Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.

BACKGROUND: No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma. METHODS: We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight intravenously on days 1 and 8) and pembrolizumab (at a dose of 200 mg intravenously on day 1) (enfortumab vedotin-pembrolizumab group) or gemcitabine and either cisplatin or carboplatin (determined on the basis of eligibility to receive cisplatin) (chemotherapy group). The primary end points were progression-free survival as assessed by blinded independent central review and overall survival. RESULTS: A total of 886 patients underwent randomization: 442 to the enfortumab vedotin-pembrolizumab group and 444 to the chemotherapy group. As of August 8, 2023, the median duration of follow-up for survival was 17.2 months. Progression-free survival was longer in the enfortumab vedotin-pembrolizumab group than in the chemotherapy group (median, 12.5 months vs. 6.3 months; hazard ratio for disease progression or death, 0.45; 95% confidence interval [CI], 0.38 to 0.54; P<0.001), as was overall survival (median, 31.5 months vs. 16.1 months; hazard ratio for death, 0.47; 95% CI, 0.38 to 0.58; P<0.001). The median number of cycles was 12 (range, 1 to 46) in the enfortumab vedotin-pembrolizumab group and 6 (range, 1 to 6) in the chemotherapy group. Treatment-related adverse events of grade 3 or higher occurred in 55.9% of the patients in the enfortumab vedotin-pembrolizumab group and in 69.5% of those in the chemotherapy group. CONCLUSIONS: Treatment with enfortumab vedotin and pembrolizumab resulted in significantly better outcomes than chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma, with a safety profile consistent with that in previous reports. (Funded by Astellas Pharma US and others; EV-302 ClinicalTrials.gov number, NCT04223856.).

Drug extravasation with Enfortumab vedotin.

INTRODUCTION: Enfortumab vedotin is an antibody drug conjugate approved for management of pretreated locally advanced or metastatic urothelial carcinoma, which is associated with a rare risk of drug extravasation and soft tissue reactions. CASE REPORT: We report two cases of EV extravasation with subsequent development of bullae and cellulitis. MANAGEMENT AND OUTCOME: They were both treated for cellulitis and had conservative management without surgical intervention and were able to resume treatment with Enfortumab vedotin without subsequent adverse events. DISCUSSION: We propose that EV acts as a vesicant upon extravasation, highlight measures to prevent extravasation events, and encourage appropriate measures when dealing such as attempt of aspiration, removal of catheter, application of compresses, and thorough documentation with photographic evidence.

Use of enfortumab vedotin in an HIV-positive patient with urothelial carcinoma.

INTRODUCTION: Enfortumab vedotin is an antibody-drug conjugate used in patients with pretreated advanced urothelial carcinoma. Patients with human immunodeficiency virus were excluded from clinical trials conducted with this agent. Efficacy and safety of enfortumab vedotin has not been established in this patient population. CASE REPORT: A patient with a long-standing diagnosis of human immunodeficiency virus and an undetectable viral load on antiretroviral therapy was diagnosed with metastatic upper tract urothelial carcinoma. Following disease progression on platinum-based chemotherapy and pembrolizumab, he was initiated on therapy with enfortumab vedotin. MANAGEMENT & OUTCOME: The patient developed significant toxicity shortly after initiation of enfortumab vedotin. His treatment was subsequently changed to docetaxel chemotherapy and he developed similar significant toxicity. Upon changing his antiretroviral therapy regimen, he was rechallenged with enfortumab vedotin and was able to tolerate it without dose-limiting toxicity, ultimately achieving a partial treatment response. DISCUSSION: This case describes use of enfortumab vedotin in a patient with human immunodeficiency virus, which has not previously been reported. It also underscores the importance of careful medication reconciliation in patients receiving enfortumab vedotin and antiretroviral therapy.

Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab.

INTRODUCTION: Prognosis for patients with lymph node positive or metastatic penile squamous cell carcinoma remains poor. Chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen) is recommended as a first-line option in this cohort of patients. No standard preferred subsequent-line therapy exists for patients with relapsed or refractory penile carcinoma following TIP chemotherapy. Molecular pathogenesis of penile cancer can be subdivided into human papilloma virus-dependent and human papilloma virus-independent pathways. Recent studies have demonstrated increased expression of programmed death ligand-1 in some penile tumors, commonly those that are human papilloma virus-negative. Given the rarity of penile carcinoma in industrialized countries and lack of effective therapies, checkpoint inhibitors may be an attractive treatment option for this subset of patients. CASE REPORT: We report a case of metastatic penile cancer refractory to TIP chemotherapy, with a dramatic treatment response to ipilimumab and nivolumab. Molecular profiling of this tumor showed a high programmed death ligand-1 expression, high tumor mutational burden, high microsatellite instability, and alterations in DNA mismatch repair genes. DISCUSSION: This case highlights another dimension of information that may be gained with molecular genomic profiling of penile tumors, providing insight into the biologic behavior of this neoplasm and assessing for predictive biomarkers of response to immune checkpoint inhibitors.

