Radiocirugía como alternativa terapéutica en la recaída tardía de un tumor testicular no seminomatoso. Reporte de caso

Stereotactic radiosurgery as a therapeutic alternative for late relapse of nonseminomatous germ cell tumor: A case report

Resumen

Introducción. La recaída tardía de tumores testiculares de células germinales no seminomatosos (TTCGNS) es una entidad poco frecuente. Su tratamiento estándar involucra cirugía y quimioterapia; sin embargo, en algunos casos en los que la enfermedad es irresecable, hay toxicidad acumulada o el paciente se niega a recibir tratamientos invasivos, la radioterapia se considera una alternativa terapéutica.

Presentación del caso. Hombre de 54 años con antecedente de TCGNS en estadio IIA tratado con orquiectomía radical y 2 ciclos de BEP (bleomicina, etopósido, cisplatino) con adecuado control de su enfermedad, en quien 25 años después de este tratamiento se identificaron dos lesiones retroperitoneales y aumento en los niveles de alfa feto proteína (AFP). Se inició quimioterapia de rescate con EP (cisplatino, etopósido), pero esta tuvo que suspenderse por toxicidad cardiovascular, por lo cual se optó por radiocirugía con dosis de 45Gy en 6 fracciones, obteniéndose una respuesta favorable con control negativo de los marcadores tumorales (AFP, HCG y LDH) y reducción del tamaño de una de las lesiones.

Conclusiones. Este caso resalta la necesidad de establecer protocolos de seguimiento rigurosos y personalizados a largo plazo en pacientes con TTCGNS debido al riesgo de recaídas tardías, incluso décadas después del tratamiento inicial. La radiocirugía se presenta como una opción terapéutica efectiva en estos escenarios.

Abstract

Introduction: Late relapse of nonseminomatous germ cell tumors (NSGCT) is a rare entity. Standard treatment involves surgery and chemotherapy; however, in some cases in which the disease is unresectable, accumulated toxicity occurs or the patient refuses to receive invasive treatments, so radiotherapy is considered as a therapeutic alternative.

Case presentation: A 54-year-old man with a history of stage IIA NSGCT treated with radical orchiectomy and 2 cycles of BEP (bleomycin, etoposide, cisplatinum) with adequate control of the disease, presented with two retroperitoneal lesions and increased levels of alpha-fetoprotein (AFP) 25 years after this treatment. Rescue chemotherapy with EP (etoposide, cisplatin) was started, but it had to be suspended due to cardiovascular toxicity. Consequently, radiosurgery was decided upon with a dose of 45Gy in 6 fractions, obtaining a favorable response with negative control of tumor markers (AFP, hCG, and LDH) and a reduction in the size of one of the lesions.

Conclusions: This case emphasizes the need to establish rigorous and personalized long-term follow-up protocols in patients with NSGCT due to the risk of late relapses, even decades after initial treatment. Radiosurgery is considered an effective therapeutic option in these scenarios.

https://doi.org/10.15446/cr.v11.120492

Keywords: Radiotherapy; Germ Cell Tumor; Relapse; Treatment

Palabras clave: Radioterapia; Tumor De Células Germinales;
Recaída; Tratamiento

Valeria del Pilar Goyeneche-Medina

Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Urology Specialty -
Bogotá D.C. - Colombia

Rodolfo Varela-Ramírez

Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Urology Specialty -
Bogotá D.C. - Colombia

Instituto Nacional de Cancerología -
Urologic Oncology Unit -
Bogotá D.C. - Colombia

Corresponding author

Valeria del Pilar Goyeneche-Medina. Especialidad en Urología, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá D.C. Colombia
Correo electrónico: valeriagoyenechemd@gmail.com.

