Results of testicular tumour management based on lymphographic staging

ClinicalRadiology (1981) 32, 683-686

0009-9260/81/01140683802.00

© 1981 Royal College of Radiologists

Results of Testicular Tumour Management Based on Lymphographic Staging M. E. HOLMES

Weston Park Hospital, Whitham Road, SheffieM The results of the treatment of germ cell tumours of the testis between 1968 and 1975 are presented and assessed in relation to lymphographic staging. The number of patients seen was 132. The four year disease-free survival for Stage I seminoma was 100% and for Stage II 84% and for Stage I teratoma 72% and Stage II 31%. In Stage II seminoma supra diaphragmatic node metastases were only seen where node metastases had caused renal or ureteric displacement, and a case is made for selective prophylactic radiotherapy above the diaphragm. There was a relapse rate of 24% in the para-aortic nodes of Stage I teratomas where prophylactic irradiation was not given, suggesting a high incidence of occult metastases.

Testicular tumours account for only 1% of male malignancies but assume importance because of the age range affected and they offer a challenge to treatment as the majority can now be considered potentially curable. The optimum treatment for each stage of the disease, either seminoma or teratoma, remains under discussion and trial, but always based on the interpretative findings of the various investigations. Lymphography has been considered an important investigation in the management of these tumours for over a decade but it may not influence the curability of the disease. This paper reviews all the germ cell tumours treated at Weston Park Hospital between 1968 and 1975. Routine post-orchidectomy lymphography began in 1968 and in the following seven years nearly all the tumours were treated by a standard protocol which has enabled an assessment of the treatment in relation to the lymphographic findings. This series provides a follow-up period of 4 - 1 1 years which can be equated to cure as no patient relapsed after a four year posttreatment period. MATERIALS AND METHODS Only those patients with germ cell tumours have been included in this series, and these account for the majority, seen. In this eight year period 132 new cases were referred (Table 1). The proportion of seminomas varies in published series from 34 to 55% (Kuhn and Johnson, 1972). The age range is given in Table 2. There were two instances of second malignancies in the remaining testis, both were second seminomas, one occurring after two and a half years and the other after four years. Both had normal repeat lymphograms and remain alive and disease-free without further

treatment. This incidence was 1.5%. Investigations following inguinal orchidectomy included chest radiograph, lymphography and intravenous urography (IVU), full blood count, urea and electrolytes and liver function tests. Alpha-feto protein and betaHCG were not available during this study period. Staging was as described in Table 3. Staging for seminoma and teratoma is shown in Tables 4 - 6 . Six Table 1 - Testiculat number 132)

germinal tumours 1968-75

Seminomas Teratomas Mixed

(total

72 (55%) 52 (39%) 8 (6%)

Table 2 - Age range (yeats) Seminoma Teratoma

19-71, mean 41 19-69, mean 34

Table 3 - Staging I II III IV

Tumour confined to testis Involvement of abdominal lymph nodes and/or involvement of cord Involvement of supradiaphragmatic nodes Widespreadmetastases

Table 4 - Seminoma staging I II III IV

28 (42.5%) 32 (48.5%) 2 (3%) 4 (6%)

Total

66

(100%)

684

CLINICAL

Table 5 - Teratoma staging (I)

RADIOLOGY

Table 7 - Treatment policy - seminoma

I

25

II

(48%)

Stages I and II

Post-orchidectomy irradiation to paraaortic nodes and ipsilateral iliac nodes or whole pelvis 3500 cGy/20 fractions/four weeks (8 MeV)

Stage III

As above plus irradiation to chest 2000 cGy/15 fractions/three weeks to whole thorax, midline dose parallel opposed fields, uncorrected for lung transmission + 1500 cGy/10 fractions/ two weeks to mediastinum and supraclavicular regions, midline dose parallel opposed fields

Stage IV

Radiotherapy and cytotoxic therapy

16 (31%)

IIl

1

(2%)

IV

10 (19%)

Total

52 (100%)

Table 6 - Teratoma staging (II) Stage Differ- InterUndiffer- Tropho- Unclassi- Total entiated mediate entiated blastic fled I

-

II

1

13 5

11 3

III

-

-

-

IV

-

3

2

Total 1

21

16

2

25 16

-

1

1

6

1

-

-

5

10

Table 8 - Treatment policy - teratoma

12

52

Stage I

Orchidectomy only

Stages II and III

Originally cytotoxic therapy - single agent actinomycin D. Recently po~torchidectomy irradiation to para-aortic and ipsilateral iliac nodes 4500 cGy/ 20 fractions/four weeks (8 MeV) plus mediastinal and supraclavieular node irradiation. 4000 cGy/20 fractions/ four weeks

