Testicular Cancer

7. FOLLOW UP AFTER CURATIVE THERAPY

7.1. Minimal recommendations for follow-up

Based on different risks of relapse depending on diagnosis and initial treatment, three major follow-up groups can be defined:

1. patients with seminoma stage I;
2. patients with non-seminoma stage I on AS;
3. all patients having received either adjuvant treatment or curative chemotherapy for good- and intermediate-prognosis metastatic disease (according to the IGCCCG) achieving a complete remission with, or without, surgery (for seminoma this includes residual lesions < 3 cm, or residual lesions > 3 cm that are FDG-PET-negative).

It is important to note that patients not achieving a complete remission or presenting with poor-prognosis disease should be followed up individually by specialised centres. Tables 8-10 show the minimal recommendations for follow-up of the three different groups based on recommendations developed at a European Society for Medical Oncology (ESMO) consensus conference [268].

Both MRI and CT can be used to evaluate the retroperitoneum, pelvis and inguinal regions for sites of metastatic disease from GCT [269,270]. Magnetic resonance imaging benefits from an absence of ionising radiation but is more time consuming and less readily available than CT [271]. Given the frequency of follow-up, over a number of years some studies have estimated a risk of up to 1 in 300 of second malignancy related to CT imaging follow-up alone [272], although more recent dose saving protocols and limitations on field of view will have mitigated this somewhat. Nevertheless, this risk could be excluded by the use of MRI for follow-up.

Both MRI and CT rely predominantly on size cut-offs for evaluation given the excellent spatial resolution of both modalities, with morphological assessment for features such as necrosis and irregular shape an adjunct. Sensitivity and specificity vary according to the size cut-off used [269]. However, studies have shown comparable excellent results between MRI and CT with up to 98% sensitivity on MRI for the detection of retroperitoneal nodal metastases in GCT [273]. It has, however, been demonstrated that reader experience is important when interpreting images [274]. In the setting of GCT, one study demonstrated decreased sensitivity for detection of retroperitoneal nodal disease on MRI when reported by a trainee radiologist with sensitivity of detection of 80% [272]. However, experienced radiologists in the same study achieved sensitivity for detection of nodal disease of 97% with good interobserver agreement. It was therefore suggested that if MRI is to be used instead of CT for follow-up this be done in centres/units with oncological radiologists who routinely report MRI and CT in patients with GCT, rather than general radiologists who may only occasionally see such imaging. Consequently, MRI of the abdomen can be used as an alternative to CECT in experienced centres [275].

The diagnostic accuracy of FDG-PET-CT is best described and therefore recommended in seminoma patients with post-chemotherapy residual masses > 3 cm in largest diameter as outlined in section 6.3.2.1. This should be performed at least two months after completion of chemotherapy as earlier scans may be misleading due to inflammation. The changes are related to tumour necrosis. The use of FDG-PET-CT is not currently recommended during surveillance. Retrospective analyses have indicated a high diagnostic accuracy for staging and follow-up in patients with CS 1 during surveillance or for determining the stage in more advanced disease [276]. However, to minimise radiation exposure and considering the supporting data for the use of MRI [270], the panel currently do not recommend the use of FDG-PET-CT during surveillance.

Serum tumour markers are the least invasive and most accessible follow-up investigations. The established serum tumour markers, such as AFP, β-hCG, and LDH, may yield false positive results, so their levels should be correlated with imaging findings or repeated in serial measurements [277]. Serum tumour markers can detect microscopic disease that is not yet visible on cross-sectional imaging in a small proportion of patients, and therefore, they should be measured at the recommended prescribed intervals [278].

MiR-371a-3p has a high diagnostic accuracy for detecting all histologies of GCT except teratoma and has potential to detect disease recurrence earlier than AFP, β-hCG, LDH, or cross-sectional imaging [279]. However, before this promising test can be recommended in routine practice, a validated assay and cut-off definitions in prospective cohorts are required to mitigate the risk of false positive findings, unnecessary restaging, anxiety, or over-treatment.

Regarding the use of US examination of the contralateral testis, the majority of the consensus meeting participants did not support repeat US investigation, either with negative biopsy or if no contralateral biopsy has been performed [268].

A very late relapse (VLR) after five years is a rare event occurring in approximately 0.5% of patients based on a population-based analysis [257]. The aim of follow-up beyond five years therefore shifts to detection of late side effects of treatment and imaging tests are not routinely recommended.

Most patients with VLR are diagnosed due to symptoms, although in up to 50% elevated tumour markers are present in NSGCTs [257,280]. Patient education regarding relapse symptoms and clinician awareness are important elements of survivorship management. Early use of imaging and tumour markers with suspicion of relapse is encouraged.

Table 8: Recommended minimal follow-up for seminoma clinical stage I on active surveillance or after adjuvant treatment (carboplatin or radiotherapy)

Table 9: Recommended minimal follow-up for non-seminoma clinical stage I on active surveillance

* In case of high-risk (LVI+) a minority of the consensus group members recommended six times.
** In case of high-risk (LVI+) a majority of the consensus group members recommended an additional CT at eighteen months.
*** Recommended by 50% of the consensus group members.
LVI+ = Lymphovascular invasion present.

Table 10: Recommended minimal follow-up after adjuvant treatment or complete remission for advanced disease (excluded: poor-prognosis and no remission)

* In conjunction with abdominopelvic MRI/CT in case of pulmonary metastases at diagnosis.
** In case of teratoma in resected residual disease: the patient should remain with the uro-oncologist.

7.2. Quality of life and long-term toxicities after cure of testicular cancer

The vast majority of patients will be cured with five-year relative survival rates of approximately 95% in Western Europe. Testicular cancer patients are usually between 18-40 years of age at diagnosis and life expectancy after cure extends over several decades [281]. Patients should be informed before treatment of common long-term toxicities, which are avoided or minimised by adherence to international guidelines.

During follow-up, patients should be screened and treated for known risk factors such as hypertension, hyperlipidaemia, and testosterone deficiency. Adverse health outcomes (AHOs) are more commonly found in TC patients who received chemotherapy than those cured by surgery alone. Further, modifiable risk factors do contribute to AHOs like hypertension and noise exposure to hearing impairment or smoking to Raynaud phenomenon [282]. Therefore, a healthy lifestyle should be promoted during the follow-up consultations. Adverse health outcomes are associated with unemployment, which is found clearly increased in TC survivors (TCSs) as compared to a male normative population [283]. When follow-up by the TC clinician is terminated, a written cancer survivorship plan addressing late toxic effects, lifestyle recommendations, recurrence risk, and cancer-specific follow-up may be helpful [200,284].

*For more information regarding long term toxicities and QoL issues, please see appendix 5, available online https://uroweb.org/guidelines/testicular-cancer/publications-appendices