Adjuvant pembrolizumab in genomically selected high-risk patients with muscle-invasive bladder cancer.

INTRODUCTION: Patients with muscle-invasive urothelial bladder cancer post neoadjuvant cisplatin-based chemotherapy with pathologic advanced disease (ypT3, ypT4, ypN+) at radical cystectomy have a significantly worse five-year overall survival. There is currently no preferred adjuvant therapy to reduce risk of cancer recurrence in this high-risk patient cohort and surveillance remains the standard-of-care. CASE REPORT: We present a case series of two patients who received cisplatin-based neoadjuvant chemotherapy and had pathologic node-positive urothelial carcinoma at the time of radical cystectomy. Tumor next generation sequencing revealed high mutational burden in both patients and positive PD-L1 in one patient.Management and outcome: Patients were treated with adjuvant pembrolizumab and experienced long-term disease free intervals. DISCUSSION: Use of adjuvant checkpoint inhibitors in patients post neoadjuvant cisplatin-based chemotherapy with pathologic advanced disease at the time of radical cystectomy at high-risk of cancer recurrence sounds appealing. Careful patient selection based on tumor-specific genomic alterations may be key. Large trials addressing this question are ongoing.

Development of carpal tunnel syndrome in association with checkpoint inhibitors.

INTRODUCTION: The incidence of neuropathy with checkpoint inhibitors is 0.3-1%, typically occurring 2-12 weeks after treatment initiation. Common neuropathy phenotypes include inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculopathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis. Carpal tunnel syndrome is the most common entrapment neuropathy in the general population; however, the association of carpal tunnel syndrome with checkpoint inhibitors is exceedingly rare. CASE REPORT: We report two cases of patients with no prior history of carpal tunnel syndrome treated with checkpoint inhibitors that developed de novo bilateral carpal tunnel syndrome.Management & Outcome: For both patients, the neurologic symptoms improved with cessation of the checkpoint inhibitor and initiation of corticosteroids. DISCUSSION: Given the prevalence of carpal tunnel syndrome in the general population, a high index of suspicion for carpal tunnel in patients receiving checkpoint inhibitors and prompt treatment with corticosteroids is essential.

Dual HER2 Blockade in Non-Small Cell Lung Cancer Harboring a HER2 Mutation.

Identification of targetable oncogenic mutations in non-small cell lung cancer (NSCLC) has been a major advance in cancer treatment. Laboratory techniques to assess human epidermal growth factor receptor 2 (HER2) positivity in NSCLC include immunohistochemistry (IHC) for protein overexpression, fluorescent in situ hybridization (FISH) for gene amplification, and next generation sequencing (NGS) for HER2 gene mutations. These tests have a controversial prognostic and predictive value, with an emerging association between HER2 gene mutations and treatment response to HER2 targeted therapy. We present a case of a woman with metastatic lung adenocarcinoma with HER2 positivity assessed by IHC and FISH, as well as a high gene copy number noted on NGS. She was observed to have significant disease progression following standard first-line platinum doublet chemotherapy. She was started on dual HER2 blockade in the second-line setting, which yielded a great response in the liver with stable disease elsewhere. To our knowledge, this is the first report describing successful use of dual HER2 blockade in metastatic HER2 positive NSCLC. We also review common laboratory techniques for determining HER2 positivity in NSCLC and their clinical applications.

Recurrent thrombosis prevention with intravenous immunoglobulin and hydroxychloroquine during pregnancy in a patient with history of catastrophic antiphospholipid syndrome and pregnancy loss.