Stage IV

Cytotoxic chemotherapy

1

of the seminoma cases did not have lymphograms and were not accurately staged. These have not been included in the assessment. Without lymphographic findings accurate staging is not possible. Early studies without this investigation show low proportions o f Stage II disease in seminoma such as 15% b y Blandy et al. (1970) and 23% by Castro (1972), although Smithers et al. (1971) reported a 31% incidence with lymphographic findings. Again the staging for teratomas is at variance with other series such as 7% Stage II (Blandy et al., 1970). However, a recent review from the Royal Marsden (Tyrrell and Peckham, 1976), where lymphographic staging was employed, reported an incidence of 15% Stage II and 32% Stage IV, which may reflect the result of selective referral to a testicular unit. It is apparent that without lymphography the majority of testicular tumours are understaged as only rarely are abdominal nodes palpable or is displacement seen on intravenous urography (IVU). TREATMENT Treatment policies during this period are shown in Tables 7 and 8. Radiation dosage is the midline dose from the use of a parallel pair o f opposed fields. Treatment for seminomas was modified slightly over this period b y reduction o f the radiation fields to include only the para-aortic and ipsilateral iliac nodes, as demonstrated from the lymphogram. It was considered that teratomas were not sufficiently radiosensitive to warrant prophylactic irradiation, so Stage I tumours were left on a 'watch' policy, with monthly follow-up lymphogram films. Although post-operative irradiation is generally considered

necessary for Stage I teratomas there is now a resurgence of adoption o f a watch policy using tumour markers as a guide for activity o f disease. Cytotoxic

Therapy

Up to 1974 patients with Stage II teratoma were treated post-operatively with a course of actinomycinD given in a dose o f 0.05 mg/kg b o d y weight, divided into three daily intravenous doses and repeated every six weeks to a total o f 10 courses. A similar regime was given to patients with relapsed or metastatic disease. F r o m 1974 onwards patients with Stage II teratoma were given radiotherapy post-operatively and cytotoxics were given only to patients with metastatic disease. The following regime was given intravenously every three weeks for as long as a response was achieved, with a minimum of three courses. Vinblastine, 6 mg/m 2 Actinomycin D, 1 mg/m 2 Adriamycin, 20 mg/m 2 Very few patients with seminoma were treated with cytotoxics. Drugs used included single agent therapy

TESTICULAR

TUMOUR

Table 9 - Results - Seminoma - four year survival

AU stages Stage I II III IV Unstaged

685

MANAGEMENT

Table 11 - Results - Teratoma - four year crude survival

Crude

Corrected

Stage

55/72 (76%)

57/72 (79%)

27/28 (96%) 25/32 (78%) 0/2 0/4 3/6

28/28 (100%) 27/32 (84%) 1/2 0/4 4/6

I 18/25 (72%) 9/12.(75%) II 5/16 (31%) III and IV 0/11 (0%) All stages 23/52 (44%)

All groups

T.intermediate

T.undifferentiated

5/9 (55%)

Table 12 - Tetatoma Stage I relapses Site o f relapse

Type

Table 10 - Seminoma Stage II relapses Site o f relapse

Time interval (months)

Current status

Right supraclavicular Paratracheal Lung Para-aortic Para-aortic Mediastinum Lung

12 12 12 9 15 12 12

D A D D D A D

Para-aortic Lung Lung Para-aortic Lung Para-aortic Para-aortic Para-aortic Para-aortic

I U U I U U I U I

Time interval (months)

Current status

24 12 6 2 3 1 8 9 6

D D D A D D D D A

I - intermediate; U = undifferentiated; D = dead; A = alive. D, dead; A, alive. with actinomycin D, as for teratoma, and also cyclophosphamide given as 1 g intravenously on three consecutive days and repeated monthiy.

RESULTS Table 9 shows the four year disease-free survival figures for seminoma. The corrected figures exclude those patients dying o f unrelated disease. The overall survival for all stages was 74%. There were no relapses in patients with Stage I disease, but o f those with Stage II disease there were five deaths from seminoma and two patients relapsed but were successfully retreated. Table 10 details these relapses. Only three patients relapsed in the mediastinum or supraclavicular region and these three were the only ones who had abnormalities o f the IVU as well as lymphographic changes. (One right ureteric obstruction, one right ureteric displacement, one obstructed right kidney.) One of these patients died from liver metastases and the other two remain alive and diseasefree after four years following further irradiation. Of the rerfiaining Stage II seminomas who relapsed, two developed pulmonary metastases and died despite pulmonary irradiation, another patient developed skin and bone metastases despite apparent local control o f para-aortic recurrence, and the other presented with inguinal node involvement and normal testes and died with local recurrence and distant metastases.

Table 11 shows the four year disease-free survival for teratomas with a 72% four year survival for Stage I, only two of which had post-operative radiotherapy and neither of which relapsed. In this series of untreated patients there were nine relapses, three pulmonary, an incidence of 12% and six in the para-aortic region, an incidence o f 24%. These are detailed in Table 12. Two patients were successfully treated by radiotherapy but the remainder died despite treatment with radiotherapy and cytotoxics. There is a suggestion that the undifferentiated tumours relapse with blood-borne metastases while intermediate tumours relapse from lymphatic metastases. Of the Stage II patients the only survivors were those who received irradiation and one who underwent retroperitoneal node dissection. Of those metastasising outside the abdomen five developed pulmonary metastases and two developed left supraclavicular node deposits with rapid development of pulmonary metastases. No patients with either teratoma or seminoma treated with cytotoxic agents for either metastatic disease or as primary management for Stage II teratoma achieved remission o f their disease. Only four patients were treated with the vincristine, adriamycin, actinomycin D combination within this study period and the regime was replaced in 1976 by a bleomycin/vinblastine combination. There were too few mixed tumours for detailed analysis.

