Subcutaneous Immunotherapy in Genitourinary Cancer: Clinical Context, Patient Considerations, and Practice Integration

Immunotherapy has become a defining component of treatment for genitourinary cancers, particularly renal cell carcinoma (RCC) and bladder cancer. In RCC, immune checkpoint inhibitors are now embedded across multiple settings, including adjuvant therapy for selected patients after nephrectomy and first-line systemic therapy for advanced disease.  

For clear cell RCC, commonly used first-line approaches include IO/tyrosine kinase inhibitor (TKI) combinations such as pembrolizumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, as well as IO/IO therapy with nivolumab plus ipilimumab, across favorable-risk and poor/intermediate-risk disease groups.¹ 

In bladder cancer, IO has similarly reshaped care across locally advanced, metastatic, perioperative, and maintenance settings. Treatment options for locally advanced or metastatic disease include enfortumab vedotin plus pembrolizumab as a preferred first-line systemic therapy option. Other IO-based strategies include chemotherapy followed by avelumab or nivolumab maintenance therapy, perioperative approaches incorporating durvalumab or pembrolizumab-based regimens, and adjuvant nivolumab or pembrolizumab in selected patients after prior platinum-based neoadjuvant therapy.² 

Among immune checkpoint inhibitors used in GU cancers, SC formulations represent an important evolution in drug delivery. As of April 2026, there are several approved IO therapies for RCC and bladder cancer. All programmed death-ligand inhibitors are administered intravenously, while programmed cell death protein 1 (PD-1) inhibitors pembrolizumab and nivolumab have additional SC formulations.^3-7  

SC nivolumab is one such formulation. SC nivolumab is indicated as first-line monotherapy following combination intravenous (IV) nivolumab plus ipilimumab or in combination with TKIs for advanced RCC, and IV and SC formulations are indicated in urothelial carcinoma settings.⁸ In CheckMate 67T, SC nivolumab was evaluated against IV nivolumab in patients with advanced or metastatic clear cell RCC in a noninferiority study, with comparable pharmacokinetics and safety profiles.^8,9 Use of SC nivolumab in urothelial cancer is supported by evidence from studies conducted with IV nivolumab, together with pharmacokinetic and safety data demonstrating comparable pharmacokinetics and safety profiles between IV and SC formulations.⁸  

SC pembrolizumab is another SC PD-1 formulation available for GU cancers. SC pembrolizumab is indicated in combination with enfortumab vedotin for adults with locally advanced or metastatic urothelial cancer. As a single agent, it can be used for selected locally advanced or metastatic urothelial carcinoma and Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors. It is also indicated for cisplatin-ineligible muscle invasive bladder cancer in combination with enfortumab vedotin as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment. In RCC, SC pembrolizumab is indicated in combination with axitinib or lenvatinib for first-line treatment of advanced RCC and as adjuvant treatment for adult patients at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.¹⁰ The effectiveness of SC pembrolizumab across its approved indications is based on studies with IV pembrolizumab plus study MK-3475A-D77, which demonstrated comparable pharmacokinetics and safety profiles between SC and IV pembrolizumab.^10,11 

One of meaningful considerations in oncology care is time. Patients who mention time burdens may be more likely to decline treatments without an overall survival benefit, regardless of the magnitude of progression-free survival benefit. Patients also cite visit frequency, visit length, treatment duration, transportation, and parking as treatment considerations. The impact of treatment time may extend to quality of life and psychosocial well-being for both patients and care partners. Patients may weigh treatment-related time against expected duration and quality of survival.¹² 

The most immediate patient-facing advantage of SC IO is reduced administration time. SC nivolumab is administered in the abdomen or thigh by a healthcare professional over 3 to 5 minutes.⁸ By contrast, IV nivolumab is administered as a single agent over 30 minutes.⁷ Patient preference data of SC oncology therapies generally suggest that many patients value shorter administration and reduced disruption. CheckMate 8KX, a phase 2/3 study in solid tumors, investigated the pharmacokinetics and safety of SC nivolumab and included exploratory endpoints assessing patient experience and preference. Patient experience and preference were measured using the Patient Experience and Preference Questionnaire, an internally developed, site-administered tool. Patients reported preference for SC nivolumab over IV or had no preference. Most reported that SC administration took less time than expected and did not negatively affect time available to talk with a healthcare professional or interact with others.¹³  

Experience with other SC oncology biologics also supports the potential for reduced administration burden. SC formulations of trastuzumab and rituximab reduced drug administration burden on the healthcare system and were generally preferred by patients and healthcare professionals. SC administration saved an average of 55 minutes of patient chair time compared with IV dosing in prior experience with SC biologics. SC formulations may also simplify dosing, often using fixed-dose regimens rather than bodyweight-adjusted IV dosing, which may improve scheduling flexibility and reduce capacity bottlenecks.¹⁴ SC nivolumab is dosed at either 300 mg per 2.5 mL dose or 600 mg per 5 mL dose.⁷  

For oncology practices, SC IO may introduce operational opportunities as well as implementation considerations. Shorter administration time can reduce infusion chair utilization, improve scheduling flexibility, and allow staff to reserve infusion capacity for therapies that require longer monitoring, complex preparation, or sequential administration. SC oncology therapies have been associated with reduced chair utilization, reduced nursing time per visit, and reduced pharmacy resource utilization.¹⁵ Shorter administration may also reduce clinic burden and support higher patient throughput without requiring expansion of physical space.^15,16 

