CASE REPORT: Late Relapse in Germ Cell Testicular Cancer

By: Jaime Andrés Cajigas, MD, Marly Clinic, Bogotá, Colombia; William Quiróga Matamoros, MD, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, Colombia; Alejandro Fernández, MD, Marly Clinic, Bogotá, Colombia; Yineth Camila Tunjano, MD, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, Colombia; Mónica M. Medina, MD, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, Colombia; Dania V. Carreño Barrera, MD, Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, Colombia | Posted on: 09 Mar 2023


Figure 1. Urography, July 2020.
Figure 2. Positron emission tomography-CT, July 2020.
Figure 3. Positron emission tomography-CT, October 2020.
Figure 4. Multiparametric nuclear MRI of the prostate, July 2022.
Figure 5. Multiparametric nuclear MRI of the prostate, July 2022.

Germ cell tumors are the most common cause of cancer in men between the ages of 15 and 35. They are one of the most curable solid tumors, with a survival rate greater than 80%.1,2 However, approximately 10% of all patients will experience relapse of the disease during follow-up, the majority presenting in the first 2 years of follow-up and only 1% to 6% beyond 2 years. The approximate incidence according to the histology of the tumor is 3.2% in nonseminomatous tumors and 1.4% in seminoma.2-4 This reinforces the importance of long-term follow-up of this pathology. Additionally, in those patients with late relapse, a more aggressive biology of the tumor has been demonstrated, requiring multimodal management.2

Late relapses of testicular cancer occur beyond 2 years after initial successful treatment.2 Most patients experience this relapse during the first 5 years of follow-up, with reports in the literature of exceptional cases where relapse occurrence exceeds 10 years. This is why it is valuable to expand the knowledge about the characteristics of this type of presentation, as well as the treatment modalities used and the response.

Clinical Case

A 57-year-old male patient with a history of nonseminomatous testicular cancer diagnosed in 1989, with a histological diagnosis of teratoma + embryonal carcinoma + choriocarcinoma (involving 90% of the testicle), who was treated with orchiectomy without adjuvant chemotherapy or radiotherapy presented with late tumor relapse (31 years).

In May 2020, the patient presented with pelvic pain radiating to the lower limbs, accompanied by urinary symptoms and macroscopic hematuria with expulsion of clots. A renal and urinary tract US was performed showing a pelvic mass, and via cystoscopy it was possible to see the mass bulging through the right ureter, with biopsy revealing atypical urothelial cells suggestive of a reactive process.

CT urography found dilatation in the collecting system and proximal two-thirds of the right ureter, with decreased enhancement of the right renal parenchyma secondary to the presence of a pelvic mass with irregular and well-defined contours measuring 82×60×69 mm in diameter. This mass involved the distal third of the right ureter, as well as the ureterovesical junction, the right posterior and lateral wall of the bladder, the right lobe of the prostate gland, and the right seminal vesicle (Figure 1).

Positron emission tomography (PET)-CT elucidated a pelvic mass located in the vesicorectal space of approximately 65×90×59 mm, with peripheral uptake of 16.52 standardized uptake value of radiotracer, with malignant appearance and behavior and signs of tumor necrosis or cystic degeneration. Intense uptake of radiotracer compromised the distal portion of the right internal iliac artery and right renal cortical artery, associated to hydronephrosis, probably caused by obstruction. The right ureter was dilated and lost within the described mass in the vesicorectal space. There was no abnormal uptake in the left testicle (Figure 2).

The patient was taken to laparoscopy and biopsy, which revealed germinal nonseminomatous tumor with morphology consistent with embryonal carcinoma and endodermal sinus tumor. He started treatment with bleomycin, etoposide, and cisplatin, and after 3 cycles, PET-CT revealed rectovesical space mass with significant metabolic intensity decrease (74% in relation to a partial metabolic response). No enlarged lymph nodes or hypermetabolic adenopathies were identified (Figure 3).

The patient had an excellent response to treatment both from the clinical and biomarker point of view, with initial α-fetoprotein (AFP) of 217 and post-treatment AFP of 7.3. Therefore, he was scheduled to undergo urological surgery for resection of residual mass and ureter reanastomosis.

After 2 years of follow-up of the previous treatment for testicular cancer relapse, the patient presented with an elevated PSA of 13 ng/mL with a normal digital rectal examination and pre-biopsy prostate MRI with PI-RADS (Prostate Imaging-Reporting Data System) 4 lesions, for which he underwent prostate fusion biopsy on August 23, 2022 with the discovery of grade group 3 prostate adenocarcinoma, with unfavorable NCCN (National Comprehensive Cancer Network) intermediate-risk disease staging (Figures 4 and 5). PET-prostate-specific membrane antigen was negative for metastatic lesions, so treatment with curative intent was performed with radical prostatectomy and standard lymphadenectomy on October 19, 2022 with final disease staging pT3aN0M0R0 grade group 3 with 65% Gleason 4 and present cribriform glands. Currently PSA is undetectable.