686 DISCUSSION

CLINICAL

RADIOLOGY

tion is justified when it is highly probable that such deposits can be sterilised. With the availability of measuring facilities for alpha-feto protein and beta-HCG and the high correlation between raised levels and active disease a 'watch' policy is easier to follow, especially where there are raised levels prior to orchidectomy. However, many patients are still being referred, particularly from peripheral hospitals, without these pre-operative investigations. With the knowledge that not all turnouts secrete one or another of these markers it is not possible to predict the safety of a watch policy. Salvage with cytotoxic therapy and irradiation is much improved, but nodal disease once advanced is less likely to be cured than pulmonary disease. Results of further studies of careful follow-up of such patients are needed for evaluation of the use of these markers in early stage disease. In Stage II disease radiotherapy can control paraaortic disease but with large node deposits the chances become less (Tyrrell and Peckham, 1976). There can be no justification now for giving prophylactic irradiation to the supradiaphragmatic nodes because the disease tends to metastasise to the lung parenchyma and extensive high-dose irradiation will compromise bone marrow tolerance for any future cytotoxic therapy. With such a variation in disease patterns, histology and staging, and with the low incidence plus high potential for curability, there is an obvious need for national cooperation and trials in the management of these tumours.

It has been estimated from lymphadenectomy specimens that the incidence of occult metastases in the para-aortic nodes in seminoma is between 10 and 19% (Castro and Gonzalez, 1971), and there is no doubt that post-operative irradiation in early stage seminoma has increased survival significantly. However, these figures are based on early work and do not include correlation to lymphographic results so the true incidence in Stage I disease is probably quite low. In this series no patients with Stage I disease relapsed, as would be expected, and there appears to be no indication for extended field irradiation. Routine irradiation of the mediastinum and supraclavicular fossae has been advocated for Stage II disease in seminomas and is practised in some centres; this however may be unnecessary. With only lymphographic changes in the para-aortic nodes the probability of further lymph node spread is small. In this series no patients developed supradiaphragmatic node involvement and in previous series similar patients without lymphograms would have been staged as I and received treatment only to the abdomen. Results from such management have generally been excellent (Castro and Gonzalez, 1971; Doornbos et al., 1975). In this series 15% of patients relapsed in supradiaphragmatic nodes and all were controlled locally with further irradiation. All these patients had abnormalities of the IVU, as well as the lymphogram, and it would seem that prophylactic radiotherapy to the supradiaphragmatic nodes is only indicated where paraaortic disease is so advanced as to be either palpable REFERENCES or cause ureteric or renal displacement or obstruction. In the management of seminomas the IVU is probably Blandy, J. P., Hope-Stone, H. F. & Dayan, A. D. (1970). Turnouts o f the Testicle, pp. 145-165. William Heinmann the most important post-operative investigative Medical Books Ltd, London. procedure. Castro, J. R. (1972). Testicular Tumours, ed. Johnson, D. E., The results for Stage I teratoma appear to correlate pp. 181-207. Henry Kimpton Publishers, London. well with some other published data for patients Castro, J. R. & Gonzalez, M. (1971). Results in treatment of pure seminoma of the testis. American Journal o f Roenttreated by orchidectomy and abdominal irradiation genology, 111,355-359. (Oliver, 1979) but in most studies these patients were Doornbos, J. F., Hussey, D. H. & Johnson, D. E. (1975). not lymphographically staged and such series Radiotherapy for pure seminoma of the testis. Radiology, 116,401-404. undoubtedly contain a proportion of more advanced tumours thus potentially lowering the survival rates. Kuhn, C. R. & Johnson, D. E. (1972). Testicular Tumours, ed. Johnson,D. E., pp. 37-46. Henry Kirnpton Publishers, In Tyrrell and Peckham's series (1976) where patients London. were staged lymphographically there was an 88% Oliver, R. T. D. (1979)i Modern management of testicular disease-free survival at two years with only 5% teratomas. Cancer Topics, 2 (8), 6-8. relapsing in the abdomen following irradiation. In our Smithers, D., Wallaces, E. N. K. & Wallace, D. M. (1971). Radiotherapy for patients with tumours of the testicle. series there was a high incidence (24%) of relapse in British Journal o f Urology, 43, 83-92. the para-aortic nodes which suggests that a watch Tyrrell, C. J. & Peckham,M. J. (1976). The response of lymph policy is not without risk, and with a likelihood of node metastases of testicular teratoma to radiation occult metastases of this level post-operative irradiatherapy. British Journal o f Urology, 48~ 363-370.