Currently, there is a global pandemic surrounding the spread of betacoronavirus SARS-CoV-2 leading to Coronavirus Disease 2019 (COVID-19). The rapid spread to all corners of the globe has had tremendous health and economic implications, including the appropriate allocation of healthcare resources. Considering that hospitals may be overwhelmed quickly given the need for a proportion of patients that require hospitalization with possible ventilator support, there is a necessity to decrease the use of items essential for the care of patients with COVID-19 including ICU beds, ventilators, personal protective equipment, and terminal cleaning supplies. This includes reassessing the priority and implications of treatments, including prostate cancer screening.
Screening for malignancies refers to the use of a diagnostic test in a population without evidence of the disease, which is performed based on the assumption that detection and treatment of the disease before clinical manifestation will improve treatment outcomes. Prostate cancer is a condition for which screening is both valuable and feasible based on the World Health Organization’s conditions that (i) the malignancy in question represents an important health problem, (ii) there should be a recognizable early or latent phase of the disease, (iii) the natural history of the disease should be well understood, and (iv) there should be accepted treatment options for the disease after it is diagnosed.1
Other articles in the UroToday Center of Excellence Library of Resources have covered in-depth the implications of prostate cancer screening, as well as recommendations for treatment of localized prostate cancer during the COVID-19 pandemic. In quick response to the need for guideline-specific direction during these unprecedented times, the National Comprehensive Cancer Network (NCCN) has established new prostate cancer recommendations to follow during COVID-19, including the recently published “Recommendations for Prostate Cancer Early Detection During the COVID-19 Pandemic” on April 1, 2020. This article will summarize and contextualize these recommendations.
First and foremost, the NCCN recommendation acknowledges basic concepts that we as a society should adhere to, namely: patient and occupational safety, resource utilization stewardship, and maintaining social distancing. Considering the ease of spread through asymptomatic carries of SARS-CoV-2, minimizing patient and health care provider exposure is crucial for patient and occupational safety. In an effort to minimize exposure, it is paramount to practice social distancing (at least six feet apart) in order to minimize contact between individuals and the health care system. Furthermore, much like in non-pandemic times, the NCCN endorses the principles of shared-decision making,2 recognizing the unique needs of every patient.
Regarding prostate-specific antigen (PSA) screening, the most recent NCCN guidelines were updated on May 31, 2019 (Version 2.2019).3 The guideline provides guidance regarding how to perform screening among men who opt for participation in a PSA-based prostate cancer screening program after appropriate discussion regarding its risks and benefits. The NCCN recommends starting screening at age 45 with variable screening intervals on the basis of the initial PSA result. For men 45-75 years of age, the following algorithm is proposed following the baseline PSA:
- If the PSA is <1 ng/mL and the digital rectal exam (DRE) (if done) is normal, then repeat PSA testing should be repeated at two- to four-year intervals
- If the PSA is 1-3 ng/mL and the DRE (if done) is normal, then repeat PSA testing should be repeated at one- to two-year year intervals
- If the PSA is >3 ng/mL and/or the DRE is very suspicious, then the patient should be considered for a biopsy +/- additional biomarker +/- a multiparametric MRI
For men >75 years of age and the patient is very healthy with little to no comorbidities, the following algorithm is proposed following the baseline PSA:
- If the PSA is <4 ng/mL and the DRE (if done) is normal and there are no other indications for a biopsy, then repeat testing should be performed at one- to four-year intervals in select patients
- If the PSA is ≥4 ng/mL or the DRE is very suspicious, then the patient should be considered for a biopsy +/- additional biomarker +/- a multiparametric MRI
Although this is a sophisticated algorithm to follow during non-pandemic times, the NCCN in their COVID-19 pandemic update strongly recommends avoiding routine prostate cancer screening, including a PSA and DRE, for all asymptomatic men until the pandemic is over.
For patients that have an elevated PSA and/or abnormal DRE, these patients should defer further testing (including additional laboratory testing, imaging, and prostate biopsy), until healthcare facilities are considered safe and have a low risk of COVID-19 infection. Although there is a paucity of literature assessing the impact of delaying a biopsy in the setting of an elevated PSA and/or abnormal DRE, Reading et al.4 assessed racial and ethnic variations in time to prostate biopsy after an elevated PSA, defined in this study as ≥2.5 ng/mL. These authors identified 59,506 men in the Kaiser Permanente of Southern California system that had at least one elevated screening PSA between 1998 and 2007, which comprised the cohort. Overall, the median time from elevated PSA until biopsy was 214 days, with 41% of men receiving a prostate biopsy within the study period. They found that on adjusted analysis, non-Hispanic Asian or Pacific Islander men (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.04-1.15) and non-Hispanic black men (HR 1.04, 95% CI 1.00-1.08) had a shorter time to prostate biopsy after an elevated screening PSA compared to the non-Hispanic whites. Although this study did not look at the risk of worse disease based on biopsy delay, the median time of more than six months for all men in this cohort between elevated PSA and prostate biopsy fits with the NCCN’s narrative of deferring all prostate biopsies until after the COVID-19 pandemic.
