Managing Prostate Cancer Surgical Patients during the COVID-19 Pandemic: A Brief Report of the Duke Cancer Institute’s Initial Experience

Moul is a urologic oncologist at the Duke Cancer Institute in Durham, NC.

Chang is a resident urologist at the Duke Cancer Institute and Duke University Medical Center in Durham, NC.

Inman is a urologist and surgical oncologist at the Duke Cancer Institute in Durham, NC.

Figure. COVID-19 data obtained online via the North Carolina Electronic Disease Surveillance System

CASE 1. High Risk: Postpone due to COVID-19; Placed on ADT

Case 2. High Risk: Postponed Due to COVID-19; Placed on ADT

Case 3. High Risk: Recommended to Proceed to RP

Case 4. High Risk: Recommended to Proceed to RP

Case 5. High Risk: Surgery postponed; Recommended to Start DT and Consider EBRT (not RP)

Case 6. Low Risk: Postpone RP up to 6 months or Consider Active Surveillance

Case 7. Intermediate Risk: Postpone RP up to 3 months

TABLE 1. Risk Groups- Five Current Groups for Localized Prostate Cancer

TABLE 2. Duke University Triage of Prostate Cancer During COVID-19 Outbreak (Version 1 April 6, 2020)

The  coronavirus disease 2019 (COVID-19) pandemic has rapidly placed tremendous stress on health systems around the world. In response, multiple health systems have postponed elective surgeries in order to conserve hospital beds and personal protective equipment, minimize patient traffic, and prevent unnecessary utilization and exposure of health care workers. The American College of Surgeons released the following statement on March 13, 2020: “Each hospital, health system and surgeon should thoughtfully review all scheduled elective procedures with a plan to minimize, postpone, or cancel electively scheduled operations, endoscopies or other invasive procedures until we have passed the predicted inflection point in the exposure graph and can be confident that our health care infrastructure can support a potentially rapid and overwhelming uptick in critical patient care needs."Within this current COVID-19 environment, we outline our approach to stratifyingsurgical management of prostate cancer here at Duke University Hospital.

Introduction

The  coronavirus disease 2019 (COVID-19) pandemic has rapidly placed tremendous stress on health systems around the world. In response, multiple health systems have postponed elective surgeries in order to conserve hospital beds and personal protective equipment, minimize patient traffic, and prevent unnecessary utilization and exposure of health care workers.¹ The American College of Surgeons released the following statement on March 13, 2020: “Each hospital, health system and surgeon should thoughtfully review all scheduled elective procedures with a plan to minimize, postpone, or cancel electively scheduled operations, endoscopies or other invasive procedures until we have passed the predicted inflection point in the exposure graph and can be confident that our health care infrastructure can support a potentially rapid and overwhelming uptick in critical patient care needs.”² In our state, North Carolina, Governor Roy Cooper requested that all hospitals postpone elective and nonurgent procedures and surgeries effective March 23, 2020.

Aside from clear-cut examples of immediately life-threatening versus truly elective cases, most procedures exist on a continuum of potential harm that may result from postponing surgical treatment. This is particularly germane to surgeries for cancer, in which long-term outcomes are often dependent on timely intervention. In urology, considerations regarding case stratification have been published to help guide our review processes.^3-5 However, ultimately, this process needs to be customized to the level of COVID-19 severity in each region. The goal is to remain vigilant and prepared for the population-level risk of COVID-19, but to reasonably ration available resources to treat non–COVID-19 diseases that threaten our patients. 

In North Carolina, testing-confirmed COVID-19 case numbers and hospital resources are illustrated in the Figure. At this point (as of April 9, 2020), case numbers in North Carolina are rising but lag behind those of the main US epicenters; hospital resources remain relatively well preserved.

Within this current COVID-19 environment, we outline our approach to stratifying surgical management of prostate cancer here at Duke University Hospital. 

Prostate Cancer 

The diagnosis and management of adenocarcinoma of the prostate, or prostate cancer (PC), have been and remain controversial during the best of times, but the COVID-19 pandemic certainly adds fuel to the fire. Providing safe and appropriate care requires a nuanced approach. Fortunately, risk stratification of the severity of localized and advanced PC has been in practice for many years and is being used now to its full extent to triage prostate cancer patients for surgical care. 

