Mina M. Fam, MD, and Bradley McGregor, MD, discuss the treatment landscape of testicular cancer during Testicular Cancer Awareness Month.
Although 5-year relative survival rates remain high for patients with testicular cancer, early detection, continued advances in treatment approaches, and enhanced care for survivors are crucial to further improving outcomes for patients, according to Mina M. Fam, MD.
“Testicular cancer is a disease predominantly [seen in] adolescent and young men and [this patient population] can sometimes can be embarrassed or may delay their care,” Fam, the medical director of urologic oncology at Jersey Shore University Medical Center and the medical director of robotic surgery at Ocean University Medical Center in Brick, New Jersey, said in an interview with OncLive®. “In testicular cancer in particular, early disease diagnosis and treatment are important. Having patients be aware [of the disease], learn how to do testicular self-exams, and learn when there's a warning sign to see their doctor, is important because the earlier we get to these patients, the less treatment they may need and the better outcomes they may have.”
In honor of Testicular Cancer Awareness Month, which occurs annually in April, OncLive spoke with both Fam and Bradley McGregor, MD, about the current treatment landscape of testicular cancer, emerging therapies in the space, and avenues for future research.
McGregor is the director of clinical research at the Lank Center for Genitourinary Oncology, an institute physician, and the Marra Lochiatto Investigator at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
According to the 2026 edition of Cancer Statistics, the 5-year relative survival rate in the United States (US) for patients with testicular cancer has risen from 83% in 1975-1977 to 95% in 2015-2021.1 However, testicular cancer was the fourth-highest cause of cancer death in the US in 2023 for male patients who were 20 to 39 years old.
Although multimodal therapy advances have led to testicular cancer being a highly curable malignancy, testicular cancer survivors remain at risk for long-term health consequences and other survivorship issues.2 Testicular cancer survivors can experience endocrine dysfunction, cardiovascular disease, secondary malignancies, chemotherapy-induced neuropathy, and psychosocial challenges, all of which necessitate longer follow-up.
Approximately 5% to 10% of men who undergo orchiectomy alone develop clinical or subclinical hypogonadism during follow-up. Additionally, sexual dysfunction affects approximately 25% to 40% of patients with long-term testicular cancers.
Although approximately 71% to 82% of men successfully achieve fatherhood without the use of cryopreserved sperm, up to 16% of couples will require the use of assisted reproductive technology. Thus, it is crucial to ensure preorchiectomy sperm cryopreservation is available as a proactive measure to preserve reproduction.
“Testicular cancer is a disease of young men, and the good news is that a lot of them can [achieve] really good survival outcomes,” Fam explained. “[However], with treatment, patients can [experience] adverse effects decades later. It's important to highlight the survivorship of these patients and understand that their testicular cancer journey doesn't end with their initial treatment. We need to look at them as lifelong patients and assess for some of those issues down the road.”
To address the potential long-term risks of testicular cancer treatment, there has been interest in reduced-intensity chemotherapy, radiation-sparing approaches, and surgical interventions. However, there has been a lack of long-term follow-up for most of this research, and discussion of treatment goals, comorbidities, and other factors with patients is necessary for informed treatment decisions.
McGregor noted that although novel approaches such as immunotherapies and antibody-drug conjugates have been explored in the testicular cancer space, there has not been as much progress with these agents when compared with other cancer types. “Cisplatin-based chemotherapy is highly effective at eradicating testicular cancer, so that remains the foundation. In those rare situations when we have disease that's not responding or is relapsing, there are trials ongoing looking at novel approaches and different ways to live with the chemotherapy,” he explained.
“The biggest unmet needs are [in] the patients with refractory or recurrent disease; these are some of the most [challenging] patients to [treat] in urologic oncology,” Fam added. “The good news is that there are trials coming up that will help elucidate better ways to treat these patients. There's been an increase in awareness of survivorship [care among] [patients with] testicular cancer, but it’s still not where we need to be in terms of helping [them down] the road.”
McGregor noted that he is especially excited to see data from the phase 3 TIGER study (NCT02375204), which is comparing overall survival (OS) outcomes with standard-dose combination chemotherapy comprising paclitaxel, ifosfamide, and cisplatin (TIP) vs outcomes with high-dose combination chemotherapy and autologous stem cell transplant for the treatment of patients with relapsed/refractory germ cell tumors.3
“Should we do intensification, spot-based therapy with a different type of therapy, or high-dose chemotherapy with stem cell rescue?” McGregor said. “[TIGER] has been run through the Alliance [for Clinical Trials in Oncology]. It is [an] international trial [that] has completed accrual and we hope to see results at some point in time.”
At a median follow-up of 8.9 years, findings from a retrospective study published in the Journal of Clinical Oncology revealed that patients with germ cell tumors who received TIP after cisplatin-based chemotherapy (n = 104) achieved favorable response rate (FRR) of 79%, including a complete response (CR) rate of 63%.4 The 5-year progression-free survival (PFS) rate was 66% (95% CI, 55%-74%) and the 5-year OS rate was 69% (95% CI, 59%-77%). The 10-year PFS and OS rates were 62% (95% CI, 52%-71%) and 66% (95% CI, 55%-75%), respectively.
Notably, TIP was shown to be effective regardless of a patient’s disease risk status. Those with favorable-risk disease (n = 87) experienced a FRR of 79%, with a 68% CR rate, and those with unfavorable-risk disease (n = 17) achieved a FRR of 76% and a CR rate of 35%. The 10-year PFS rates were 63% (95% CI, 52%-73%) and 59% (95% CI, 33%-78%), respectively. The 10-year OS rates were 68% (95% CI, 56%-77%) and 56% (95% CI, 28%-76%), respectively.
Exploration into novel treatment targets such as Claudin-6 (CLDN6) in patients with relapsed/refractory germ cell tumors is also ongoing. In the phase 1, first-in-human BTN211-01 study (NCT04503278), the investigational agent BTN211, which combines a CLDN6-targeted CAR T-cell therapy with a CAR T-cell amplifying RNA vaccine, is being evaluated in patients with relapsed/refractory advanced solid tumors, including testicular cancer.5
Findings from BTN211-01 published in Nature Medicine demonstrated that patients with CLDN6-positive solid tumors who received BTN211 (n = 21) achieved an unconfirmed overall response rate (ORR) of 33%, including 1 CR. The median duration of response (DOR) was 2.8 months (range, 1.1-10.5) and the disease control rate was 67%. The ORR was 38% among patients with germ cell tumors (n = 13) and the study authors noted that these patients also had the longest DORs.
“I’m excited about the trials that are ongoing for patients with advanced or relapsed disease,” Fam said. “TIGER will help us elucidate whether [the addition of] stem cell therapy to high dose or salvage chemotherapy is going to be beneficial. [I’m also excited about] some of the biomarker testing [research] for following patients with testicular cancer. We have our classic tumor markers, but some of these biomarker assays may help us be more tailored [in our approaches to treatment for] each patient, and to figure out whether they are at a risk for recurrence or need further therapy.”
