Evaluation of Watchful Waiting and Tumor Behavior in Patients With Basal Cell Carcinoma: An Observational Cohort Study of 280 Basal Cell Carcinomas in 89 Patients

Abstract

Importance: Few studies have examined watchful waiting (WW) in patients with basal cell carcinoma (BCC), although this approach might be suitable in patients who might not live long enough to benefit from treatment.

Objective: To evaluate reasons for WW and to document the natural course of BCC in patients who chose WW and reasons to initiate later treatment.

Design, setting, and participants: An observational cohort study was performed at a single institution between January 2018 and November 2020 studying patients with 1 or more untreated BCC for 3 months or longer.

Exposures: Watchful waiting was chosen by patients and proxies regardless of this study.

Main outcome and measures: The reasons for WW and treatment were extracted from patient files and were categorized for analyses. Linear mixed models were used to estimate tumor growth and identify covariates associated with tumor growth.

Results: Watchful waiting was chosen for 280 BCCs in 89 patients (47 men [53%] and 42 women [47%]), with a median (interquartile range [IQR]) follow-up of 9 (4-15) months. The median (IQR) age of the included patients was 83 (73-88) years. Patient-related factors or preferences (ie, prioritizations of comorbidities, severe frailty, or limited life expectancy) were reasons to initiate WW in 74 (83%) patients, followed by tumor-related factors (n = 49; 55%). Treatment-related and circumstantial reasons were important for 35% and 46% of the patients, respectively. The minority of tumors increased in size (47%). Tumor growth was associated with BCC subtype (odds ratio, 3.35; 95% CI, 1.47-7.96; P = .005), but not with initial tumor size and location. The estimated tumor diameter increase was 4.46 mm (80% prediction interval, 1.42 to 7.46 mm) in 1 year for BCCs containing at least an infiltrative/micronodular component and 1.06 mm (80% prediction interval, -1.79 to 4.28 mm) for the remaining BCCs (only nodular/superficial component/clinical diagnosis). Most common reasons to initiate treatment were tumor burden or potential tumor burden, resolved reason(s) for WW, and reevaluation of patient-related factors.

Conclusions and relevance: In this cohort study of patients with BCC, WW was an appropriate approach in several patients, especially those with asymptomatic nodular or superficial BCCs and a limited life expectancy. Patients should be followed up regularly to determine whether a WW approach is still suitable and whether patients still prefer WW and to reconsider consequences of treatment and refraining from treatment.

Figure 1.. Patients’ Reasons for Choosing a Watchful Waiting (WW) Approach for Basal Cell Carcinomas (BCCs)

Values might not add up because of rounding and multiple reasons mentioned by 1 patient; in 59 (66%) patients, multiple reasons for WW (eg, both limited life expectancy [LLE] and asymptomatic) were noted in electronic patient medical records; all reasons that were mentioned are included in this graph. Examples of patient-related factors were metastasized lung carcinoma defining LLE or frailty (for instance, a combination of a Geriatric 8 score <14, cognitive impairment, dependency on others regarding activities of daily living, polypharmacy), or the prioritization of Merkel cell carcinoma or squamous cell carcinoma treatment over another BCC. Examples of circumstantial reasons were too many stressors (eg, stress owing to disease/death of a spouse or family member) and planning/logistic reasons (eg, patients going on holiday).

Figure 2.. Examples of Natural Basal Cell Carcinoma (BCC) Behavior Over Time

Time frame as indicated in the pictures represents the total time elapsed since the initial diagnosis in months. A and B, Baseline and 31-month follow-up of a biopsy-proven nodular BCC on the nose; a more evident clinical picture is seen over time. C and D, Baseline and 21-month follow-up of a biopsy-proven nodular and superficial BCC on the neck; a more evident clinical picture is seen over time. E-H, Baseline through 40-month follow-up of a biopsy-proven retroauricular nodular BCC. Histopathology after radical resection of the tumor showed both nodular and infiltrative BCC. I and J, Baseline and 11-month follow-up of a biopsy-proven infiltrative BCC of the upper lip, rapidly progressing. Additional biopsies confirmed the initial diagnosis of infiltrative BCC. K and L, Baseline and 13-month follow-up of a biopsy-proven, rapidly progressing, nodular BCC of the scalp (frontotemporal). Histopathology after radical resection of the tumor showed a squamous cell carcinoma.

Figure 3.. Algorithm for When to Consider Watchful Waiting (WW) in Patients With Basal Cell Carcinoma

In individual patients, the risks and benefits of WW and treatment can be weighed using this algorithm. The frequency of follow-up visits (eg, every 3-6 months) should be based on the feasibility for individual cases and can be adjusted (preferably by visiting a dermatology outpatient clinic when feasible; if not possible, eg, follow-up through teledermatology or general practitioner) when tumor growth is stable after 1 or 2 follow-up visits. LLE indicates limited life expectancy. ^aProceed with treatment if aligning with patient preferences and individualized treatment goals, and if benefits of treatment outweigh the risks (eg, complications, treatment burden). ^bProceed with WW if aligning with patient preferences and individualized treatment goals, and benefits of WW outweigh the risks (eg, tumor progression, burden of follow-up). Arrange follow-up including photography and reevaluation of patient-, tumor-, and treatment-related factors; instruct patient in recognizing medically dangerous progression.