Traditionally, PC had been placed into 3 risk groups as defined by D’Amico et al: low, intermediate, and high risk. These were later adopted by major professional organizations, including the American Urological Association, National Comprehensive Cancer Network, and American Society of Clinical Oncology.^6-9 These organizations have relied on American Joint Committee for Cancer for the backbone stage groups¹⁰ In 2020, most experts use a classification of 5 risk groups for localized prostate cancer (Table 1). The boxed areas are the two highest categories of high and very high risk disease.  Men in these two groups at our center have been considered to move forward with scheduled surgery during the COVID-19 pandemic subject to local hospital considerations regarding the severity of COVID and would be the first patients to be rescheduled for surgery once the COVID pandemic subsides. In our risk schema, we have reverted to the traditional 3 risk group system collapsing very low and low risk and combining high and very high risk.

The staffs of the Duke Cancer Institute Center for Prostate and Urologic Cancers, working with the Duke Cancer Center’s surgeon-in-chief and his office, developed a COVID-19 triage table (Table 2) to help our teams make prudent and consistent decisions about prostate cancer surgeries during the pandemic surge for as long as local conditions dictate. This schema also stratifies patients for clinic visits and procedures. Currently, our timelines for care are:

• Priority 3: See/do now

• Priority 2: Delay 6-12 weeks

• Priority 1: Delay 3-6 months

Importantly, when this is communicated to patients, it must be made clear that these timelines are approximate and likely will change. If COVID-19 worsens, the timelines will shift to incorporate significantly longer delays.

To further illustrate the process for triage of localized prostate cancer at our center, we offer several specific surgery case examples. With these, we hope to help practicing urologic oncologists to make triage and treatment recommendations for their patients. 

Judd Moul, MD, FACS harnesses his prior military experience and uses this knowledge in concert with his colleagues at Duke to provide risk stratification in order to triage the care of men with prostate cancer during this current pandemic. As he points out the treatment of all stages of prostate cancer, particularly early prostate cancer remains controversial. The current challenges and limitations of care posed by the COVID-19 pandemic has further highlighted these controversies.

I applaud Moul and his associates for educating us in this very difficult time.

REFERENCES

Cases

Case 1 involves a high-risk 62-year-old African American man with a prostate-specific antigen (PSA) measurement higher than 20. We contemplated moving forward with his case but instead decided to postpone surgery and start androgen deprivation therapy (ADT) with leuprolide at a 45-mg 6-month depot dose. This decision was due to several factors, including his very large prostate gland (measuring more than 100 cc), the possibility of a narrow pelvis due to his ethnicity, and prior pelvic surgery. We surmised that his case, as treated at our center, could be more difficult as compared with an average overnight admission for open or robotic radical prostatectomy (RP), with potentially more bleeding and more use of health care resources. Based on the literature about the use of neoadjuvant ADT, we felt that this course of action would have a low probability of harm and would also decrease his prostate size, making future surgery potentially less morbid. Based on work from Gleave et al in a Canadian randomized controlled trial, we will continue the ADT for at least 3 months and reevaluate him for RP at that time.¹¹ 

Under normal conditions, we generally do not administer neoadjuvant ADT to RP patients because of the lack of a proven survival benefit.^12,13 However, during COVID-19, we are trying to alleviate harm from delaying surgery, and prior trials did show that taking the time to prescribe hormonal therapy did not lessen survival versus proceeding directly to surgery.

Case 2. Here, an African American male aged 64 years has high-volume grade group 2 and 3 PC, a PSA of 44, and clinical stage T2a disease. As such, he is classified as high risk. We elected to postpone his surgery in part because he also has uncontrolled diabetes, and we had concern that proceeding to RP during this pandemic could have led to excess hospitalization and use of excess health care resources. We also elected to start neoadjuvant ADT, a more controversial decision in this case because the hormonal therapy could make diabetes control more challenging. In the end, however, we felt that the high-volume cancer should be controlled without delay; we also took into consideration that the patient might ultimately favor radiation over surgery. Some experts could argue that we should postpone this case for only 30 days and hold off on use of ADT. However, the current uncertainty of the COVID-19 peak and the potential need to use excess health care resources in the perioperative period for this patient prompted us to make the case management decisions described above.