Received: 20/06/2025 Accepted: 30/11/2025

Presentación del caso. Hombre de 54 años con antecedente de TTCGNS en estadio IIA
tratado con orquiectomía radical y 2 ciclos de BEP (bleomicina, etopósido, cisplatino) con adecuado control de su enfermedad, en quien 25 años después de este tratamiento se identificaron dos lesiones retroperitoneales y aumento en los niveles de alfa feto proteína (AFP). Se inició quimioterapia de rescate con EP (cisplatino, etopósido), pero esta tuvo que suspenderse por toxicidad cardiovascular, por lo cual se optó por radiocirugía con dosis de 45Gy en 6 fracciones, obteniéndose una respuesta favorable con control negativo de los marcadores tumorales (AFP, HCG y LDH) y reducción del tamaño de una de las lesiones.

IntroducTIOn

Late relapse of testicular nonseminomatous germ cell tumors (NSGCT) refers to disease recurrence more than 2 years after initial treatment (1). This type of relapse is rare, with an incidence of 2-3% (1), making it difficult to diagnose and follow up. It can be identified when alpha-fetoprotein (AFP) levels are elevated (1), with the retroperitoneum being the most common site of presentation (1,2), followed by the lung, mediastinum, neck, supraclavicular region, and pelvis (2). Very late recurrence, i.e., after 5 years after the initial presentation, is a rare event that occurs in approximately 1% of patients with testicular germ cell tumors (TGCT) and is associated with a poor prognosis (2).

Patients with late relapse NSCGT have unique clinical features that require a different approach to treatment compared to patients who relapse less than
2 years after initial therapy (1). While no optimal treatment has been established, it involves surgery, chemotherapy and, in some cases, radiotherapy depending on the extent of the disease and the patient’s response to previous treatments (1,3).

Surgery remains the treatment of choice for patients with late relapse of NSCGT as it increases the likelihood of cure, especially in patients with isolated retroperitoneal lymph node disease who undergo complete resection of residual disease (2). When the disease is advanced, cisplatin-based chemotherapy is the standard of care (4).

Radiotherapy is not typically used to treat NSCGTs because these neoplasms are relatively radioresistant (5,6); however, it is considered an additional therapeutic option in patients with unresectable lesions, tumors refractory to chemotherapy, and cumulative toxicity from previous treatments (5). It has also been established that, contrary to what has been traditionally described in the literature, teratomas are not completely radioresistant, so stereotactic ablative radiotherapy may be an option for local control of the disease (5).

The following is the case of a patient with a late relapse of NSCGTs, in whom two persistent residual retroperitoneal masses were identified and treated by stereotactic radiosurgery, achieving good outcomes.

Case presentation

In 1998, a 54-year-old man presented to the emergency department of a tertiary care institution in Bogotá D.C., Colombia, complaining of pain and an increase in the average volume of the left testicle. The patient had no relevant medical history, and physical examination revealed an enlarged and hardened left testicle, with no signs of local inflammation. Given the findings, an ultrasound scan was requested, revealing a solid intratesticular mass. Laboratory tests also revealed positive tumor markers for AFP. Based on these results, he was diagnosed with a testicular tumor and underwent a left orchiectomy that same year. Histopathological examination confirmed mixed stage IIA NSCGT.

The patient underwent adjuvant chemotherapy with two cycles of BEP (bleomycin, etoposide, and cisplatin) administered as follows: bleomycin 30 000 IU intravenously on days 1, 8, and 15; cisplatin 20 mg/m² intravenously as a continuous infusion on days 1 to 5; etoposide 100 mg/m² intravenously as an infusion on days 1 to 5; and pegfilgrastim 6 mg subcutaneously on day 6. Each cycle was administered at 21-day intervals on an outpatient basis.

One year later, despite testing negative for tumor markers (lactate dehydrogenase, AFP, and beta-hCG), routine checkups revealed two persistent residual retroperitoneal masses, leading to a bilateral retroperitoneal lymphadenectomy, with the pathology report confirming the presence of a teratoma.