Successful integration of SC IO may begin with a practical assessment of how patients currently move through the clinic. Practices may need to determine whether SC IO visits are best managed within the infusion suite, an injection clinic, an examination-room workflow, or a hybrid model. These decisions may depend on the size and staffing model of the practice, the number of eligible patients, institutional policies, and the extent to which same-day clinical evaluation is routinely paired with treatment administration. A fast-track model may be appropriate for some stable patients, provided that symptom assessment, toxicity review, and documentation remain integrated into the visit. Faster visits may reduce cancellations or no-shows, and more predictable appointment lengths may contribute to patient confidence. Shorter visits can also provide greater scheduling flexibility and help treatment centers accommodate more same-day add-ons.¹⁷  

Nursing considerations extend beyond the act of giving the injection. Staff may need education on product-specific administration requirements, injection technique, site selection, local reaction assessment, observation practices, and documentation. Because IO-related toxicities can occur across organ systems and may arise at variable points during therapy, the nursing encounter may remain an important opportunity to screen for diarrhea, rash, respiratory symptoms, endocrine changes, hepatic abnormalities, or other signs of immune-related adverse events. In this way, shorter administration time may create an opportunity to redirect part of the visit toward assessment, education, and care coordination. SC administration may also reduce the use of central venous access devices and catheter implantation surgeries in some treatment contexts.^15,18  

Pharmacy and medication-use processes may also need to be adapted as SC IO is incorporated into routine care. For some centers, ready-to-administer SC formulations may streamline workflows, reduce compounding time, and decrease sterile preparation workload, which may improve pharmacy efficiency and turnaround time.¹⁵ These potential efficiencies may be most fully realized when pharmacy, nursing, scheduling, and oncology teams align on patient eligibility, visit timing, drug availability, and documentation requirements. 

Patient education may also benefit from a deliberate, consistent approach. Patients transitioning from IV to SC therapy may have questions about whether a shorter administration time changes the strength, seriousness, or expected activity of treatment. Others may want to understand what the injection will feel like, where it will be given, how long they will be monitored, and what local or systemic symptoms they may experience afterward. Clinicians may wish to explain that SC administration represents a different delivery route for an established IO therapy and that available data support comparability between SC and IV nivolumab in the studied setting.^8,9 This discussion may help reassure patients that reduced time in the clinic does not necessarily mean reduced attention to efficacy, safety, or monitoring. 

1. Vano YA, Ladoire S, Elaidi R, et al. First-line treatment of metastatic clear cell renal cell carcinoma: what are the most appropriate combination therapies? Cancers (Basel). 2021;13(21):5548. doi:10.3390/cancers13215548
2. Moon HH, Kirker M, Abraham A, et al. Noninterventional retrospective study of standard-of-care systemic treatment patterns and outcomes in US patients with advanced urothelial carcinoma. Oncologist. 2025;30(7):oyaf071. doi:10.1093/oncolo/oyaf071
3. Bavencio. Prescribing information. EMD Serono Inc; 2025.
4. Imfinzi. Prescribing information. AstraZeneca Pharmaceuticals; 2025.
5. Tecentriq. Prescribing information. Genentech Inc; 2026.
6. Ketruda. Prescribing information. Merck & Co; 2026.
7. Opdivo. Prescribing information. Bristol Myers Squibb Company; 2026.
8. Opdivo Qvantig. Prescribing information. Bristol Myers Squibb Company; 2025.
9. Albiges L, Bourlon MT, Chacón M, et al. Subcutaneous versus intravenous nivolumab for renal cell carcinoma. Ann Oncol. 2025;36(1):99-105. doi:10.1016/j.annonc.2024.09.002 
10. Ketruda Qlex. Prescribing information. Merck & Co; 2026.
11. Felip E, Rojas CI, Schenker M, et al. Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial. Ann Oncol. 2025;36(7):775-785.  doi:10.1016/j.annonc.2025.03.012 
12. Gupta A, Brundage MD, Galica J, et al. Patients’ considerations of time toxicity when assessing cancer treatments with marginal benefit. Oncologist. 2024;29(11):978-985. doi:10.1093/oncolo/oyae187 
13. Lonardi S, Ługowska I, O’Donnell A, et al. Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study. J Immunother Cancer. 2025;13:e011918. doi:10.1136/jitc-2025-011918 
14. Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425-440. doi:10.1007/s40259-018-0295-0 
15. McCloskey C, Toboso Ortega M, Nair S, et al. A systematic review of time and resource use costs of subcutaneous versus intravenous administration of oncology biologics in a hospital setting. PharmacoEconomics Open. 2023;7:3-36. doi:10.1007/s41669-022-00361-3
16. George S, Bourlon MT, Overman MJ, et al. Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: a clinical, economic and patient perspective. Cancer Treat Rev. 2025;139:102974. doi:10.1016/j.ctrv.2025.102974
17. Epstein RS. Payer perspectives on intravenous versus subcutaneous administration of drugs. Clinicoecon Outcomes Res. 2021;13:801-807. doi:10.2147/CEOR.S317687
18. Nuzzo PV, Pond GR, Abou Alaiwi S, et al. Conditional immune toxicity rate in patients with metastatic renal and urothelial cancer treated with immune checkpoint inhibitors. J Immunother Cancer. 2020;8(1):e000371. doi:10.1136/jitc-2019-000371