We report a case of a 36-year old patient with prior history of thrombosis in a setting of antiphospholipid antibody syndrome (APS) as well as pregnancy-associated catastrophic antiphospholipid syndrome (CAPS), resulting in multi-organ infarction and pregnancy loss. The episode of CAPS occurred while she was receiving antepartum low-dose aspirin and therapeutic-dose enoxaparin. This patient presented again at 6 weeks gestation and ultrasounds were consistent with fetal growth restriction, concerning for placental insufficiency and thrombosis. This time, hydroxychloroquine and monthly intravenous immunoglobulin (IVIG) infusions were added to her prophylaxis regimen, resulting in a successful delivery. Platelet count and antiphospholipid antibody titers were routinely monitored throughout pregnancy as markers of disease activity for APS. Current thromboprophylaxis guidelines do not address therapeutic options to prevent further pregnancy morbidity in women who develop recurrent episodes of thrombosis or CAPS despite receiving adequate anti-thrombotic treatment. Use of hydroxychloroquine and IVIG has been associated with good outcomes in this subset of patients.

A case report of challenges in distinguishing gastroesophageal junction hepatoid adenocarcinoma from testicular germ cell tumor: Insights for improved diagnosis with gene expression profiling.

Gastroesophageal junction hepatoid adenocarcinoma is a rare form of gastroesophageal cancer. We present a case of a 38-year-old man with no significant medical history who was diagnosed with gastroesophageal junction hepatoid adenocarcinoma but initially misdiagnosed with a testicular germ cell tumor, given the elevated alpha-feto protein and poorly differentiated pathology. We will elaborate on the importance of gene expression profiling in modern oncology to better define the tumor of origin in patients with cancer of unknown primary origin, how it helped us to diagnose gastroesophageal junction hepatoid adenocarcinoma and how it can help identify potential additional therapeutic targets in some cases. Due to the rarity of this subtype of gastroesophageal junction cancer there is a lack of standard therapeutic options, and we will discuss the most commonly used treatment regimens. The patient underwent three lines of antineoplastic therapy and unfortunately passed after 51 weeks of follow-up.

Use of Radiation Therapy for Ataxia-Telangiectasia Mutated (ATM)-Mutation Metastatic Renal Cell Carcinoma: A Case Report.

Papillary renal cell carcinoma (pRCC) is a rare kidney cancer with limited treatment options and poor outcomes when metastatic. We present a case of a 42-year-old male with metastatic pRCC harboring a somatic ataxia-telangiectasia mutated (ATM) mutation who was treated at our institution. After progression of disease (POD) on ipilimumab/nivolumab, followed by POD on cabozantinib, the patient was treated with radiation therapy to metastatic cervical lymphadenopathy to 60 Gy in 15 fractions as well as retroperitoneal lymphadenopathy to 36 Gy in 9 fractions, which was curtailed due to intolerance. This was followed by sequential systemic therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor and pembrolizumab, which was also discontinued due to adverse effects. Despite not receiving any treatment for 10 months, his disease remains stable. We believe that the prolonged progression-free survival of this patient with ATM-mutation metastatic pRCC is likely due to the enhanced sensitivity of the tumor to radiation therapy due to ATM loss.

Therapy With Metronomic Cyclophosphamide (mCyc) for Previously-Treated Metastatic Castrate-Resistant Prostate Cancer (mCRPC).

INTRODUCTION: Despite the introduction of various novel therapies for management of metastatic castrate resistant prostate cancer (mCRPC) in recent decades, available treatment options are finite and remain limited. Multiple historical studies have demonstrated activity and a favorable toxicity profile of oral metronomic cyclophosphamide (mCyc) in prostate cancer (PCa). Unlike the cytotoxic immunosuppressive effects of high-dose intravenously-administered cyclophosphamide, continuous low doses of oral mCyc have a unique immune-stimulatory mechanism of action. MATERIALS AND METHODS: This is a retrospective, multi-institution study of men with 43 patients with mCRPC treated mCyc. Patient demographic information as well as clinical, pathologic, and genomic characteristics of their PCa were extracted. The primary endpoint was the rate of PSA decline by ≥ 50% (ie, PSA50). Additional efficacy and toxicity data as well as cost analysis compared to other commonly used agents in mCRPC was obtained. RESULTS: PSA50 was noted in 20.9% of patients, while an additional 25.6% patients achieved < PSA50 and 6.9% reported improvement in prostate cancer-related symptoms without any PSA reduction. Meanwhile, 9.3% of patients required mCyc dose reduction, 11.6% needed dose interruption due to toxicity, and no treatment discontinuations due to toxicity were observed. mCyc was also cost effective compared to other agents commonly used in mCRPC. CONCLUSIONS: Despite the small sample size and retrospective nature of this dataset, mCyc demonstrated promising rapid activity and a tolerable toxicity profile in a heavily pretreated mCRPC population with aggressive clinical, pathologic, and genomic disease features.

