10
ClinicalRadiology (1993) 47, 149 158 Review Staging of Testicular Germ Cell Tumours D. MacVICAR Department of Radiology, Royal Marsden Hospital, Sutton, Surrey Testicular germ cell tumours occupy a place of particular importance in modern oncology. They afflict young men, often at the peak of their social and economic responsibi- lities. The incidence has been rising throughout this century and almost doubled between the periods 1964-68 and 1979-82, such that figures from 1981 indicated that in England and Wales, one white male in 500 could expect to develop testicular cancer [ 1,2]. The highest incidence rates are in white men in the USA, Scandinavia, UK and Western Europe, while low rates are found in Asians, Africans, Puerto Ricans and North American Blacks, in whom there is no incidence peak in young men [3,4]. However, these tumours are highly sensitive to chemo- therapy and radiotherapy, and provide a model of a curable neoplasm. Even with metastatic disease, the prognosis is good and cure rates of over 90% can be expected with early stage disease [5]. Clinical manage- ment is optimized by a multidisciplinary approach in which radiological staging is an integral part and the radiologist's involvement may be unusually rewarding. HISTOLOGICAL CLASSIFICATION Ninety-five per cent of testicular tumours are germ cell tumours (GCT), 4% are lymphoma and 1% are rarities such as Sertoli cell tumours, interstitial (Leydig) cell tumours and paratesticular embryonal sarcomas. Of 876 patients with primary testicular GCT presenting to the Royal Marsden Hospital between 1980 and 1988, 40% had pure seminoma, the remainder had non-seminoma- tous germ cell tumours (NSGCT) of various histological types [1]. Histological classification has prognostic impli- cations and two systems are in current use. Table 1 shows the British Testicular Tumour Panel classification [6] alongside the World Health Organization classification [7], which forms the basis of the American system of nomenclature. The juxtaposed terms are almost synony- mous, although the British system has the advantage (to the radiologist) of simplicity. STAGING SYSTEMS system developed synchronously with the evolution of body CT scanning and its principal advantage is that it gives a clear indication of sites of disease and tumour bulk. The Medical Research Council Working Party on Testicular Tumours reviewed 458 patients treated at six British centres between 1976 and 1982. Using the Royal Marsden Hospital staging classification, the contribution of various factors to survival was assessed using the Cox regression method. Factors shown to be associated with worse survival rates are para-aortic nodes greater than 5 cm diameter (Stage IIC disease); more than three lung metastases, one of which was greater than 2 cm diameter (Stage IV L3); and liver or bone disease (Stage IV H + or IV Bo +) [10]. Gross elevation of serum tum our markers also portends poor survival, as does age if over 30 years at presentation. Havifig established that tumour bulk and site are important prognostic indicators, the Royal Marsden Hospital classification provides a reproducible and precise system which relies heavily on radiological investigation. The Indiana University system (Table 3) is widely used in the USA and describes disease as minimal, moderate or advanced, subdividing into numerical stages on the basis of clinical parameters such as palpability and resectabi- lity. Other American institutions such as the MD Anderson Cancer Centre and Memorial Sloan Kettering Cancer Centre use local systems. It has been shown that the variety of criteria used results in marked differences in allocation of patients into good and poor risk categories for treatment trials [11]. The situation in the American literature may be confusing to the non-specialist, but the staging criteria, which are frequently predominantly clinical, should be specified [ 12,13]. There is little doubt that staging has become more accurate since the introduction of CT scanning. The ability of CT to detect retroperitoneal and mediastinal masses has led to more frequent diagnosis of advanced stage disease, and attention has been drawn to the phenomenon of 'stage migration', due to improved imaging, as a source of misleading statistics for survival in cancer [14,15]. It seems appropriate to use a staging system based on current technology, and in this article only the Royal Marsden Hospital system will be dis- cussed. Staging classifications of testicular GCT likewise suffer from a lack of international uniformity. This is unfortu- nate since disease prognosis and choice of therapy are influenced by disease stage, and prospective comparison of treatment schedules depends on reliable and consistent classification. In the UK, use of the Royal Marsden Hospital classification (Table 2) [8] is almost universal and it has been adopted by the European Organization for Research and Treatment of Cancer (EORTC) [9]. This Correspondence to: Dr D. MacVicar, Department of Radiology, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT. SEMINOMA vs NSGCT Within the Royal Marsden Hospital system, identical staging criteria are used for all GCTs. Investigation protocols are influenced by the biological behaviour of the diseases. Seminoma afflicts older patients, and spreads in a more predictable way, initially to the retroperitoneal nodes, then to the mediastinum and subsequently to the lungs and other viscera. NSGCT spreads in a more haphazard way, and the lungs are