Case 3. This case involves a very healthy African American man, aged 61 years, with Gleason 4+4=8 in only 2 cores but with a PSA higher than 30. Because he was in excellent health and had high-risk disease, he was deemed appropriate for surgery based on day-to-day conditions at our center. He was negative for COVID-19 based on a test performed 72 hours before surgery at our drive-through testing site. (As of early April 2020, our health system requires preoperative COVID-19 testing for all scheduled surgery patients, performed at our center; we currently do not allow testing outside of our own health system.) 

To not overutilize health care resources, we performed only a unilateral right-side pelvic lymphadenectomy in association with the radical retropubic prostatectomy; we did not perform an extended lymph node dissection. Our reasoning was that we did not want to risk a lymphocele that would possibly increase utilization of health care resources during our upcoming COVID-19 peak. 

Our enhanced recovery after surgery protocol for RP dictates the use of bupivacaine liposome injectable suspension (Exparel 266 mg/20 cc mixed with 20 cc 0.25% standard bupivacaine) in the incision on closure and use of enoxaparin sodium (Lovenox 0.4 ml/40 mg subcutaneous, daily). The upivacaine increases the probability of discharge from the hospital on postoperative day 1, which is always desirable but is even more so during the COVID-19 pandemic. The enoxaparin is for deep venous thrombosis prophylaxis, but this might also increase the risk of a lymphocele. This was our reasoning for the unilateral standard lymphadenectomy.

Case 4. This healthy 58-year-old healthy Caucasian man with lower volume Gleason 8 prostate cancer but with a PSA level of over 20.  This gentleman is a commercial pilot and was originally contacted and asked to postpone his surgery and initiate short term ADT (this was very early in our hospital preparedness where any surgery was being subject to postponement).  The patient was, understandably, not keen for preoperative ADT and was concerned that use of ADT may lengthen his return to flight status with the Federal Aviation Administration (FAA).  Ultimately, he was deemed high risk and was approved to move forward with radical retropubic prostatectomy and unilateral pelvic lymphadenectomy after negative COVID-19 testing.

Case 5. This Caucasian male business executive, aged 75 years, was recommended by his community urologist to undergo external beam radiotherapy and neoadjuvant hormonal therapy due to his age and morbid obesity (body mass index = 38). However, the patient was keen to have surgery instead and presented to our center for a second opinion soon before COVID-19 arrived in our area. He was scheduled for radical retropubic prostatectomy but was very strongly encouraged to see a radiation oncologist for proper multidisciplinary education and counseling. When the COVID-19 crisis emerged, he and his local urologist were contacted by our team with our recommendation that he start leuprolide neoadjuvant hormonal therapy and then strongly consider external beam radiotherapy and not proceed to RP. The patient refused and is currently on the surgical schedule for fall 2020. This case illustrates that, even in a pandemic, we cannot force therapy decisions on patients. As of now (early April 2020), it remains unclear what management this patient will ultimately elect.

Case 6. Prior to the pandemic, this individual with male hypogonadism and obesity, aged 62 years, was diagnosed with low-risk localized prostate cancer. He initially elected RP because he has low testosterone which, arguably, might lessen the long-term success of active surveillance and increase his risk for recurrence and unfavorable pathology. Under normal circumstances, low-risk men are asked to choose between active treatment and active surveillance, and this patient chose surgery. When COVID-19 worsened in our region and our COVID-19 surgical guidelines were announced, we contacted him to say that his surgery could be postponed up to 6 months. At that point, he agreed to active surveillance. He will have a follow-up PSA measurement and prostate examination 6 months after his biopsy date, and he may ultimately have a prostate MRI and/or repeat prostate biopsy before being reconsidered for surgery. Low-risk men, most of whom should probably be placed on active surveillance anyway, are “low-hanging fruit” during COVID-19, those in whom surgery can be postponed or avoided to help prevent overburdening the health care system during the surge. 

