, in lymphangiography. Radiology, 80, 194- 202. "" Cooper, E. H. & Smith, P. (1975). Bladder cancer: prognostic factors and assessment of response to treatment. In Cancer Therapy: Prognostic Factors and Criteria of Response, ed. Staquet, M. J. Raven Press, New York. Macdonald, J. S. & Wallace, E. N. K. (1965). Lymphangio. graphy in tumours of the kidney, bladder, and testicle. British Journal of Radiology, 38, 93-99. Muir, B. B., Sinclair, D. J. & Duncan, W. (1978). The role of radiology in the assessment of bladder cancer. Clinical Radiology, 29, 479-485. Turner, A. G., Hendry, W. F., Macdonald, J. S. & Wallace, D. M. (1976). The value of lymphography in the manage. ment of bladder cancer. British Journal of Urology 48, 579-586. Viamonte, M., Myers, M. B., Sotto, M., Kenyon, N. M. & Parks, R. E. (1962) Lymphography: its role in the detec. tion and therapeutic evaluation of carcinoma and neo. plastic conditions of the genitourinary tract. Journal of Urology, 87, 85-90. Wallace, D. M. (1956) The natural history and possible causes of bladder tumours. Annals of the Royal College of Surgeons, 18, 366-383. Wirtanen, G. W. & Miller, R. C. (1973). Bladder lymphatics and tumour dissemination. Journal of Urology, 109, 5859.