Staging of testicular germ cell tumours

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Page 1: Staging of testicular germ cell tumours

Clinical Radiology (1993) 47, 149 158

Review

Staging of Testicular Germ Cell Tumours D. MacVICAR Department of Radiology, Royal Marsden Hospital, Sutton, Surrey

Testicular germ cell tumours occupy a place of particular importance in modern oncology. They afflict young men, often at the peak of their social and economic responsibi- lities. The incidence has been rising throughout this century and almost doubled between the periods 1964-68 and 1979-82, such that figures from 1981 indicated that in England and Wales, one white male in 500 could expect to develop testicular cancer [ 1,2]. The highest incidence rates are in white men in the USA, Scandinavia, UK and Western Europe, while low rates are found in Asians,

�9 Africans, Puerto Ricans and North American Blacks, in whom there is no incidence peak in young men [3,4]. However, these tumours are highly sensitive to chemo- therapy and radiotherapy, and provide a model of a curable neoplasm. Even with metastatic disease, the prognosis is good and cure rates of over 90% can be expected with early stage disease [5]. Clinical manage- ment is optimized by a multidisciplinary approach in which radiological staging is an integral part and the radiologist's involvement may be unusually rewarding.

HISTOLOGICAL CLASSIFICATION

Ninety-five per cent of testicular tumours are germ cell tumours (GCT), 4% are lymphoma and 1% are rarities such as Sertoli cell tumours, interstitial (Leydig) cell tumours and paratesticular embryonal sarcomas. Of 876 patients with primary testicular GCT presenting to the Royal Marsden Hospital between 1980 and 1988, 40% had pure seminoma, the remainder had non-seminoma- tous germ cell tumours (NSGCT) of various histological types [1]. Histological classification has prognostic impli- cations and two systems are in current use. Table 1 shows the British Testicular Tumour Panel classification [6] alongside the World Health Organization classification [7], which forms the basis of the American system of nomenclature. The juxtaposed terms are almost synony- mous, although the British system has the advantage (to the radiologist) of simplicity.

STAGING SYSTEMS

system developed synchronously with the evolution of body CT scanning and its principal advantage is that it gives a clear indication of sites of disease and tumour bulk. The Medical Research Council Working Party on Testicular Tumours reviewed 458 patients treated at six British centres between 1976 and 1982. Using the Royal Marsden Hospital staging classification, the contribution of various factors to survival was assessed using the Cox regression method. Factors shown to be associated with worse survival rates are para-aortic nodes greater than 5 cm diameter (Stage IIC disease); more than three lung metastases, one of which was greater than 2 cm diameter (Stage IV L3); and liver or bone disease (Stage IV H + or IV Bo + ) [10]. Gross elevation of serum tum our markers also portends poor survival, as does age if over 30 years at presentation. Havifig established that tumour bulk and site are important prognostic indicators, the Royal Marsden Hospital classification provides a reproducible and precise system which relies heavily on radiological investigation.

The Indiana University system (Table 3) is widely used in the USA and describes disease as minimal, moderate or advanced, subdividing into numerical stages on the basis of clinical parameters such as palpability and resectabi- lity. Other American institutions such as the MD Anderson Cancer Centre and Memorial Sloan Kettering Cancer Centre use local systems. It has been shown that the variety of criteria used results in marked differences in allocation of patients into good and poor risk categories for treatment trials [11]. The situation in the American literature may be confusing to the non-specialist, but the staging criteria, which are frequently predominantly clinical, should be specified [ 12,13].

There is little doubt that staging has become more accurate since the introduction of CT scanning. The ability of CT to detect retroperitoneal and mediastinal masses has led to more frequent diagnosis of advanced stage disease, and attention has been drawn to the phenomenon of 'stage migration', due to improved imaging, as a source of misleading statistics for survival in cancer [14,15]. It seems appropriate to use a staging system based on current technology, and in this article only the Royal Marsden Hospital system will be dis- cussed.