The patient continued to be followed up at the same institution, maintaining negative tumor markers until August 2023, when an increase in AFP levels was detected. In view of the findings, a computed axial tomography (CT) scan was performed one month later, showing two lesions: a 4 cm lesion located in the para-aortic region, posterior to the left renal vein, and another 1 cm lesion located posterior to the left common iliac artery (Figure 1).

Figure 1. Computed tomography of the abdomen showing a mass in the para-aortic region, posterior to the left renal vein (arrow).

Source: Image obtained while conducting the study.

In October 2023, an 18F-FDG positron emission tomography was performed, showing that both lesions had peripheral uptake and that the para-aortic lesion was 2 cm larger than in the previous CT scan (Figure 2). Considering the findings, salvage chemotherapy was initiated with 2 cycles of EP (etoposide and cisplatin) administered as follows: cisplatin 80 mg/m² intravenously on day 1 and etoposide 100 mg/m² intravenously on days 1 to 3, with cycles every 21 days. During treatment, the patient began to experience episodes of dyspnea on slight exertion, for which an electrocardiogram was performed, indicating second-degree atrioventricular block. This finding was confirmed by a Holter study performed in January 2024, which also documented frequent ventricular extrasystoles. This made it possible to determine the presence of cardiovascular toxicity associated with the chemotherapy regimen, so it was suspended.

Figure 2. 18F-FDG positron emission tomography showing peripheral uptake of the para-aortic mass (arrow).

Source: Image obtained while conducting the study.

In February 2024, due to the new findings, the case was presented at a multidisciplinary board (oncologic urology, clinical oncology, radiation oncology, radiology, nuclear medicine), which decided to proceed with stereotactic body radiation therapy (SBRT) with a target planning volume established based on positron emission tomography, adding a margin of 4 mm for each lesion. The established regimen consisted of a total dose of 45 Gy (Gray) administered in 6 fractions of 7.5 Gy each, with a frequency of 3 sessions per week. The target volume covered the adenopathy plus the established oncologic margin. This treatment was completed in April 2024 (Figure 3). In the follow-up visit that took place in June 2024, tumor markers were found to be negative.

Figure 3. Dose distribution of stereotactic body radiation therapy treatment planning. The pink area indicates the planning target for the lesions.

Source: Image obtained while conducting the study.

One year later, tumor markers remained negative and a CT scan established that the retroperitoneal para-aortic lesion had shrunk in size to 4 cm, showing cystic characteristics and no contrast medium uptake, while the lesion adjacent to the left common iliac artery maintained its size, presented calcifications, and did not show contrast medium uptake. No adverse effects associated with radiotherapy were identified.

At the time of writing this case report, the patient was still under permanent follow-up (every three months during the first year after treatment and every six months after the second year).

Discussion

The treatment of NSCGTs includes radical orchiectomy followed by cisplatin-based chemotherapy and, in some cases, retroperitoneal lymphadenectomy if there are residual lesions (1). When patients experience late relapses, treatment must be multidisciplinary and individualized, since therapeutic options may be limited due to the cumulative toxicity of previous treatments (1).

Surgery is essential for the management of late relapses in patients with NSCGTs, but in cases of unresectable multifocal disease, dose-intensive chemotherapy and consolidation surgery must be considered (3). This approach offers better outcomes when treatments targeting residual disease are administered without resorting to therapeutic options that may pose additional serious side effects (3).

Radiotherapy has traditionally had a limited role in the treatment of NSCGTs because they are considered to be radioresistant; however, given that advances in radiotherapy have allowed for greater precision in its administration, as well as increased dose and decreased treatment-related morbidity, it could now be considered a good option for the management of these tumors (6). In the present case, radiosurgery (SBRT) was used to treat two retroperitoneal masses due to cumulative toxicity from previous chemotherapy, particularly cardiovascular toxicity associated with cisplatin (7).