This is a rare and challenging case of a very late relapse of nonseminomatous germ cell tumor-embryonal carcinoma and endodermal sinus tumor 31 years after orchiectomy, which also had an atypical clinical presentation of a mass in the pelvic region with involvement of the ureter’s distal third suggesting a urothelial origin.

Only a few cases of relapses occurring 20 years after the initial presentation are reported in the literature. For example, Ansari and Hajigholami,5 and Arafat et al4 described patients with nonseminomatous germ cell tumors with very late relapse at 27 years after the initial presentation. These cases emphasize the importance of lifelong surveillance of patients with germ cell tumors, even patients with extremely low risk for late relapse, including those with clinical stage I disease.

In order to anticipate the appearance of these late relapses, there are widely documented risk factors for the development of metastatic disease in patients with stage I testicular cancer, such as lymphovascular invasion and the percentage of embryonal carcinoma in nonseminomatous tumors.2,3 Some biomarkers are currently being studied to predict relapses, finding utility in proteins such as MIB-1, CXCL12, β-catenin, and possibly CXCR4; however, their validation is lacking in larger, multicenter, well-defined studies.3

Screening is usually carried out during routine follow-up examinations, either by elevated serum markers such as AFP or human chorionic gonadotropin, radiographic findings, or clinical symptoms6 such as low back pain or a palpable abdominal mass. It should be noted that early detection will have an impact on prognosis, since symptoms in the initial presentation have been associated with lower cancer-specific survival and overall survival.2

Regarding the histology of late relapse, it is known that it is usually biologically more aggressive than that found during retroperitoneal lymphadenectomy for primary tumors. Teratoma is usually found in approximately 20% to 30% of positive node specimens at primary lymphadenectomy and in 40% of patients with post-chemotherapy lymphadenectomy.2

Given the high rate of chemoresistance in late relapsed tumors, the cornerstone of treatment is complete surgical excision, although salvage chemotherapy regimens have been described, such as platinum, ifosfamide, paclitaxel, etoposide, and epirubicin, although with low complete response rates,7 at 20.7% for late response and 42.1% for early relapse. Therefore, the aim of follow-up beyond 5 years shifts to the detection of late side effects of treatment.8

Just as platinum-based chemotherapy has increased cancer-specific and overall cancer-free survival, it has also been associated with secondary neoplasms.9 Studies have shown an increased risk of second malignancies among testicular cancer survivors (TCS),10 especially after radiation therapy (RT) and chemotherapy, with an increased relative risk of approximately 1.4-fold of developing subsequent prostate cancer, among other second cancer types.10 Zhang et al presented a cohort of 282 TCS, with data extracted from the SEER (Surveillance, Epidemiology, and End Results) database controlling for age at the time of diagnosis and era of diagnosis of prostate cancer.11 The standardized risk ratio analysis showed no statistically significant increased risk for grade of the disease among TCS who had received prior RT (radiotherapy) compared with TCS with no prior RT. The latency between the 2 diagnoses ranged from 12 to 443 months, with a median of 211 months. In our case, 33 years elapsed, almost twice as long as described in the literature. However, it is known that testicular cancer survivors with subsequent diagnosis of prostate cancer are more likely to be detected at a younger age than those men with primary prostate cancer (with a median age of 69, P < .001), with detection rates of 65.2% vs 37.6% for age ≤65, and 34.8% vs 62.4% for age >65 (P < .001).11 Although the exact reason for this observation is not clear, this difference may be multifactorial, including cancer susceptibility at a younger age in TCS and/or the result of earlier detection under routine cancer surveillance as part of survivorship care after testicular cancer treatments.

A prospective historical cohort by Hellesnes et al of 5,625 TCS shows an increased risk of solid neoplasia after 2 or more cycles of platinum-based chemotherapy when compared to surgery as single management of up to 72%.9 Both the L-field technique and paraaortic RT were associated with 1.6-fold increased risks for second cancer in comparison to surgery only. On the other hand, follow-up studies imply radiation exposure in constant CT scans, with an association of increased risk of second cancer.12,13

In view of these data, it is debatable if regular follow-up of all testicular cancer patients beyond 5 years is a good use of medical resources as well as keeping health professionals alert about the risk of secondary solid neoplasms in this population, emphasizing careful evaluations to ensure a timely diagnosis.

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