Staging classifications of testicular GCT likewise suffer from a lack of international uniformity. This is unfortu- nate since disease prognosis and choice of therapy are influenced by disease stage, and prospective comparison of treatment schedules depends on reliable and consistent classification. In the UK, use of the Royal Marsden Hospital classification (Table 2) [8] is almost universal and it has been adopted by the European Organization for Research and Treatment of Cancer (EORTC) [9]. This

Correspondence to: Dr D. MacVicar, Department of Radiology, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT.

SEMINOMA vs NSGCT

Within the Royal Marsden Hospital system, identical staging criteria are used for all GCTs. Investigation protocols are influenced by the biological behaviour of the diseases. Seminoma afflicts older patients, and spreads in a more predictable way, initially to the retroperitoneal nodes, then to the mediastinum and subsequently to the lungs and other viscera. NSGCT spreads in a more haphazard way, and the lungs are

Page 2: Staging of testicular germ cell tumours

150 CLINICAL RADIOLOGY

Table 1 - Histological classifications

British Testicular Tumours Panel World Health Organization (Pugh and Cameron 1976) (Mostofi and Sobin 1977)

Table 3 - The Indiana University classification system

Stage Definitions

Seminoma Teratoma differentiated (TD)

Malignant teratoma intermediate (MTI)

Malignant teratoma undifferentiated (MTU) Malignant teratoma trophoblastic (MTT)

Yolk sac tumour

Seminoma Teratoma

Mature Immature

Teratoma with malignant transformation, embryonal carcinoma and teratoma

Embryonal carcinoma Polyembryoma Choriocarcinoma with or

without embryonal carcinoma and/or teratoma

Yolk sac tumour

f requent ly involved at p resen ta t ion and m a y be the first site o f metastases .

Seminoma is exquisi tely sensit ive to rad io the rapy . A low dose (c. 20 Gy) to the pa ra - ao r t i c and ipsi la teral pelvic nodes is giveq in mos t centres in the absence o f a re t roper i tonea l mass. The low toxici ty o f this regime justifies the use o f ' p rophy lac t i c ' r ad io the r apy to t rea t potent ia l micrometas tases . Af te r a b d o m i n a l rad io- therapy, the init ial site o f metas tases m a y be the medias t i - num, which is not rout ine ly t reated. The appa ren t skip lesion is expla ined by the presence o f unsuspected media- st inal micrometas tases at the t ime o f init ial t rea tment .

T u m o u r marke r s m a y be present in bo th seminoma and N S G C T . A l p h a feto p ro te in (~FP) is e levated in 47-65% o f pat ients with N S G C T and f l -human chor ionic gonado- t roph in ( H C G ) is e levated in 31-60%. A t least one m a r k e r is present in 56-84% of pa t ien ts [16-19]. In marker -pos i t ive N S G C T , any sus ta ined elevat ion o f levels should prec ip i ta te a rad io log ica l search for sites o f relapse. Seminoma results in a ra ised H C G in 7 -15%, while 0tFP is raised in 0 - 4 % [17-19]. Rad io log ica l investi- ga t ion is therefore the sole means o f ear ly detec t ion o f

Minimal disease 1 2

3

4

Moderate disease 5

6

Advanced disease 7

Elevated HCG and/or AFP only Cervical nodes (_+ non-palpable

retroperitoneal nodes) Unresectable, but non-palpable,

retroperitoneal disease Minimal pulmonary metastases - less than

five per lung field and the largest < 2 cm (_ non-palpable abdominal disease)

Palpable (/> 10 cm) abdominal mass as only disease

Moderate pulmonary metastases - five to ten pulmonary metastases per lung field and the largest < 3 cm or a mediastinal mass < 50% of the intrathoracic diameter or a solitary pulmonary metastasis > 2 cm ( + non-palpable abdominal disease)

Advanced pulmonary metastases - mediastinal mass > 50% of the intrathoracic diameter or greater than ten pulmonary metastases per lung field or multiple pulmonary metastases, largest > 3 cm (+ non-palpable abdominal disease)

Palpable abdominal mass plus pulmonary metastases 8.1 - minimal pulmonary 8.2 - moderate pulmonary 8.3 - advanced pulmonary

Hepatic, osseous or CNS metastases

recurrence in the ma jo r i ty o f pat ients with seminoma. The search for new ma rke r s for tes t icular t umours has y ie lded a bewi lder ing a r r ay o f candida tes , o f which p lacen ta l a lkal ine phospha t a se and p lacenta l and p regnancy re la ted pro te ins have been mos t t ho rough ly invest igated [17,20-22]. However , none have been shown to a d d more useful i n fo rma t ion to that p rov ided by H C G and ~FP es t imat ions .