Radiotherapy, specifically radiosurgery, has the advantage of accurately irradiating tumor lesions, minimizing damage to surrounding tissues (6,8). In our case, radiotherapy with 45 Gy administered in 6 fractions (7.5 Gy each) significantly reduced the size of one of the lesions, which became cystic, and made the other lesion maintain its size. Furthermore, with this regimen, none of the masses showed contrast uptake and the tumor marker tests were negative, indicating a good control of the disease.

The effectiveness of radiotherapy in the treatment of late relapse of NSCGTs has only been documented in case reports. For example, Gulia et al. (9) described the case of a patient with a late relapse of NSCGT, in whom a high-precision ablative dose of radiation was administered to the recurrent para-aortic lymph node mass using SBRT, achieving long-term disease control (>6 years). For their part, Kita et al. (10) reported the case of a patient with a late relapse of NSCGT treated with intensity-modulated radiotherapy, who achieved complete tumor marker response and remained in complete clinical remission for 3 years; this approach represents a treatment option that allows more precise irradiation, thereby reducing the risk of damage to surrounding healthy tissues and optimizing disease control. Likewise, Satyanarayan et al. (5) presented the case of a patient with NSCGT who developed multiple pulmonary metastases and refused surgery, so he received a total dose of 54 Gy administered in 3 fractions with adequate tolerance and no reported toxicity, achieving complete serologic and radiographic remission a decade after the initial treatment. Finally, Laflamme et al. (11) published the case of a patient with mediastinal NSCGT, who presented viable tumor in the excised tissue after a cycle of chemotherapy and resection surgery, which required additional chemotherapy; however, since he declined this treatment, SBRT (50 Gy in 5 fractions) was chosen, obtaining adequate results with negativation of tumor markers at one month, significant reduction of the residual mass at 6 months, and remission of the disease 3 years after treatment, which suggests that SBRT can be an effective option for the treatment of NSCGTs in cases refractory to chemotherapy (11).

As mentioned above, NSCGTs have traditionally been believed to be radioresistant (6,12), although, this seems not to be entirely true since epigenetic mechanisms have been found to be related to cisplatin resistance, such as the presence of low OCT3/4 levels and elevated cytoplasmic p21 levels (12). Moreover, the hypomethylation of OCT3/4 observed in NSCGT subtypes emphasizes the interplay of several epigenetic mechanisms, suggesting the need for a more comprehensive approach to address chemoresistance (12). This hypomethylation following radiation exposure could potentially reverse cisplatin resistance in a manner similar to other hypomethylating agents (such as 5-azacitidine), which have been shown to help restore cisplatin sensitivity in this scenario (6). Assessing OCT3/4 and p21 levels in patients with NSCGT could help to identify platinum-resistant patients and, thus, opt for stereotactic ablative radiotherapy (SABR) as an alternative therapy. Similarly, it has been established that radiotherapy causes changes in DNA methylation, which occur in parallel with classical biological responses to radiation, suggesting a possible relationship between radiation resistance and epigenetics, specifically DNA methylation (13).

The present case highlights the need for long-term follow-up through imaging studies and tumor markers for patients with testicular cancer, because there is a risk of late relapses that can manifest years or even decades after treatment despite the fact that initial treatment may be successful (14), as in our patient, in whom the relapse was detected more than 20 years after initial treatment.

Conclusions

Late relapses of NSCGTs can occur even decades after initial treatment, so patients with this condition require prolonged oncologic follow-up. Radiosurgery is considered a crucial treatment option, as it offers a non-invasive and high-precision modality for controlling lesions locally. However, it has some limitations as it does not address systemic disease, for which salvage chemotherapy is reserved.

Ethical considerations

To prepare this case report, informed consent was obtained from the patient, who consented to the use and publication of his clinical data and photographs. Anonymity of the information was preserved throughout the document.

Conflicts of interest

None stated by the authors.

Funding

None stated by the authors.

Acknowledgments

To the patient, for consenting to the publication of this report, since the information shared will contribute to expand knowledge in this area and will promote improved care and treatment of the aforementioned conditions in the future.

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