Referral Patterns and Treatment Preferences in Patients With Advanced Prostate Cancer: Differences Between Medical Oncologists and Urologists

Managing prostate cancer typically requires a multidisciplinary team approach, and many patients with prostate cancer consult with both a urologist and an oncologist along their continuum of care. Historically, urologists have treated patients with prostate cancer in the early stages of their disease and then transferred care to an oncologist when the cancer recurred, metastasized, became more aggressive, or required chemotherapy.¹ The optimal treatment strategy for patients with prostate cancer and when the transfer of care from urologists to oncologists occurs are disputed.² Previous studies have compared the differences in treatment patterns, health care resource utilization, cost, and toxicity of patients with prostate cancer receiving treatment from oncologists urologists. Results from a US study suggest that patients treated by oncologists had higher percentages of inpatient stays, emergency room use, ambulatory visits, and higher costs.³ Additionally, results from a Canadian study showed that patients treated by oncologists had a higher percentage of hospital visits overall and for treatment-related toxicity for patients with metastatic castration-resistant prostate cancer (mCRPC).⁴ However, these reports have limitations, including a selection bias with oncologists caring for patients with more advanced disease and the use of cytotoxic therapy with its associated adverse events.

Between 2004 and 2020, the US Food and Drug Administration approved eight new agents for the treatment of prostate cancer, including four androgen-signaling–targeted inhibitors that impair androgen-receptor function (the androgen synthesis inhibitor, abiraterone acetate and the androgen receptor antagonists: enzalutamide, apalutamide, and darolutamide), two taxane-based chemotherapeutic agents (docetaxel and cabazitaxel), one bone-targeted alpha-emitting radiopharmaceutical agent (radium-223), and one autologous cell-based immunotherapy (sipuleucel-T). The historical treatment paradigm was to first use a luteinizing hormone-releasing hormone  analogue as androgen deprivation therapy (ADT) with or without an antiandrogen agent, then to use chemotherapy agents sequentially (docetaxel and cabazitaxel) upon the development of castration resistance, and finally to use either abiraterone acetate or enzalutamide for castration-resistant disease. However, a recent spate of well-conducted phase 3 clinical trials challenged this paradigm, leading to current guideline recommendations for the use of either docetaxel, apalutamide, enzalutamide, or abiraterone acetate in addition to ADT in metastatic castration-naïve prostate cancer.^5-10 For oligometastatic disease, external beam-radiation therapy to the prostate bed when added to ADT also has demonstrated improved outcomes and was addressed within the larger STAMPEDE trial.¹¹ Additionally, recent prospective randomized trials have demonstrated the efficacy of the antiandrogen receptor antagonists, including the use of enzalutamide, darolutamide, or enzalutamide for in nonmetastatic CRPC (M0CRPC).^12-14 For CRPC with metastatic disease, current guidelines support the use of all the above agents, as well as sipuleucel-T and radium-223, for certain scenarios for mCRPC.¹⁵ These multiple options have revolutionized the care of patients with advanced CRPC; it is likely that such patients have received several classes of drugs including chemotherapy for either castrate-naïve disease and/or for M0CRPC. These changes in therapy can impact referral patterns, such as the early introduction of chemotherapy, which challenges the historic pattern of referral to the medical oncologist only after castrate resistance. This also could create a scenario where urologists are able to treat patients with advanced CRPC with various noncytotoxic options.

There has been a significant uptake in the utilization and delivery of noncytotoxic therapies among urologists in the past 5 years, particularly in patients with mCRPC. Urologists are now involved not only in the management of early-stage patients, but they also are play an increasingly significant role in the management of mCRPC.^1,16,17 In addition to the easy-to-use, newer, noncytotoxic therapies for advanced prostate cancer, there has been an expansion of services within urology practices (such as integrating radiation therapy, radiopharmaceuticals, and immunotherapy) allowing urologists to play a larger role in the management of patients with advanced prostate cancer.^16,18,19

While academic cancer centers and multispecialty groups (wherein medical oncologists, radiation oncologists, and urologists form a part of, or are employed by, a single health care system) typically have a multidisciplinary care plan for men with prostate cancer, little is known about these care patterns in the community setting when care is rendered by providers representing discreet specialty practices. In this descriptive study, we sought to assess the differences between medical oncologists and urologists regarding referral patterns and basic treatment decisions in men with advanced prostate cancer in the community setting.

US-based community health care providers of diverse practice types were invited to attend virtual meetings in August 2020 with the goal of collecting information on treatment decision-making in various clinical scenarios, as well as addressing various practice-based challenges and initiatives. The participants were compensated for their time based on fair market value. The eligibility criteria for physicians to participate in these programs included being a medical oncologist or urologist, practicing in a community-or hospital-based setting in the United States, and having experience treating prostate cancer.

A web-based, premeeting survey was fielded to the participants, and completion was required to attend the meeting. Survey questions were fielded during the virtual meetings and participants’ responses were captured using an audience response system (ARS). Each participant was allowed a fixed time to submit their responses following each question. The participants were encouraged, but not required, to respond to every ARS question. In addition to questions regarding demographics, practice characteristics, and typical referral patterns, the participants were presented with two hypothetical patient cases of men with mCRPC: one with asymptomatic progression and one with symptomatic skeletal metastases. Identical treatment options were provided, and the preferred treatment responses were collected. All responses are summarized using descriptive statistics.