Table 2 - The Royal Marsden Hospital staging classification for testicular germ cell tumours

Stage Definitions

I IM

II

III

IV

M N O ABC

Lung L1 L2 L3 H+ Br+ Bo+

No evidence of metastases Rising serum markers with no other evidence of

metastases Abdominal node metastases < 2 cm in diameter 2 5 cm in diameter > 5 cm in diameter Supradiaphragmatic node metastases Mediastinal Supraclavicular/cervical/axillary No abdominal node metastases Node size defined as in Stage II Extralymphatic metastases

~< 3 Metastases > 3 Metastases all < 2 em in diahaeter > 3 Metastases, one or more > 2 cm in diameter Liver metastases Brain metastases Bone metastases

R A D I O L O G I C A L S T A G I N G T E C H N I Q U E S

Whi le C T scanning has become the mos t i m p o r t a n t inves t igat ion in s taging o f tes t icular tumours , p la in chest r a d i o g r a p h y and u l t r a sound f requent ly m a k e significant cont r ibu t ions . L y m p h o g r a p h y , which used to p lay a key role, is now used only in selected pat ients . The p lace o f magnet ic resonance imaging ( M R I ) is not yet es tabl ished, bu t it is emerging as a useful tool in cancer r ad io logy and in cer ta in s i tua t ions m a y prov ide unique in format ion .

C T S c a n n i n g

Effective use o f CT scanning relies on ass iduous technique, a knowledge o f the lympha t ic a n a t o m y and pa t te rns o f t u m o u r spread, and famil iar i ty with a n u m b e r o f d iagnos t ic pitfalls. The rad io logis t is of ten called on to m a k e crucial decis ions on whether re t roper i tonea l noda l disease is present . In N S G C T Stage II disease is t rea ted with systemic chemothe rapy , while Stage I disease m a y be adequa te ly t rea ted by o rch idec tomy alone. A p p r o x i -

Page 3: Staging of testicular germ cell tumours

STAGING OF TESTICULAR GERM CELL TUMOURS 151

Echelor d e

(a )

RIGHT LEFT

Aortocaval nodes

Precaval nodes

Paracaval nodes

Echelon . ~ , ~ ' node--W

Pre aortic nodes

Para aortic nodes

, _ Echelon node

Retrocaval node , , ,

" f " - . : - . " . , . : .']i",

~:.. . ~. . ] �9 -....: . . . . ,, , ,

(b)

Fig. l - (a) Schematic representation of lymphatic drainage of the testes. 'Echelon' nodes are not opacified by foot lymphography. (b) Retroperi- toneal nodal groups at the level of L2.

mutely 25-30% of Stage I patients relapse on surveillance and effective 'rescue' chemotherapy is available [23-30]. The remainder are thus spared any further treatment, although prolonged follow-up is necessary. While the

attenuation characteristics and shape of suspect lesions in the retroperitoneum may assist the radiologist, the distinction between Stage I and Stage II disease is made fundamentally on size criteria. The chief shortcoming of CT is its inability to detect microscopic tumour deposits in normal-sized nodes. Until relatively recently, retroperi- toneal lymph node dissection was widely practiced as a staging and therapeutic procedure. Histologically-corre- lated data shows that 20-30% of patients considered Stage I harbour occult metastases which are not detected by any imaging method [31-33].

