Patient characteristics

In most of the patients in the MSKCC [7] and Indiana University [6,17] series, the pathological diagnosis of the initial tumor was nonseminoma-tous GCT (Table 1). However, these data should be interpreted with caution because of the bias inherent in series from major specialized centers, which include many patients with advanced disease who either failed first-line chemotherapy or had unresectable tumors at diagnosis and were referred for further treatment. The findings of Dieckmann and colleagues [18] in an unselected group of patients with late relapse may represent the actual incidence more accurately. These authors reported that of 122 patients from 24 institutions in Germany with a diagnosis of late-relapse GCT, 50 (41%) had had a primary pure testicular seminoma. Gerl and colleagues [9] found a similar risk for late relapse in patients with nonseminom-atous and seminomatous GCT.

The time to relapse according to several large studies ranges widely, from 2 to 32 years, with a median of 7 to 10 years [6,7,17]. Although many years may pass before a person becomes symptomatic, the time to relapse beyond the third year is unpredictable, often leading patients and physicians to stop follow-up after this point. Accordingly, studies report that 60% to 72% of late relapses are detected by the presence of symptoms, and only 28% to 40% by elevated markers or abnormal radiographic studies [7,17]. In the series presented by Dieckmann and colleagues [18], patients were diagnosed earlier, at a median interval of 4 years to late relapse, and more cases (61%) were detected during routine follow-up. The proportion of patients presenting with symptoms appeared to be directly associated with the length of follow-up.

The most common site of late relapse is the retroperitoneum (47% to 83% of patients), followed by the lungs and mediastinum. Accordingly, the most common symptoms are back and abdominal pain. Several studies found that in 48% to 65% of patients who later developed late recurrences, the initial tumor was limited to the retroperitoneum [6,7,17]. Less common sites of relapse are the cervical nodes, liver, bone, and brain [5-7,9,10,17-19]. In 57% of patients, the disease is limited to one anatomical site [17].

Most patients with late relapse of nonsemi-nomatous GCT have elevated levels of tumor markers. AFP is the predominant marker in this subgroup (76% to 52% of patients), followed by HCG (28% to 10% of patients) [5-7,9,17,18]. In some cases (10% of patients with nonseminoma-tous GCT), HCG is the only elevated marker at late relapse [18]. The increase in AFP may precede the radiologic detection of late relapse by 2 to 44

Table i

Patient characteristics at late relapse

Table i

Patient characteristics at late relapse


Baniel et al 1995 [6]

George et al 2003 [i7]

Gerl et al i997 [9]

Ronnen et al 2005 [7]

No. of patients





Time to relapse, y,

n (%)


34 (42)

23 (2S)

ii (44)

6 (2i)


47 (5S)

60 (72)

i4 (56)

23 (79)

Pure seminoma

2 (2)

3 (4)

i (4)



79 (9S)

S0 (96)

24 (96)

29 (i00)

Elevated markers

54/76 (71)

55/S2 (67)

i7/24 (7i)


Recurrence pathology,

N (%)


66 (Si)

66/S0 (S3)

22 (SS)



15 (i9)

i4/S0 (i7)

3 (i2)


Tumor site, n (%)


43 (53)

39 (47)

i2 (4S)

24 (S3)


i9 (23)

2i (25)


ii (3S)


i0 (i2)


S (32)

S (2S)

months [5,9,17], reflecting the slow-growing nature of some of the tumors. The predominance of AFP as a marker of late relapse in nonsemi-nomatous GCT might be explained by the finding at Indiana University that yolk-sac tumor was the most common germ-cell subtype in the patients with recurrences [17].

Late-relapsing seminomatous GCT has somewhat different characteristics. Dieckmann and colleagues [18] found that 80% of the late-recurring seminomas in their series developed in patients with a first stage I tumor. The estimated risk of recurrence was 0.6% for patients after adjuvant radiotherapy for stage I seminomatous GCT [20,21], and 1.9% for patients on surveillance programs [12,13,16]. Late relapse after radiation therapy for stage I seminomatous GCT tends to occur outside the radiation field [20,21]. LDH is the predominant marker at late relapse in this subgroup (52%), followed by HCG (33%) and AFP (9%) [18].

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