Dr Garje on Clinical Outcomes With Multimodal Approaches in Invasive Primary Urethral Cancer

“Patients with these cancers have an aggressive disease with limited treatment options. When they are diagnosed, it’s always important to have multidisciplinary collaboration between medical oncology, radiation oncology, and surgeons to come up with the best treatment approach for these patients.”

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, discusses findings from a real-world study that evaluated clinical outcomes among patients with invasive primary urethral cancer (PUC) of varying histologies who received various treatment approaches. 

Garje and colleagues conducted a real-world, multi-institutional study to examine treatment patterns and clinical outcomes for patients with PUC, a rare and aggressive malignancy without an established treatment approach. Due to the absence of prospective studies in this patient population, the optimal management strategy for PUC remains unclear, according to Garje. This study sought to address this gap by analyzing different treatment modalities and their associated outcomes, he says.

 demonstrated significant variability in treatment approaches, with patients receiving surgery alone; radiation alone; neoadjuvant chemotherapy followed by surgery; or a more intensive multimodal regimen combining chemotherapy, radiation, and surgery, Garje details. Despite this treatment heterogeneity, findings indicated that patients who received multimodal therapy had improved disease-free survival compared with those treated with a single modality, he reports. Importantly, no differences in outcomes were observed based on sex or histology, Garje notes.

These findings underscore the necessity of a multidisciplinary approach to optimize treatment outcomes in patients with PUC, Garje says. Given the aggressive nature of the disease and the lack of standardized treatment guidelines, close collaboration between medical oncologists, radiation oncologists, and surgeons is essential to develop individualized treatment strategies, he emphasizes. Future research should focus on prospective studies to refine treatment recommendations and establish evidence-based guidelines for managing this rare malignancy, he concludes.

Videos

Rohan Garje, MD, discusses clinical outcomes among patients with invasive primary urethral cancer based on varying treatment approaches and histology. 

Dr Garje on Unmet Needs in Small Cell Bladder Cancer

“Most of the data that we use for the treatment of [patients with] small cell carcinoma arising from any part of the body, other than lung, is extrapolated from small cell lung cancer, so there are limited clinical trials and prospective studies [in this setting]. [Therefore,] it is important for us to use retrospective data from large databases to see how patients fare [with various] treatment choices and see if that can improve their outcomes.”

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, discusses the unmet needs for patients with small cell bladder cancer and the rationale for investigating the effect of different treatment modalities on survival outcomes in patients with locoregional disease.

Small cell bladder carcinoma is a rare and aggressive malignancy with limited treatment data, and most therapeutic approaches in small cell carcinomas broadly are extrapolated from small cell lung cancer due to the paucity of dedicated clinical trials or prospective studies in other tumor types, Garje begins. This lack of direct evidence presents challenges for oncologists in determining optimal treatment strategies for this patient population, he states. Real-world data and large retrospective analyses are thus critical in understanding treatment outcomes and guiding management in this patient population, Garje emphasizes.

Accordingly, Garje and colleagues conducted a retrospective national study evaluating the effects of various treatment modalities on survival outcomes in patients with locoregional small cell bladder carcinoma (T1-T4, N0-N3, M0). The study used data from a nationwide registry and analyzed outcomes based on different therapeutic approaches. Results presented at the 

 demonstrated that patients who received perioperative chemotherapy, either in the neoadjuvant or adjuvant setting, combined with definitive cystectomy or partial cystectomy, had improved survival outcomes compared with patients treated with other modalities. These findings underscore the importance of incorporating perioperative chemotherapy with surgical intervention in the management of locoregional small cell bladder carcinoma, Garje concludes.

Rohan Garje, MD, discusses the unmet needs for patients with small cell bladder cancer.

Dr Garje on the Benefits of Multimodal Treatment in Small Cell Bladder Cancer

Rohan Garje, MD, chief, of Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, discusses the benefits of a multimodal approach for the treatment of patients with small cell bladder cancer.

Garje and colleagues presented results from a national study at the 

 exploring the impact of different treatment modalities on the survival outcomes of patients with small cell bladder cancer using data from a nationwide registry. The retrospective study included patients with locoregional small cell bladder cancer (T1-T4, N0-N3, M0).