False negative results are therefore inevitable, but the numbers must be minimized by elimination of observer error and recognition of the limitations of the technique used. The effect of size criteria on the diagnostic accuracy of CT has been addressed in two recent histologically- correlated studies [34,35]. Lien et al. reviewed the abdo- minal CT scans of 90 patients who went forward to surgery. At their institution only patients with lymph node masses greater than 2 cm diameter received chemo- therapy, all other patients proceeding to retroperitoneal lymph node dissection following radiological staging. Histological examination revealed metastases in 38 patients. Applying an upper limit of normal of 15 mm for nodes resulted in a sensitivity of 37%, with 24 false negatives out of 38 patients. However, there was only one false positive, giving a specificity of 98% and overall accuracy of 72%. Using t0 mm as the upper limit of normal, sensitivity was 47%, specificity 87%, overall accuracy 70%; using 5 mm, sensitivity was 71%, speci- ficity 67%, accuracy 69%. If all visible nodes were deemed abnormal, sensitivity rose to 100% but the specificity was unacceptably low at 10%. The results of Stomper et al. were similar, and earlier studies using nodal diameters of 10-15 mm as the sole criterion for metastatic disease report false negative rates of 29-44% [12,13,33]. The choice of an upper limit of normal is somewhat arbitrary and depends to some extent on the attitude of the radiologist and clinical colleagues towards the relative acceptability of false negative and false positive results. At the Royal Marsden Hospital, a retroperitoneal node over l0 mm (maximum transverse diameter) is deemed metastatic, while a node less than 8 mm is deemed normal. Between 8 mm and l0 mm is considered suspicious. The size problem is compounded by the fact that normal nodes become larger the further caudal they are [36-38]. Fortunately, the patient's prognosis is unlikely to be affected by a delay of a few days or weeks while further clarification is sought. The view of Stomper et al. seems reasonable that, in the presence of an equivocal node, confirmatory evidence of involvement is needed. Tumour marker estimation is the least invasive means of confirma- tion, but rescanning after an interval, lymphography or needle biopsy may be necessary.

The site of a suspected nodal metastasis may also sway radiological diagnosis. Detailed descriptions of the lym- phatic drainage of the testis are available in the seminal anatomical work of Rouvi6re [39]. Four to eight lym- phatic vessels emerge from the testis and follow the vessels and spermatic cord through the internal ring, subse- quently crossing the ureter and spreading out in arches to lymph nodes around the aorta and IVC throughout the upper and lower lumbar regions (Fig. 1). The most lateral of these, the 'echelon' nodes, lie along the psoas muscle between L1 and L4. For practical purposes, nodes to the left of a sagittal plane drawn through the centre of the

Page 4: Staging of testicular germ cell tumours

152 CLINICAL RADIOLOGY

Fig. 2 Metastasis from left sided seminoma to the left para-aortic nodal group. Nodal diameter is less than 2 crn. No other lesion was present, thus the disease was Stag~ IIa.

(a)

Fig. 3 - Teratoma of right testis. The low attenuation of the nodal metastasis in the inter-aorticocaval group is typical. Max imum diameter of the node was 2 cm, and disease was Stage IIb.

(b)

Fig. 4 - (a) Suspicious mass-like area of soft tissue at tenuation in left para-aortic region (arrow). (b) Scan 2 cm caudal shows a retro-aortic left renal vein (arrow). The ' tadpole' shape is sufficiently frequent and familiar that intravenous contrast is not always necessary for confirma- tion.

aorta can be considered left sided (i.e. pre-aortic and left para-aortic nodes). Paracaval, retrocaval and inter-aorti- cocaval nodes are therefore right sided. Direct testicular lymphography has shown that on the left the primary drainage site is at the level of L2, just below the renal vessels, while the right testis drains to nodes between L1 and L3 [40]. Lymphographic crossover from right to left is relatively common, but left to right crossover is rare. This is reflected in surgical [41] and CT studies [42,43]. Dixon et aL [42] studied 55 patients with CT-detected retroperi- toneal nodal metastases. In patients with left sided testicular primaries, nodal enlargement was confined to the left para-aortic region in 93 % and was predominantly left sided in the remaining 7%. In patients with right sided testicular tumours, nodal enlargement was confined to

right sided nodal groups in 68% and was predominantly right sided in 86%. Fourteen per cent of cases showed adenopathy which was equal bilaterally, confirming the relative frequency of crossover from right sided lesions. However, the diagnosis of contralateral nodal involve- ment in the absence of spread to ipsilateral nodes should be treated with scepticism. The initial site of metastasis from left sided tumours is classically nodes just below the renal vessels, while metastases from right sided tumours show a wider distribution through upper and lower lumbar nodes [41].

