Between 2000 and 2020, 249 patients met eligibility criteria for the analysis, including 184 patients with stage 1 and 77 patients with advanced testicular seminoma (inclusive of 12 individuals who underwent FDG-PET/CT for stage 1 and advanced seminoma) (see Figure 1). Baseline clinical and demographic data is displayed in Table 1. Almost two thirds (63%) of patients in the stage 1 cohort received adjuvant radiation therapy (n = 82, 45%) or chemotherapy (n = 33, 18%) following orchidectomy. Of the patients in the advanced stage cohort who had relapsed stage 1 disease, prior adjuvant chemotherapy or radiation therapy was received by 38%.

Follow-up continued for a median of 6.4 years (range 0–17) from diagnosis for patients in the stage 1 cohort, and 27 (15%) recurrences occurred. The median time from diagnosis to FDG-PET/CT was 1.7 months (range 0-121), the median number of FDG-PET/CT performed at diagnosis or during active surveillance was 1 (range 1–3).

In contrast, patients in the advanced cohort were followed for a median of 7.7 years (range 0–25) from original diagnosis (with initial stage 1 or de novo advanced disease), and 28 (36%) episodes of relapsed/refractory disease were observed (including 12 individuals or 16%, initially evaluated in the stage 1 cohort). The median time from diagnosis to first FDG-PET/CT was 9.1 months (range 0-166) and the median number of FDG-PET/CT performed for evaluation of advanced seminoma was 2 (range 1–7).

In patients with stage 1 seminoma, 197 FDG-PET/CT were performed, however three FDG-PET/CT had no available follow-up data and were excluded from further analyses. Of the remaining 194 FDG-PET/CT, 115 (60%) were performed at baseline and the remaining 79 (41%) were performed during active surveillance. The most common indication for FDG-PET/CT was as a ‘routine’ component of clinical practice during diagnostic workup (n = 80, 41%) or active surveillance (n = 41, 21%) (see Figure 2).

Evaluable FDG-PET/CT performed for clinical stage 1 seminoma. (PPV = positive predictive value, NPV = negative predictive value, FDG-PET/CT = 2-18fluoro-deoxy-D-glucose positron emission tomography with computerised tomography)

Of the 115 baseline FDG-PET/CT, all were negative, and 93 had ≥ 24 months of follow-up during which time, four recurrences occurred (in four patients). The NPV for FDG-PET/CT predicting non-recurrence at 24 months was 95.7% (see Table 2 and Supplementary Table 1). Of 78 FDG-PET/CT ordered during active surveillance with available follow-up, 18 (23%) were reported as positive with recurrence confirmed in all cases following apparent radiologic response after definitive treatment (PPV 100%). Of the 45 active surveillance FDG-PET/CT reported as negative with ≥ 24 months of follow-up, four episodes of recurrence occurred in four patients (NPV 91.1%). The median time-to-recurrence following negative FDG-PET/CT was 1.6 years (range 1–4).

When indicated by clinical suspicion during active surveillance (n = 37), inclusive of abnormal radiology (n = 32), elevated serum tumour markers (n = 4) and symptoms (n = 1), 17 FDG-PET/CT were reported as “positive” for recurrent seminoma. All were true positives (PPV 100%) evidenced by radiologic response to definitive treatment. Of those with ≥ 24 months follow-up in this cohort, the NPV was 85.7% (two recurrences amongst 14 patients). In real terms, the use of FDG-PET/CT in patients with stage 1 seminoma in this setting correctly identified 12/37 patients who did not have recurrence (12/14 FDG-PET/CT reported as negative), and correspondingly, may prevent unnecessary treatment in ~ 1/3 individuals undergoing FDG-PET/CT for this indication.

In patients with advanced seminoma, 154 FDG-PET/CT were performed, however nine FDG-PET/CT had no available follow-up data and were excluded from all further analyses. Of the remaining 145 FDG-PET/CT, 25 (17%) occurred at baseline. 70 (48%) were performed following chemotherapy or radiation therapy (to evaluate response), 50 (34%) were performed in follow-up after prior curative treatment of advanced seminoma. The most common indication for FDG-PET/CT was investigation of abnormal radiology at baseline or during follow-up (n = 49, 32%), or immediately following chemotherapy to assess response (n = 44, 29%) (see Figure 3).

Evaluable FDG-PET/CT performed for advanced seminoma. (PPV = positive predictive value, NPV = negative predictive value, FDG-PET/CT = 2-18fluoro-deoxy-D-glucose positron emission tomography with computerised tomography)

Overall, 24/25 baseline scans were reported as positive (96%), and active disease was confirmed in all cases (PPV 100%). Of these, two (8%) were confirmed on histology, with the remainder confirmed on follow-up radiology after treatment. One baseline FDG-PET/CT performed for investigation of abnormal radiology was reported as negative; however, this individual received definitive radiation therapy and sustained a complete response, and the finding was considered a false negative (see Table 2).

When FDG-PET/CT was ordered following chemotherapy or radiation therapy to evaluate response, 10 (14%) were reported as positive and residual active disease was confirmed in six cases corresponding to a PPV of 60.0%. Of the 46 FDG-PET/CT reported as negative with ≥ 24 months of follow-up, five episodes of recurrence occurred in five patients (NPV 89.1%). The presence and size of any residual mass triggering FDG-PET/CT was not available. The median time-to-recurrence following the negative FDG-PET/CT was 11 months (range 6–20). As such, of the 71 FDG-PET/CT performed following definitive treatment, 41 (58%) correctly identified no residual seminoma and avoided unnecessary treatment.

In an evaluation of 50 FDG-PET/CT performed during follow-up of prior curative treatment of advanced testicular seminoma (inclusive of FDG-PET/CT ordered routinely and for clinical suspicion of recurrent disease), one patient had an equivocal FDG-PET/CT result leaving 49 FDG-PET/CT in this analysis. Of these, 24 (49%) were reported as positive and recurrence was confirmed in 20 cases following additional definitive treatment (PPV 83%). Of the 20 FDG-PET/CT reported as negative with ≥ 24 months of follow-up, one episode of disease recurrence occurred, corresponding to a NPV of 95%. Notably, this patient experienced intracranial relapse detected on magnetic resonance imaging three weeks following FDG-PET/CT.

When indicated by clinical suspicion alone (n = 36), inclusive of abnormal radiology (n = 25), elevated serum tumour markers (n = 5) and symptoms (n = 7) during follow-up, PPV was 100% while NPV was 93.8% in those with ≥ 24 months follow up (1 recurrence amongst 16 patients). Practically, the use of FDG-PET/CT in patients with advanced seminoma who had clinical suspicion of recurrence following definitive treatment, correctly identified 15 patients who did not experience recurrence and correspondingly, prevented unnecessary treatment being given to 45% of patients.

Of the 90 FDG-PET/CT reported as consistent with active seminoma, SUVmax was available for 19 (86%) in the stage 1 cohort, and 34 (50%) in the advanced disease cohort. There was no difference in mean SUVmax between stage 1 and advanced cohorts (9.33 versus 8.52, p = 0.65). When analysed together by recurrence status (true positive versus false positive), higher SUVmax was more frequently seen in patients with seminoma than no active malignancy (9.56 versus 5.10, p = 0.14), however this did not meet statistical significance. Utilising aggregated SUVmax data, the PPV of SUVmax when greater than the 1st interquartile range (IQR) (SUVmax>4.7, n = 34), median (SUVmax>6, n = 25) and 3rd IQR (SUVmax>11.9, n = 12) was 91%, 96% and 100%, demonstrating higher predictive value associated with higher SUVmax cut-offs.