The Role of Maximal TURBT in Muscle-Invasive Bladder Cancer: Balancing Benefits in Bladder Preservation and Beyond.

Radical cystectomy with lymph node dissection and urinary diversion is the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC). However, in patients who refuse cystectomy, or in whom cystectomy carries a high risk, bladder-preserving therapies remain potential options. Bladder preservation therapies can include maximal debulking transurethral resection of bladder tumor (TURBT), concurrent chemoradiation therapy, followed by cystoscopy to assess response. At this time, maximal TURBT is recommended for patients prior to the initiation of chemoradiation therapy or in patients with residual bladder tumors after the completion of chemoradiation therapy. That being said, TURBT carries significant risks such as bladder perforation, bleeding, and infection, ultimately risking delayed systemic treatment. Hence, understanding its role within trimodal therapy is crucial to avoid undue suffering in patients. Herein, we review the current literature on the impact of debulking TURBT in non-metastatic MIBC.

Socioeconomic Barriers to Receiving Early Salvage Radiotherapy for Locally Advanced Prostate Adenocarcinoma: A Retrospective Single-Center Study.

Purpose This study aimed to identify factors associated with delays in initiating early salvage radiation therapy in prostate cancer patients with prostate-specific antigen (PSA) failure after prostatectomy. Methods We conducted a single-institution, retrospective study of patients receiving salvage radiation therapy after radical prostatectomy from 2011 to 2022. Patient demographics and clinical data were examined to identify factors that may have influenced the time to start of radiation therapy after surgery. Utilizing a PSA cut off of 0.25 ng/ml or less, we classified patients as receiving either early "PSA low" or late "PSA high" salvage therapy depending on their PSA at the time of initiating treatment. Results Of the 81 patients evaluated, the median age was 61.9 years (IQR 57.9 - 66.5), with most presenting with pT3 (65.4%), Grade Group 2 disease (35.8%), and positive margins 55%). Median PSA at salvage radiation therapy commencement was 0.30 ng/mL (0.18 - 0.48). 40 patients completed early salvage and 41 patients completed late salvage in the overall cohort. A significant association was found between patient insurance carrier and pre-radiation PSA levels. Patients with HMO (Health Maintenance Organization) or PPO (Preferred Provider Organization) insurance were more likely to complete late salvage radiation compared to non-managed Medicare patients (HMO OR 4.0, p <0.05 & PPO OR 3.3 p <0.05 vs non-managed Medicare). All uninsured patients in the cohort received late salvage radiation. Conclusions Insurance type was significantly associated with the timing of salvage radiation therapy post-prostatectomy, suggesting a relationship with providers requiring prior authorization (HMO and PPO coverage). This study supports proper PSA surveillance, in particular for those with HMO or PPO coverage.

Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab.

PURPOSE: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K. METHODS: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms. RESULTS: Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24. CONCLUSION: EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.

Pembrolizumab plus Abiraterone Acetate and Prednisone in Patients with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort D.

BACKGROUND AND OBJECTIVE: Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC. METHODS: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide. Patients received pembrolizumab 200 mg intravenously every 3 wk plus abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily. The primary endpoints were safety, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3-modified RECIST v1.1 by BICR and overall survival (OS). KEY FINDINGS AND LIMITATIONS: For the 103 patients who were treated, median follow-up was 28 mo (interquartile range 26-31). The confirmed PSA response rate was 56% (58/103 patients). The ORR for patients with RECIST v1.1-measurable disease was 16% (6/37 patients). Median rPFS was 15 mo (95% confidence interval 9.2-22) and median OS was 30 mo (95% confidence interval 23-not reached); the estimated 24-mo OS rate was 58%. In total, 91% of patients experienced treatment-related adverse events, and 39% experienced grade 3-5 events. Grade 3/4 elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 12% and 6.8% of patients, respectively. One patient died due to treatment-related myasthenic syndrome. Study limitations include the single-arm design. CONCLUSIONS: Pembrolizumab plus abiraterone and prednisone demonstrated antitumor activity and acceptable safety in patients with chemotherapy-naïve mCRPC. Higher incidence of grade 3/4 elevated ALT/AST occurred than was reported for the individual agents. PATIENT SUMMARY: For patients with metastatic castratation-resistant prostate cancer, the drug combination of pembrolizumab plus abiraterone and prednisone showed antitumor activity and acceptable safety.

Results from a Phase 1b/2 Study of Ibrutinib Combination Therapy in Advanced Urothelial Carcinoma.

Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. We evaluated the safety and efficacy of ibrutinib, alone or combined with standard-of-care regimens, in adults with advanced urothelial carcinoma (UC). Once-daily ibrutinib was administered orally at 840 mg (single-agent or with paclitaxel) or at 560 mg (with pembrolizumab). Phase 1b determined the recommended phase 2 dose (RP2D) of ibrutinib, and phase 2 assessed progression-free survival (PFS), overall response rate (ORR), and safety. Thirty-five, eighteen, and fifty-nine patients received ibrutinib, ibrutinib plus pembrolizumab, and ibrutinib plus paclitaxel at the RP2D, respectively. Safety profiles were consistent with those of the individual agents. The best-confirmed ORRs were 7% (two partial responses) with single-agent ibrutinib and 36% (five partial responses) with ibrutinib plus pembrolizumab. Median PFS was 4.1 months (range, 1.0-37.4+) with ibrutinib plus paclitaxel. The best-confirmed ORR was 26% (two complete responses). In previously treated patients with UC, ORR was higher with ibrutinib plus pembrolizumab than with either agent alone (historical data in the intent-to-treat population). ORR with ibrutinib plus paclitaxel was greater than historical values for single-agent paclitaxel or ibrutinib. These data warrant further evaluation of ibrutinib combinations in UC.

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer.

PURPOSE: Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting. PATIENTS AND METHODS: In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms. RESULTS: The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%). CONCLUSION: EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.

Late recurrence of localized pure seminoma in prostate gland: A case report.

BACKGROUND: Late relapses of early-stage germ cell tumors are rare. Most patients (-85%) with stage I seminoma are cured by radical orchiectomy. The detection of late relapse is challenging given the relative rarity of this phenomenon, and the fact that patients who have completed surveillance are usually not undergoing regular oncologic workup nor imaging. While many treatment options do exist for a patient with late relapse of seminoma, surgery is typically the mainstay as these tumors are generally thought to be more chemo-resistant. CASE SUMMARY: In this article, we describe the management of a patient with an early-stage pure seminoma who was subsequently identified to have a recurrence two decades later. We provide a review of the literature not only focused on clinical factors and biology, but also the management of late recurrences specifically in pure seminoma and in prostate gland. CONCLUSION: There is a paucity of data and treatment recommendations for this clinical entity, and a multidisciplinary approach emphasizing subspecialty expert consultation and patient education is imperative.

Combination of Pembrolizumab and Stereotactic Body Radiation Therapy in Recurrent Metastatic Penile Squamous Cell Carcinoma: A Case Study.

The prognosis for patients with penile squamous cell carcinoma metastatic to regional lymph nodes or distant sites remains poor with limited treatment options, especially after the failure of first-line chemotherapy. Clinical trials evaluating the use of checkpoint inhibitor therapy, or the use of checkpoint inhibitor therapy with stereotactic body radiation therapy for the treatment of metastatic penile squamous cell carcinoma, are currently unavailable. In this case report, we present a patient with relapsed advanced penile squamous cell carcinoma and an unknown (human papilloma virus) HPV status and borderline programmed death-ligand 1 (PD-L)1 status who was treated with pembrolizumab and stereotactic body radiation therapy. This patient achieved a complete durable treatment response despite having genomic features of an immunologically "cold" tumor. This case highlights the importance of investigating more into the treatment of these tumors that lack genomic features that classically have been observed to be susceptible to treatment with immunotherapy or immunotherapy augmented with stereotactic body radiation therapy in solid tumors, particularly in metastatic penile squamous cell carcinoma.

Use of immunotherapy in clinical management of genitourinary cancers - a review.

Checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 have revolutionized oncologic care delivery, including clinical management of genitourinary malignancies. Despite significant associated improvement in patient outcomes, molecular heterogeneity of tumors, variable tumor engagement with the immune response, and unique patient factors likely account for different clinical responses to immunotherapy agents. A search for predictive biomarkers of treatment response to checkpoint inhibitors is underway and several candidates, although imperfect, have been identified. Multiple checkpoint inhibitors have received approval as monotherapies or in combination with other agents in genitourinary cancers and clinical trial data continues to rapidly evolve. This review summarizes key published evidence involving use of checkpoint inhibitors in management of urothelial carcinoma, renal cell carcinoma, prostate adenocarcinoma, and penile squamous cell carcinoma. This review aims to help oncology practitioners develop an up-to-date, evidence-based approach to using these agents when managing patients with genitourinary cancers in clinical practice.