Attention to the shape and attenuation of retroperito- neal structures helps in avoiding errors in staging. Metastases from seminoma are typically soft tissue density, while NSGCT may be low attenuation or cystic

Page 5: Staging of testicular germ cell tumours

STAGING OF TESTICULAR GERM CELL TUMOURS 153

(a) (a)

(b)

Fig. 5 - (a) Soft tissue density in left para-aortic region in patient with left sided testicular tumour (arrow). (b) Contrast-enhanced scan shows a left ascending lumbar communicant vein. The ascending lumbar veins usually run anterior to the medial end of the lumbar transverse processes (open arrow) before joining the lowest subcostal veins to form the hemiazygos vein on the left and the azygos vein on the right. In many patients a branch ascends medial to the psoas muscle (small arrow) to join the left renal vein, forming a varicosity (curved arrow) in 9% of patients, which may simulate a nodal mass.

[44,45] (Figs 2, 3). Neither will enhance with iodine containing contrast media to the same degree as vessels. Vascular anomalies are a potential source of false positive diagnoses. Large gonadal veins, duplication of the IVC, left sided IVC, retroaortic or circumaortic renal vein, and left ascending lumbar communicant veins are common [46,47], but there is usually a clue such as the tadpole shape of a r etroaortic renal vein, or the presence of a tubular structure on sequential scans (Figs 4,5). Dynamic contrast enhancement will usually be decisive in diagnosis and is mandatory in equivocal cases although routine use of contrast is not necessary. Lymphatic vessels measuring up to 6 mm may also be visible as low attenuation

(b)

(c) Fig. 6 (a) A chest X-ray shows an apparently solitary nodule (arrow). (b,c) CT scan shows the nodule in the left lung. However, there are smaller nodules not visible on the plain radiograph (arrows).

Page 6: Staging of testicular germ cell tumours

154 CLINICAL RADIOLOGY

Fig. 7 - Seminoma. Bilateral adrenal metastases. (a)

structures in the retrc~peritoneum [48]. A bowel loop may mimic a nodal mass but on turning the patient prone its position and shape will change.

Thoracic CT should be included in the initial staging scan for all germ cell tumours. It is the most sensitive method available for detection of nodal metastases in the mediastinum and peripheral pulmonary deposits [49-53]. Lung nodules as small as 3 mm diameter are easily detected with modem CT scanners (Fig. 6). When multiple nodules are present, a false positive diagnosis of meta- static disease is unlikely, but if a single lesion is seen, it may be necessary to confirm the diagnosis with repeat scanning 4-6 weeks later to demonstrate enlargement of the nodule.

Scan technique in the chest is optimized by using contiguous slices of up to 10 ram. In the abdomen a gap between scans is permissible. Lien et al. [54] compared contiguous 10 mm thick slices with a non-contiguous scanning technique which was simulated by reading alternate slices only in a group of patients prior to retroperitoneal lymph node dissection. Their group of 100 patients included those previously included in a study on the effect of size criteria on sensitivity of tumour detection. A non-contiguous technique with gaps of 10 m m led to a drop in sensitivity from 71% to 66% when 5 m m was used as the upper limit of normal node size; from 47% to 39% for the 10 mm criterion; and from 37% to 26% for the 15 mm criterion. Specificity, and positive and negative predictive values were only slightly influenced. Other authors have reported that non-contiguous scan- ning is nearly as accurate as contiguous for a variety of tumours, including lymphomas and testicular neoplasms [55], and some standard textbooks recommend 10 mm thick CT slices with I0 m m gaps for the retroperi toneum [56]. However, to set 8 m m as the upper limit of normal for node size and then allow 10 m m gaps is inconsistent. A degree of compromise seems appropriate, and a slice thickness of 8-10 mm at 12-14 m m intervals would certainly be acceptable.

Continuation of the scan through the pelvis results in considerable gain in diagnostic information at little additional cost. Involvement of iliac and inguinal nodes is

(b)

Fig. 8 (a) Seminoma. A nodal metastasis was suspected in the inter- aorticocaval group (arrow). (b) Lymphography confirms a metastasis. There is a filling defect and contrast is seen in the normal nodal tissue compressed at the periphery of the gland.

not uncommon, particularly on the right, reaching 28% in one series [41]. It is frequently associated with para-aortic node enlargement but may occur in isolation. A history of maldescent and orchidopexy, congenital anomalies of the urinary tract or breach of the tunica vaginalis by tumour or surgery increases the likelihood of ilio-inguinal in- volvement, but in some patients no predisposing factors are present [57].