A total of 66 oncologists and 69 urologists from various regions in the United States participated in this research. The participants were mostly community-based physicians: 76% of oncologists and 89% of urologists are in private community practices. Of the oncologists and urologists, 27% and 51% have been in practice for more than 20 years, and 50% and 81% see an average of more than 20 patients per day, respectively (Table 1). 

Among the urologists, 75% estimated that they refer ≤25% of all of their patients with prostate cancer to oncologists. On the other hand, 70% of oncologists reported that more than 50% of their patients with prostate cancer are referrals from urologists (Figure 1). Other referring physicians identified included primary care physicians (76%), radiation oncologists (46%), and hospitalists (40%). Most urologists perceive oncologists as comanagers (86%) for their patients with prostate cancer, and they rarely (9%) transfer the care of their patients completely to oncologists. 

The need for chemotherapy (52%) or disease progression to mCRPC (22%) drives referrals from urologists to oncologists (Table 2). Oncologists reported that upon referral, their patients with prostate cancer have already been exposed to hormone therapy (75%), radiation therapy (66%), and/or surgery (43%) (Table 3).

For second-line treatment of asymptomatic patients with mCRPC, oncologists most commonly prescribe hormone therapy (60%) and chemotherapy (23%), while urologists most commonly prescribe sipuleucel-T (45%) and hormone therapy (38%) (Figure 2). For second-line treatment of patients with mCRPC and symptomatic bony disease, oncologists most commonly prescribe chemotherapy (44%) and radium-223 (34%), while urologists most commonly prescribe radium-223 (47%) and hormone therapy (22%) (Figure 3). 

In our cohort of physicians surveyed, a minority of urologists refer their patients to medical oncologists. The urologists typically only refer their patients when cytotoxic therapy is required, and the vast majority retain comanagement of the patient with the medical oncologist. On the other hand, most patients with prostate cancer referred to the medical oncologists are referred by urologists. These findings imply that urologists, as a group, are more involved in treatment decision-making and provide care to a larger proportion of men with prostate cancer, as well as retain their role in such care for a greater portion of the patient journey, even when surgical treatment is not a treatment option. As more oral or non-cytotoxic therapies for prostate cancer come to market, it can be expected that the role of urologists will extend further in the care continuum. With the advent of radiopharmaceutical agents that may have greater efficacy in the relapsed mCRPC state beyond cytotoxic therapy, the balance of treatment in mCRPC may further shift toward urologists.²⁰ Overall, there appears to be a change in urology from a primary practice to a focus on office and nonsurgical practice. Given their greater role in management of advanced disease, urologists need adequate education and resources to care for the patient with advanced cancer including management of cancer associated syndromes such as cachexia, pain, metabolic abnormalities such as hypercalcemia of malignancy, and timely integration of supportive and palliative care. Further, urologists should be engaged in the biopharmaceutical drug development process, including as investigators in clinical trials for new treatments. Greater education regarding new therapies and appropriate sequencing strategies should also be directed toward urologists. In addition, patients and caregivers, as well as primary care providers, should be educated on an appropriate referral process with newly diagnosed prostate cancer.

However, the impact of the type of primary provider on cancer outcomes in men with prostate cancer has not been studied including survival, toxicity, health-related quality of life, and the overall cost of care. It is not certain if patients with poor performance status and high comorbid disease burden are more likely to be referred to medical oncologists for management; such patients have predictably higher cost of cancer care.²¹ There are plethora of treatment choices with strong levels of evidence to support each agent, as well as inclusion of these agents in national treatment guidelines, which provides justification for providers to choose their preferred agents and a preferred sequence of therapies. The differences in outcomes between multiple agents within the same class have not been well-studied. Thus, there is a great unmet need in establishing the appropriate treatment paradigm with the best efficacy and least safety toxicity to the patient. Ideally, such a pathway should be followed by all providers in advanced disease management, irrespective of their specialty of practice. Further, the financial toxicity of various therapies upon the patient needs to be considered, especially if efficacy and toxicity between agents are comparable.²²

Our study was limeted by its modest sample size of the providers, the use of recall to answer questions posed, and the limited depth to the questions given as inherent to the ARS technology. Despite these limitations, our work can inform comparative effectiveness research to study efficacy, toxicity, and financial burden, as well as the impact of the primary provider upon outcomes in men with advanced prostate cancer.

Urologists prefer to treat with nonchemotherapy options when possible and retain oncologic care for most of the patients’ cancer journeys. However, urologists refer patients with advanced prostate cancer to oncologists for chemotherapy when needed, and this is a major reason for referral from urologists to oncologists. The impact of these provider preferences upon patient outcomes in the real world and impact of newer modalities such as nuclear theranostics upon these patterns needs further research.

Authors: Ajeet Gajra, MD, FACP¹; Skyler Hime Rupard, MS¹; Yolaine Jeune-Smith, PhD¹; Bruce Feinberg, DO¹

Affiliations:¹Cardinal Health Specialty Solutions, Dublin, OH

Disclosures: The authors have no disclosures to report.

Address correspondence to:
Ajeet Gajra
(847) 887-2391
ajeet.gajra@cardinalhealth.com