Garje explains that patients who received the perioperative chemotherapy in either the neoadjuvant or adjuvant setting in combination with definitive cystectomy or partial cystectomy, had better survival outcomes compared with other treatment modalities. Patients treated with perioperative systemic therapy with definitive surgery experienced a median overall survival (OS) of 64.49 months. Patients given perioperative systemic therapy plus concurrent chemoradiation had a median OS of 29.27 months. Those who had surgery alone experienced a median OS of 14.13 months. The median OS was 21.29 months for those given systemic therapy alone, and the median OS was 7.82 months for patients given radiotherapy alone.

Notably, perioperative systemic therapy in combination with surgery was associated with a 54% reduction in the risk of death compared with surgery alone (HR, 0.46; 95% CI, 0.37-0.58). Systemic therapy plus concurrent chemoradiation was linked to a 41% reduction in the risk of death vs surgery alone (HR, 0.59; 95% CI, 0.47-0.73).

These results showed patients receiving single-modality therapies—such as surgery, radiation therapy, or systemic therapy—were associated with lower survival , Garje notes. For clinicians treating patients with small cell bladder carcinoma, Garje emphasizes the most positive outcomes that have been observed in this database was from patients who received chemotherapy along with definitive surgery.

Moreover, further research and clinical trials are essential to continue refining and enhancing multimodal treatment strategies for this patient population, Garje concludes.

Rohan Garje, MD, discusses the benefits of a multimodal approach for patients with small cell bladder cancer. 

Rohan Garje, MD, discusses the impact of human papillomavirus status on survival outcomes in penile squamous cell carcinoma.

Dr Garje on the Prognostic Value of HPV Status for Survival Outcomes in pSCC

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, discusses the impact of human papillomavirus (HPV) infection on survival outcomes for patients with penile squamous cell carcinoma (pSCC), according to findings from the National Cancer Database.

Although patients with pSCC have a risk profile and clinical course similar to that of other SCCs, the impact of HPV status on survival in pSCC remains uncertain, Garje begins.

To elucidate this, a retrospective study of median overall survival (OS) in patients with pSCC according to HPV status was conducted using the National Cancer Database, Garje states. The study identified a total of 1,371 men with penile cancer who were tested for HPV between 2004 and 2021, Garje details. Among them, 39.3% had HPV-positive disease, and 60.7% did not have an HPV infection. This distribution was irrespective of the stage, as all patients from stage I to stage IV were included, he notes, adding that patients were then subdivided into 2 groups based on HPV status.

Results from this analysis were presented at the 

 and indicated that HPV infection in patients with pSCC is associated with improved survival, regardless of factors such as age, comorbidities, stage, and treatment modality, Garje reports. These modalities included systemic therapy, surgery alone, chemotherapy, and radiation therapy, he adds. HPV infection was linked to a 21% reduction in the risk of death (HR, 0.79; 95% CI, 0.65-0.98; 

 = .03), and the median OS for men with HPV-negative disease was 104.38 months (95% CI, 89.1- 115.98), compared to 123.96 months (95% CI, 98.96- 148.4; 

 = .01) for those with HPV-positive pSCC.

These findings highlight HPV status as a significant prognostic indicator for patients with pSCC, irrespective of their clinical profile, Garje says. Accordingly, routine testing for HPV at the time of diagnosis should be performed in patients with pSCC to better inform potential treatment strategies, he concludes.

Dr Garje on Emerging Biomarkers in mCRPC

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute,

and the approaches that are being developed

 to target them in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as where the treatment field for this patient population is headed.

Novel biomarkers, such as STK1 and DLL3, have been identified as unique to prostate cancer, providing new targets for therapeutic intervention, Garje begins. Theragnostics, a combination of therapy and diagnostics, is one promising approach being developed to target these biomarkers, according to Garje. This method identifies the presence of cancerous cells and delivers targeted treatment to those cells, enhancing the specificity and efficacy of the treatment, he explains.