Cranial CT is not part of routine staging, but is a sensitive method of detecting cerebral metastases in the presence of neurological symptoms. Asymptomatic brain metastases may be seen at presentation in patients with aggressive disseminated disease and are more common in patients with trophoblastic teratoma than any other histological type. Bony disease may be observed, and careful scrutiny of the entire body on CT may be rewarding as a wide variety of uncommon sites of metastasis from germ cell tumours have been described,

Page 7: Staging of testicular germ cell tumours

STAGING OF TESTICULAR GERM CELL TUMOURS 155

including kidney, adrenals, inferior vena cava, muscle, spleen, seminal vesicles, prostate and pericardium [58] (Fig. 7).

Lymphography

The major limitations of lymphography which have led to its replacement by CT are that it is unpleasant for the patient, may be technically difficult to perform, gives no information on extralymphatic viscera and it only reliably opacities nodes up to the level of the first or second

�9 lumbar vertebra. False negative rates of 10-42% are reported, not dissimilar to abdominal CT [33,59-61]. False negatives occur because some nodes fail to opacify. The 'echelon' nodes (Fig. 1) and the right upper lumbar nodes may not be demonstrated by foot injections. Deposits of tumour typically appear as filling defects, compressing the opacified normal lymphoid tissue into a thin rim at the periphery of the gland (Fig. 8). As the metastasis grows, it breaks through the capsule and may obliterate the node completely. Once the capsule has been breached, disease bulk cannot be assessed accurately. However, lymphography has the capability to detect deposits in normal size lymph nodes. Some authors have recommended that lymphography should be performed in the presence of a normal CT scan in NSGCT and as the initial investigation in seminoma [62]. The concept that subsequent lymphography would improve the false nega- tive rate of CT staging in patients with a normal CT scan is attractive. However, experience has been disappoint- ing, with two studies showing that true positive lympho- grams occur at a rate of one in seven patients with false negative CT scans [61,63], and that false positive lympho- grams occur at a similar rate. The argument that lympho- graphic contrast may be used in follow-up to detect recurrence is not valid, as one study has shown that lymphographic follow-up enabled detection of recurrence in only 13% of cases, compared with 76% for CT scanning and 68% for tumour markers. In no patient was lymphography the only positive test at the time of recurrence [64]. Authors from a number of centres in the UK and Europe have recommended abandonment of lymphography as a routine staging procedure for NSGCT [63-66] although there are few data published for seminoma. It remains useful for assessment of equivocal nodes in marker negative disease where repeat CT scan is not acceptable.

Chest Radiographs

Although not as sensitive as CT [50,51] plain chest radiography is mandatory at the time of initial staging. Pulmonary nodules, pleural masses or effusions, and mediastinal nodal masses may be apparent and a normal study forms a baseline for follow-up. Chest radiographs can be obtained more frequently than thoracic CT, and appearance of a lung nodule or displacement of a mediastinal line may be the first evidence of relapse. There is no longer any indication for conventional whole lung tomography [53].

Ultrasound

Although techniques continue to improve ultrasound evaluation of the retroperitoneum remains difficult owing

to limitations imposed by adipose tissue and overlying bowel gas. Failure to visualize the retroperitoneum adequately in patients with testicular tumours ranges from 8-17% [13,67]. Although some authors report comparable accuracy of ultrasound and CT in the retroperitoneum [68], ultrasound has not become a standard staging investigation. It may be used where CT is not readily available and is frequently of clinical utility as an adjunct to CT staging. In thin patients with little retroperitoneal fat, ultrasound may be easier to interpret than CT; a node involved by a testicular tumour appears as an echo-poor mass and NSGCT may contain cystic areas [69]. Ultrasound is an appropriate way to clarify equivocal lesions on hepatic CT.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) can demonstrate enlarged lymph nodes and its multiplanar imaging capa- bility is useful in demonstrating the relationships of nodal masses to vessels. Hopes that information derived from T 1- and T2-weighted images would enable discrimination of benign from malignant causes of nodal enlargement have not been fulfilled. To date there is little information on the accuracy of MRI in detection of retroperitoneal disease, although one early report demonstrated no benefit in using MRI rather than CT [70]. Like lympho- graphy and ultrasound, MRI is limited as a staging technique by its inadequacy above the diaphragm.