Case 7. A healthy Caucasian man, aged 70 years, presented to our center with Gleason 8 in 4 of 12 cores, a PSA of 7.5, and clinical stage T1c disease. He had been scheduled for RP, with a surgery date several weeks out. This date proved to coincide with the start of the COVID-19 pandemic in our area. At the time of the COVID-19 surgery postponement process for this patient, we realized that a pathology review had not yet been completed in accordance with our policy of having outside pathology slides reviewed at our center for accuracy. Interestingly, after the pathology review, the patient was downgraded to Gleason 3 + 4 = 7 in the 4 involved cores, reclassifying his risk group from high to intermediate; surgery was postponed for up to 3 months. Before the pathology review, the patient had been offered neoadjuvant ADT but declined. In retrospect, in light of the subsequent pathology downgrading, this was a wise move.

Summary

The COVID-19 pandemic scenario continues to change and vary throughout the United States and the world. Our process at Duke will undoubtedly evolve. Nevertheless, we wanted to share our initial experience with COVID-19 surgical triage with some specific examples.

Overall, healthy men with high- and very high-risk localized prostate cancer are currently proceeding to surgery, while low- and intermediate-risk men are being postponed. We have also elected to employ neoadjuvant ADT selectively in less-healthy men who may require more health care resources at a critical time when our health system is at or nearing peak COVID-19 capacity.

For additional commentary and perspective from Eric A. Klein, MD of the Glickman Urological & Kidney Institute at the Cleveland Clinic, visit http://cancernetwork.com/klein_perspective

Disclosures:

Financial Disclosure: The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

REFERENCES

1. Brindle M, Gawande A. Managing COVID-19 in surgical systems. Ann Surg. Published online March 23, 2020. doi:10.1097/SLA.0000000000003923

2. COVID-19: recommendations for management of elective surgical procedures. American College of Surgeons. Published March 13, 2020. Accessed April 9, 2020. https://www.facs.org/covid-19/clinical-guidance/elective-surgery

3. Ficarra V, Novara G, Abrate A, et al; Members of the Research Urology Network (RUN). Urology practice during COVID-19 pandemic. Minerva Urol Nefrol. Published online March 23, 2020. doi:10.23736/S0393-2249.20.03846-1

4. Goldman HB, Haber GP. Recommendations for tiered stratification of urologic surgery urgency in the COVID-19 era. J Urol. Published online April 21, 2020. doi:10.1097/JU.0000000000001067

5. Stensland KD, Morgan TM, Moinzadeh A, et al. Considerations in the triage of urologic surgeries during the COVID-19 pandemic. Eur Urol. Published online April 9, 2020. doi:10.1016/j.eururo.2020.03.027

6. Bekelman JE, Rumble RB, Chen RC, et al. Clinically localized prostate cancer: ASCO clinical practice guideline endorsement of an American Urological Association/American Society for Radiation Oncology/Society of Urologic Oncology guideline. J Clin Oncol. Published online September 5, 2018.  doi:10.1200/JCO.1800606

7. Carter HB. American Urological Association (AUA) guideline on prostate cancer detection: process and rationale. BJU Int. 2013;112(5):543-547. doi:10.1111/bhu.12318

8. D’Amico AV, Moul J, Carroll PR, Sun L, Lubeck D, Chen MH. Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. J Clin Oncol. 2003;21(11):2163-2172. doi:10.1200/JCO.2003.01.075

9. Mohler JL, Antonarakis ES. NCCN Guidelines updates: management of prostate cancer. J Natl Compr Canc Netw. 2019;17(5.5):583-586. doi:10.6004/jnccn.2019.5011

10. Buyyounouski MK, Choyke PL, McKenney JK, et al. Prostate cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA: Cancer J Clin. 2017;67(3):245-253. doi:10.3322/caac.21391

11. Gleave ME, Goldenberg SL, Chin JL, et al; Canadian Uro-Oncology Group. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol. 2001;166(2):500-506; discussion 506-507.

12. Fair WR, Cookson MS, Stroumbakis N, et al. The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results. Urology. 1997;49(3A suppl):46-55. doi:10.1016/s0090-4295(97)00169-6

13. Klotz LH, Goldenberg SL, Jewett M, et al. CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology Group. Urology. 1999;53(4):757-763. doi:10.1016/s0090-4295(98)00616-5