Additionally, the use of bispecific T-cell engagers and monoclonal antibodies offers another avenue for targeting these biomarkers, Garje continues. Recent studies have shown promising results in using bispecific T-cell engagers in later-line treatments for prostate cancer, indicating their potential to significantly impact patient outcomes, he explains. However, Garje notes some challenges to address, particularly concerning the toxicity profiles of these drugs. Cytokine release syndrome is a notable adverse effect and can be particularly harmful to elderly patients who often cannot tolerate intensetreatments, Garje reports.

Looking to the future, the field of cancer treatment is heading toward several exciting developments, Garje emphasizes. In radiotheragnostics, new agents, such as Actinium-225, Thorium-229, and Copper-64/65 are being explored, offering potentially more effective options for targeting cancer cells with radiation, he states. Another promising area is the development of CAR T-cell therapies, Garje explains. Although still in the early phases of research, there is significant enthusiasm around the potential of CAR T-cell therapies to revolutionize cancer treatment by harnessing the body’s own immune system to fight cancer, Garje says.

Bispecific T-cell engagers continue to be rapidly tested, and new treatment modalities, such as androgen receptor degraders, are being investigated, he expands. These degraders could provide benefits to patients who have developed resistance to androgen receptor pathway inhibitors, potentially improving outcomes by degrading the androgen receptors themselves. The next 5 to 10 years are expected to bring rapid advancements in these areas, Garje concludes.

Rohan Garje, MD, discusses emerging biomarkers in metastatic castration-resistant prostate cancer and where the treatment field is headed.

Dr Garje on the Utility of Lu 177 Vipivotide Tetraxetan in mCRPC

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, 

discusses the utility of lutetium Lu 177 vipivotide tetraxetan

 (formerly known as 177Lu-PSMA-617) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Lutetium Lu 177 vipivotide tetraxetan has established itself as a standard of care (SOC) in the treatment of patients with mCRPC, particularly in later lines of therapy following androgen receptor pathway inhibitors (ARPIs) and chemotherapy, Garje begins. However, ongoing research is exploring avenues to expand its use and optimize treatment outcomes. One direction of investigation involves moving this agent into earlier lines of therapy, prior to the initiation of chemotherapy, she explains. The phase 3 PSMAfore trial (NCT04689828) investigated this approach and demonstrated a significant progression-free survival (PFS) benefit with lutetium Lu 177 vipivotide tetraxetan compared with switching to another ARPI, Garje reports, saying that this shift toward earlier use of the radioligand reflects efforts to enhance treatment efficacy.

Additionally, there is growing interest in evaluating lutetium Lu 177 vipivotide tetraxetan in the first-line setting of mCSPC, she expands. The ongoing PSMAddition trial (NCT04720157) has recently completed enrollment, and the results of this study will provide valuable insights into the efficacy and safety of this radioligand in earlier stages of prostate cancer treatment, he elucidates. The movement of radioligands into earlier lines of therapy underscores the evolution of prostate cancer management and the quest for more effective treatment options across different disease stages, Garje explains.

In parallel, researchers are exploring combination strategies to maximize the therapeutic potential of lutetium Lu 177 vipivotide tetraxetan, he continues. Studies are investigating its use in combination with immunotherapy agents, PARP inhibitors, chemotherapy, and radiation therapy with the goal of enhancing treatment responses and durability. Despite the benefits with this radioligand observed in studies such as the phase 3 VISION trial (NCT03511664), there remains a need to address the issue of response durability, Garje notes. Identifying predictive biomarkers to select patients who will benefit most from this therapy and exploring novel combination approaches are critical steps toward achieving more durable and impactful treatment outcomes for patients with metastatic prostate cancer, he concludes.

Rohan Garje, MD, discusses the utility of lutetium Lu 177 vipivotide tetraxetan in metastatic castration-resistant prostate cancer.

Dr Garje on Selecting Between PARP Inhibitor Combinations in mCRPC

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Baptist Health Miami Cancer Institute, discusses considerations when choosing between FDA-approved PARP inhibitor–based combinations for patients with metastatic castration-resistant prostate cancer (mCRPC).