Imaging of the Primary Tumour

Imaging has a limited role in detection of testicular tumours. Clinical examination remains of paramount importance in diagnosis although ultrasound is valuable in patients who are difficult to examine clinically and in patients who present with metastases in whom an occult testicular primary is suspected [71]. Neither ultrasound nor MRI is accurate in local staging of the primary tumour [72] and this is best left to the pathologist. Ultrasound of the contralateral testis is frequently per- formed in view of the small but significant incidence of bilateral tumours.

SURVEILLANCE OF STAGE I DISEASE

Surveillance policy is now accepted management of Stage I NSGCT, but is less well established for seminoma. At specified intervals, the patient undergoes what is essentially a complete clinical and radiological restaging. The frequency of these intervals depends to some extent on the facilities available, but there is considerable support for the view that surveillance should only be carried out at specialized centres [26].

Surveillance of Non-seminomatous Germ-Cell Tumours

In countries such as the UK, where follow-up is relatively easy, the policy of surveillance has been shown to be safe and spares 70% of patients further treatment following orchidectomy [23-30]. Radiological follow-up should include chest radiograph, and thoracic and abdo- minopelvic CT scanning. In the Medical Research Coun- cil (MRC) retrospective review of surveillance policies [23], the intensity of surveillance varied between centres,

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especially in the use of CT scans. Centres were divided into three groups: those using, on average, 3-5 CT scans per year; those using 1-2 scans per years; and those using 0-1 scans per year. There was no significant tendency for those centres doing scans more frequently to detect relapses at a less advanced stage and 83% of relapses were detected by clinical examination, elevated tumour markers and chest radiographs. A prospective MRC trial was inaugurated in 1984 which will compare a variety of scanning schedules. Data from this trial has indicated that 80% of recurrences occur in the first 12 months of surveillance, and few patients relapse later than 2 years [73]. Although late recurrences are seen, it is unlikely that routine CT scanning after 2 years will alter overall survival rates. Certain histological features can be identi- fied in the primary tumour (vascular and lymphatic invasion, presence of undifferentiated tumour and absence of yolk sac elements) which are associated with higher rates of early relapse [23]. For these patients more intensive surveillance or adjuvant chemotherapy may be indicated, but for the present no clear consensus exists on the optimum frequency of follow-up CT scans.

Surveillance of Seminoma

Only a limited number of centres have explored surveillance policies for Stage I seminoma. The conven- tional treatment is to give adjuvant irradiation to the retroperitoneal nodes. This policy is highly successful in preventing recurrence and relatively non-toxic owing to the low dose required. Recent studies report a relapse rate of under 2% [74,75]. Follow-up CT is not indicated and plain chest radiography will suffice for these patients. Surveillance for Stage I disease following orchidectomy alone resulted in a 13% relapse rate in a series of 113 patients [76]. In all of the 15 relapses, the retroperitoneal nodes were involved and in one a solitary pulmonary nodule was found. Regular abdominal CT scanning is required for surveillance. The relatively slow natural history of seminoma means that surveillance may be less intensive than for NSGCT, but must be prolonged and in the absence of a sensitive serum tumour marker, is dependent on radiological investigation. The Royal Marsden Hospital surveillance study involved yearly CT scanning for 5 years [76]. It is not yet clear whether surveillance policies are appropriate for Stage I semi- noma, but the concept of 'cos t effectiveness' will certainly enter the debate.

CONCLUSION

The recent spectacular improvements in the prognosis of testicular germ cell tumours make it imperative that the most appropriate treatment is selected for each patient. Disease stage is a very important factor in treatment decisions. The Royal Marsden Hospital staging system is recommended for use in the UK, as it provides compre- hensive information on disease site and bulk. In addition, its use will enable accurate staging of patients entering multicentre comparative trials of new, lower toxicity treatment regimens. Whole body CT and chest radiogra- phy are the central and essential investigations, and subsidiary techniques such as MRI, ultrasound and lymphography may be of benefit in individual patients.

Acknowledgements. The author is grateful to the Cancer Research Campaign and Daniel Marks Fund for continuing financial support of the work of the department. Thanks are also due to Dr Janet Husband for help and advice during preparation of the article; Pippa Johnston and Pauline Kennedy for secretarial help; Pippa Johnston for the art work on Fig. 1; Janet MacDonald and Jackie Seckle for preparation of the illustrations; Dr Colin Meanock and the Editor of Clinical Radiology for permission to use the illustrations in Fig. 5.

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