The NCCN does acknowledge that there may be rare and exceptional circumstances under which a prostate biopsy is necessary for the diagnosis of a potentially lethal prostate, which may be based on PSA levels, patient symptoms, DRE findings, and/or imaging. In these instances when a more immediate biopsy is necessary rather than deferring till later, a biopsy may be considered. However, the NCCN recommends that strategies should be put in place to minimize the risk of infectious complications. These should include a thorough history to identify high-risk patients for infection, the application of local antibiograms, antibiotic augmentation, a rectal culture, and a transperineal biopsy approach. Although the transperineal approach is associated with lower risks of infectious complications compared to a transrectal approach,5 a transperineal biopsy is more painful and is typically performed in the operating room under general anesthesia. Given the need for minimizing operating room resources, personal protective equipment, and staff exposure, perhaps a transperineal biopsy is less than ideal during the COVID-19 pandemic.
As follows are several risk factors for infectious complications post-biopsy that should assist in identifying high-risk individuals:6
- Medical – diabetes, significant comorbidities (ie. Charlson Score >1), and immunosuppression (ie. steroids, chemotherapy, HIV)
- Urologic history – recent urinary tract infection or prostatitis, previous prostate biopsy infection, and a greater cumulative number of prostate biopsies
- Exposure to antibiotic resistance – antibiotics in the last six months, recent international travel (ie. to endemic resistant locations such as India or Southeast Asia, or the use of antibiotics for traveler’s diarrhea prevention), health care workers
- Colonization with resistant bacteria – colonized with fluoroquinolone-resistant E. coli via rectal culture
The NCCN recommendation highlights that the risk of a delay in diagnosis of up to six to 12 months is minimal for most prostate cancers. It is well-established that active surveillance protocols for low and very low-risk prostate cancer follow patients typically on a six-month schedule (with PSA, MRI imaging, biopsies, etc).7 Klotz et al.8 reported outcomes of 993 men with low- or intermediate-risk prostate cancer who were managed with active surveillance. With a median follow-up of 6.4 years (range 0.2 years to 19.8 years), 149 (15%) patients died. Of the 149 patients who died, only 15 (1.5%) deaths were due to prostate cancer. Thus, actuarial cause-specific survival is 98.1% at 10 years and 94.3% at 15 years. Overall, 267 (27%) of the 993 patients who began an active surveillance strategy converted to active treatment. As a result, at 15 years, 55% of men remained on active surveillance without treatment. Thus, a delay in the diagnosis of low-risk prostate cancer has no impact on downstream prostate cancer outcomes.
There is also literature to support that a delay in diagnosis of intermediate and high-risk disease does not affect outcomes. In a study of 2,653 patients that underwent radical prostatectomy, Fossati et al.9 assessed the impact of time from diagnosis to radical prostatectomy. At a median follow-up of 56 months (IQR 26-92), 283 patients experienced biochemical recurrence and 84 patients developed clinical recurrence. The median time from prostate cancer diagnosis to surgery was 2.8 months (IQR 1.6-4.7) months. The authors used nonparametric curve fitting methods to conclude that a significantly increased risk of biochemical recurrence and clinical recurrence occurred after an ~18-month delay in treatment. Even with high-risk patients, this data suggests that a 12-month delay was feasible without increasing risk of biochemical or clinical recurrence. Additionally, it took 22 years of follow-up in the Prostate Cancer Intervention Versus Observation Trial to demonstrate a statistically significant survival benefit to radical prostatectomy over observation.10
Caring for COVID-19 patients requires massive resources, requiring us as health care providers to be leaders of thoughtful, community-focused preservation of these scarce resources. Ultimately, there needs to a be balance between patient-focused with community-focused care during the COVID-19 pandemic. For this community-based perspective, we can draw from the first-hand experience of managing patients in Bergamo, Italy.11 Western health care systems revolve around the concept of patient-centered care, but as the physicians in Bergamo point out, a pandemic requires a change in perspective to a concept of community-centered care. Rather than relying heavily on the patient-physician framework, this requires experts in public health and epidemics to guide and adopt special measures to reduce epidemiologically negative behaviors. Moreover, pandemic solutions are required for the entire population and not just for hospitals. As such, prostate cancer screening and early detection during a pandemic are less important in a community-focused care model.
Finally, the NCCN recommends that health care providers should follow guidance from federal, state, and local governments, as well as leadership within individual healthcare systems. From a surgical perspective, in mid-March, the American College of Surgeons and Surgeon General recommended that health systems, hospitals, and surgeons attempt to minimize, postpone, or outright cancel electively scheduled operations. Subsequently, the American College of Surgeons provided further guidance on the triage of non-emergent surgeries, including an aggregate assessment of the risk incurred from surgical delays of six to eight weeks or more as compared to the risk of proceeding with the operation. As during non-pandemic times, principles of shared decision making when it comes to PSA testing for prostate cancer should continue, with the goal of recognizing and meeting the unique needs of each patient. As we as a community have become accustomed to during the COVID-19 pandemic, the NCCN expects these recommendations to possibly change in the midst of the current dynamic health care environment.
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Atlanta, Georgia; Christopher J.D. Wallis, MD, PhD, Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee
Published Date: April 20th, 2020