Notable treatment modality advancements have emerged for patients with mCRPC, Garje says. The phase 3 MAGNITUDE trial (NCT03748641) investigated the combination of niraparib (Zejula) and abiraterone acetate (Zytiga). Similarly, the phase 3 TALAPRO-2 trial (NCT03395197) explored talazoparib (Talzenna) in combination with enzalutamide (Xtandi), and the phase 3 PROpel trial (NCT03732820) assessed olaparib (Lynparza) plus abiraterone acetate. These trials collectively evaluated the efficacy of PARP inhibitors in combination with androgen receptor pathway inhibitors in the first-line mCRPC setting, and their outcomes emphasize the importance of patient selection to optimize treatment outcomes, Garje explains.

All 3 studies successfully met their primary end point of radiographic progression-free survival, and demonstrated overall survival (OS) benefits with the PARP inhibitors. Patients harboring 

 mutations derived the greatest OS benefit from these combinations, Garje emphasizes. The findings from these studies supported the FDA approvals of their respective regimens, Garje notes.

It is crucial to discern the specific patient subsets for which these PARP inhibitor combinations are indicated, as subtle differences exist between these regimens and indications, according to Garje. For instance, olaparib plus abiraterone and niraparib plus abiraterone are both approved by the FDA for patients with 

-mutated mCRPC. In contrast, talazoparib plus enzalutamide is FDA approved for a broader population of patients with homologous recombination repair gene mutations. Evaluating the adverse effect profiles and potential drug-drug interactions of these regimens further aids in selecting the most suitable treatment options for individual patients, Garje says. The FDA approvals for these 3 PARP inhibitor–based combinations has improved the treatment paradigm in prostate cancer, and underscores the importance of employing genetic testing to identify patients who are eligible for each of these therapies, Garje concludes.

Rohan Garje, MD, discusses considerations when choosing between FDA-approved PARP inhibitor–based combinations for patients with mCRPC.

Rohan Garje, MD, discusses the evolving use of genomic testing and targeted treatment approaches in prostate cancer.

Dr Garje on the Use of Genomic Testing and Targeted Therapy in Prostate Cancer  

Rohan Garje, MD, chief, Genitourinary Medical Oncology, Miami Cancer Institute, Baptist Health, discusses the evolution of genomic testing and targeted treatment approaches in prostate cancer, as well as challenges associated with their implementation in clinical practice, as highlighted in his presentation at the Second Annual Miami Cancer Institute Precision Oncology Symposium.

Genomic testing has rapidly evolved in the field of prostate cancer over the past decade, driven primarily by the approvals of PARP inhibitors and other biomarker-driven therapies, Garje begins. Previously, genomic testing was not widely performed. However, the advent of targeted therapy in prostate cancer spurred a growing need for identifying biomarkers that can guide treatment selection and risk stratification for patients, Garje explains.

Although the feasibility and efficacy of biomarker-driven therapies is well established, their integration into real-world clinical practice has encountered challenges, resulting in a significant delay between regulatory approval and widespread adoption in community settings, Garje notes. Addressing this implementation gap is imperative to ensure patients benefit from timely access to precision medicine approaches, according to Garje. Efforts are underway to streamline the integration of genomic testing into routine clinical workflows, aiming to accelerate the translation of scientific advancements into improved patient care, Garje says.

One unique aspect of prostate cancer management is the use of novel prostate-specific membrane antigen (PSMA)–targeted imaging technologies, Garje continues. Advanced imaging agents enable the precise localization of cancerous lesions based on PSMA expression, providing valuable information for treatment planning, Garje explains. Leveraging these imaging data, agents such as lutetium Lu 177 vipivotide tetraxetan (Pluvicto) can selectively target PSMA-expressing prostate cancer cells, offering a personalized and effective treatment approach, Garje states.

The combination of genomic insights with image-driven identification of specific receptors represents a promising strategy to optimize treatment outcomes for patients with advanced prostate cancer, Garje emphasizes. By integrating cutting-edge technologies and therapies, clinicians can tailor treatment plans to individual patients, maximizing therapeutic efficacy and simultaneously minimizing toxicities, he explains.

Moving forward, efforts to enhance the adoption of genomic testing and innovative imaging techniques in prostate cancer care will continue to evolve, empowering clinicians to deliver targeted treatments that address patients' unique molecular characteristics, Garje concludes.

Rohan Garje, MD

Articles