In addition to the impact of the infection, collateral effects such as restricted healthcare access and service provision must also be taken into consideration. In the present study, we observed that the percentage of patients with more advanced stage cancers among newly diagnosed NSCLC patients during the pandemic was higher than that of previous years.
During the influenza H1N1 epidemic in 2009, a higher incidence of pneumonia and higher mortality were reported among patients with cancer, compared with that observed with the general population [13]. Nevertheless, there is a lack of studies examining the diagnosis of lung cancer and treatment guidelines during an epidemic. During the COVID-19 pandemic, several international societies presented guidelines for cancer diagnosis and treatments based on expert opinions [14]. However, these guidelines are not yet evidence-based. As there is still no effective drug or vaccine for COVID-19, it is difficult to anticipate when the pandemic will be eradicated. Meticulous evidence-based preparation is needed as another novel infectious disease may occur in the future [15].
The collateral effects of COVID-19 pandemic on the healthcare system affected both healthcare providers and patients. With a growing number of COVID-19 patients requiring hospitalization, the reallocation of human and other resources is a common phenomenon among healthcare facilities [16]. Consequently, clinical activities needed to diagnose and treat diseases, including cancer, will be hindered. In our study’s hospitals, personnel in the general cancer diagnosis areas were relocated to address the staff shortage for COVID-19 screening and care. A report on the impact of COVID-19 on the diagnosis of cancer showed that registration of new patients with cancer in the Netherlands national cancer registry dropped by about 25% between March and May 2020 [17]. In the United Kingdom, referrals of cancer-suspected cases decreased by about 80% [18, 19]. Patients are reluctant to visit a healthcare facility out of fear for infection. A survey on patients with lung cancer who participated in a clinical trial in Taiwan during the SARS outbreak reported that about 64% of the patients were reluctant to visit a hospital out of fear for infection, and about 4% of the patients decided to discontinue all treatment due to concerns of infection [20]. In fact, the decline in healthcare utilization may be only natural following media reports and study findings confirming local outbreaks of COVID-19 in healthcare facilities [21].
However, there is a problem that excessive concerns regarding COVID-19 beyond what is necessary could worsen the avoidance of healthcare facilities among patients with cancer and delay the necessary medical diagnosis and treatment. In the present study, the increased percentage of patients with stage III or IV cancer with a decreased percentage of patients with earlier stages of cancer in the NSCLC group suggested a presentational delay in the diagnosis of lung cancer. Patients in symptomatic stage I or II lung cancer may have been diagnosed at an advanced stage after disease progression due to presentational delay. In contrast, asymptomatic early-stage patients are mostly diagnosed through screening; it is postulated that the number of early diagnoses of lung cancer decreased due to a decline in the medical checkup rate. The longer the pandemic period, the more significant the impact can be expected. On the other hand, the percentage of patients with limited stage cancer increased, albeit statistically insignificant, in the SCLC group. Because symptom onset is more common with SCLC than with NSCLC, this result may be attributed to the possibility that these patients consulted at a healthcare facility early on owing to respiratory symptoms during the COVID-19 pandemic [22].
The COVID-19 pandemic also impacted the treatment process. Anticancer therapy or surgery was postponed or canceled. A modeling study that analyzed the impact of delayed cancer surgery due to the COVID-19 pandemic reported that a three-month and six-month delay of surgery decreased the anticipated life-years gain after surgery by 19 and 43%, respectively [23]. Moreover, the impact was greater among patients with lung cancer. A dilemma occurs when elective surgeries are postponed in adherence to physical distancing and reorganization of healthcare resources because it contradicts the goal of minimizing delays of curative surgeries. Likewise, when considering cytotoxic anticancer therapy, it is important to weight its benefits with the risk of infection due to immunosuppression. For advanced stage lung cancer, it is ideal to choose agents that could reduce inpatient hospitalization or outpatient clinic visits when choosing cytotoxic anticancer agents for palliative therapy. The clinical and radiological features of COVID-19 pneumonia may be difficult to differentiate from pneumonia during anticancer therapy or the pneumonitis during immunotherapy or targeted therapy [24]. As such, the threshold for COVID-19 screening should be lowered for patients with lung cancer currently undergoing treatment. Healthcare providers should consider prompt testing of these patients for COVID-19 based on their symptoms and radiologic findings even when they had no prior contact with a confirmed patient.
The mortality from SARS-COV-2 infection is higher among patients with cancer than in the general population. In a cohort study of 928 cancer patients confirmed with COVID-19 infection in the US, Canada, and Spain, the all-cause mortality rate was high at 13% [25]. Factors associated with mortality risk were age, male sex, number of comorbidities, poor performance status, smoking status, and active cancer status. However, history of surgery within 4 weeks and overall anticancer treatment status, including targeted therapy, cytotoxic therapy, and immunotherapy, were not associated with mortality risk. A study on 102 lung cancer patients diagnosed with COVID-19 also demonstrated that the severity and mortality of COVID-19 were related to patient-specific features (smoking, chronic obstructive pulmonary disease, and heart failure) rather than cancer-specific features (surgery and recent systemic treatments) [26]. Therefore, if COVID-19 is well contained within the hospital, and healthcare resources are utilized appropriately, hospitals should avoid delaying surgery of operable cancers except typical indolent cases even during a pandemic.
Our research has limitations. First, this study included a limited number of hospitals and patients. Second, long-term follow-up is required to evaluate the prognosis of patients with a delayed diagnosis of lung cancer. Some patients with slowly progressing lung cancer may be safe with late diagnosis. However, most patients progress rapidly, even with early lung cancer [27, 28]. Considering the study results in which the median overall survival was 9 months when not treated at stage I lung cancer, it is reasonable to evaluate the rapid stage shift during the five-month study period [29]. Third, the effects of SARS-CoV-2 infection on the diagnosis and treatment process of lung cancer were not evaluated. None of the newly diagnosed lung cancer patients included in this study was diagnosed with COVID-19.