Comparison of the clinical and laboratory outcomes of patients with stage I germ cell tumors undergoing adjuvant treatment and active surveillance

Aim: Testicular cancer is a rare disease that constitutes less than 1% of all male tumors and is responsible for approximately 5% of urological tumors. Germ cell tumors (GCT) account for over 95% of these cancers. Advances in the treatment of this patient group over the past 40 years have led to dramatic improvements in disease-free survival. However, there is still a need for new treatments for high-risk patients. The treatment-related toxicities in many patients who show long-term survival are more pronounced compared to other solid tumors. Striking a balance between effective treatment and long-term toxicity risk is important (1). In clinical stage I seminoma, the most important risk factors for recurrence are tumor size and invasion of the rete testis stroma. If both factors are absent, the risk of recurrence is low (6%). For non-seminomatous stage I, lymphovascular invasion (LVI) of the primary tumor is the most reliable predictor of occult metastatic disease. The percentage of embryonal carcinoma within a tumor can increase the positive and negative predictive values of LVI, but a specific prognostic threshold has not been definitively established. The presence of LVI increases the five-year recurrence risk up to 50%, whereas its absence decreases it to 15% (2). The aim of this study is to compare the clinical and laboratory outcomes of patient groups with Stage I GCT who received adjuvant therapy and those who underwent active surveillance. Material and Method: Between 2010 and 2022, data pertaining to patients who underwent radical orchiectomy with a preliminary diagnosis of testicular tumor were retrospectively compiled from the Department of Urology at Ondokuz Mayıs University Faculty of Medicine. The patients' preoperative demographic characteristics, surgical data, clinical and laboratory findings before and after surgery, as well as histopathological findings reported after surgery, were reviewed. The oncological outcomes of patients diagnosed with Clinical Stage I testicular germ cell tumors (GCT) who underwent adjuvant therapy or active surveillance were compared, and follow-up results were assessed based on clinical, radiological, and pathological features. Demographic characteristics of the patients, clinical and laboratory findings, radiological imaging (CT, MRI, FDG-PET, ultrasound), comorbidities, intraoperative features, and postoperative follow-up information were accessed using our hospital's data system and e-nabız (personal health records) data. Data regarding the patients' current status were obtained by calling patients for follow-up visits, examining hospital records and e-nabız system, or reaching out to patients via telephone. Results: A total of 129 patients with a diagnosis of Clinical Stage I GCT (Germ Cell Tumor) who underwent radical orchiectomy and had at least 6 months of follow-up were included in the study out of the 302 cases. The median age of patients in the seminoma and NSGHT groups was 33 and 25 years, respectively. The median pathological tumor size for the seminoma and NSGHT groups was 22.5 cm³ and 19.15 cm³, respectively. The median follow-up duration was 26 months for the seminoma group and 36 months for the NSGHT group. In the Stage I seminoma group, there were a total of 81 patients. Among the cases, 49 (60%) were on the right side, 30 (37%) were on the left side, and 2 (3%) were bilateral. These patients were monitored using different treatment methods, including CHT, RT and AS. The distribution of patients within subgroups was as follows: 9 patients (11%) in the CHT subgroup, 13 patients (16%) in the RT subgroup, and 59 patients (73%) in the AS subgroup. The median ages for the CHT, RT, and AS subgroups were 33, 29, and 35 years, respectively. The respective median follow-up durations were 48, 40, and 24 months. Radiological tumor volumes were calculated with median values of 12.54 cm³, 35.83 cm³, and 14.26 cm³. Similarly, pathological tumor volumes were calculated as 44.1 cm³, 27.65 cm³, and 15 cm³. The p-values for these assessments were calculated as 0.09, 0.74, and 0.46, respectively, indicating no statistically significant differences. In 1 case (11.1%) where chemotherapy was administered, a relapse occurred, while in the subgroups receiving radiation therapy (RT) and active surveillance (AS), the number of patients experiencing relapse was 0 and 7 (11.8%), respectively. Statistical analyses conducted with this data did not reveal a significant difference (p=0.42). In the univariate logistic regression analysis conducted for the risk factors in Stage I seminomas, it was determined that among these factors, a positive LVI was associated with a 2.46-fold increase in risk compared to those with a negative LVI. Additionally, for individuals with tumor sizes greater than 4 cm, there was a 1.28-fold relative risk compared to those with smaller tumor sizes. Furthermore, individuals with testicular rete testis invasion exhibited a significantly higher relapse risk of 4.26-fold when compared to those without invasion. However, none of these findings reached statistical significance. In Stage I NSGHT, out of 48 patients, 25 (52%) had a mass on the right testis, while 23 (48%) had a mass on the left testis. Among the cases, 21 (44%) received CT, and 27 (56%) were placed under the active surveillance protocol. In the chemotherapy and AI arms, median values for age were 27 and 24 years, for follow-up duration were 36 and 36 months, for radiological tumor volume were 15.84 and 30.6 cm³, and for pathological tumor volume were 10 and 21.4 cm³, respectively. Upon comparing the two subgroups, no statistically significant differences were observed. The calculated p-values were 0.28, 0.5, and 0.26, respectively. In the chemotherapy group, 2 (9%) patients experienced relapse, while in the AI-followed group, 1 (3%) patient experienced relapse; however, this difference did not reach statistical significance (p = 0.57). In the univariate logistic regression analysis conducted for the risk factors associated with relapse in Stage I NSGTs, none of the features evaluated as potential risk factors for relapse were found to be statistically significant. The risk of developing relapse was observed to be 1.1-fold higher in individuals with a positive LVI compared to those with a negative LVI. For cases with tumor sizes greater than 4 cm, the risk was 3.17-fold higher relative to those with smaller tumor sizes. In instances where embryonal carcinoma constituted more than 50% of the tumor, the risk was 1.63-fold higher compared to cases without embryonal carcinoma. Furthermore, individuals with tunica albuginea invasion exhibited a 2-fold greater risk of relapse in comparison to those without invasion. These results indicate that there is no significant difference between different treatment methods in Stage I seminoma and NSGHT groups. Conclusion: In cases diagnosed with stage I seminoma, AS protocols can be a preferred alternative for monitoring patients to protect them from the side effects of CT and RT. It should be remembered that patients included in the active surveillance protocol require close monitoring. For stage I NSGCT, AS may be considered to minimize the morbidity and mortality associated with RPLND and to protect against the systemic side effects of CT. When choosing active surveillance for stage I NSGCT patients, it is important to emphasize the need for regular and close follow-up of these patients. Keywords: Testicular cancer, Germ cell tumors (GCT), Seminoma, Non-seminomatous germ cell tumors (NSGCT), Radical orchiectomy, Stage I seminoma treatment, Stage I NSGCT treatment