In a study reported in The Lancet Oncology, Fernandez et al found high rates of conditional recurrence-free survival during watch-and-wait surveillance among patients with rectal cancer who maintained clinical complete response to neoadjuvant chemotherapy for 1, 3, or 5 years.
Study Details
In the study, conditional survival modeling was performed using data on patients with rectal cancer from the International Watch & Wait Database, a large-scale registry that includes data from 47 clinics in 15 countries. The study population consisted of 793 patients who had a clinical complete response after neoadjuvant chemotherapy and were managed by a watch-and-wait strategy between November 1991 and December 2015. Patients who had undergone any surgical procedure were excluded.
The conditional survival analysis estimated the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis–free for 1, 3, and 5 years from the date of the decision to initiate the watch-and-wait strategy. The primary outcome measures were conditional local regrowth–free survival at 3 years after maintaining clinical complete response for 1 year, and conditional distant metastasis–free survival at 5 years after being distant metastasis–free for 3 years.
Among all patients:
- Baseline tumor stage was known for 82% of patients and was T1, T2, T3, and T4 in 2%, 31%, 63%, and 4%, respectively
- Nodal status was known for 85% of patients, with 57% being node-positive and 43% node-negative
- 40% had a total final radiotherapy dose of < 50.4 Gy.
Local Regrowth–Free and Distant Metastasis–Free Survival
Median follow-up was 55.2 months (interquartile range = 36.0–75.6 months). In the entire cohort, actuarial local regrowth–free survival was 83.8% at 1 year, 74.3% at 3 years, and 72.1% at 5 years; actuarial distant metastasis–free survival was 97.1% at 1 year, 91.4%, at 3 years, and 88.9% at 5 years.
Among patients maintaining clinical complete response for 1 (n = 645 at risk), 3 (n = 474 at risk), and 5 years (n = 271 at risk), the probability of remaining free from local regrowth for an additional 2 years was 88.1% (95% confidence interval [CI] = 85.8%–90.9%), 97.3% (95% CI = 95.2%–98.6%), and 98.6% (95% CI = 97.6%–100.0%).
Among patients with clinical complete response who remained distant metastasis–free for 1 (n = 738 at risk), 3 (n = 565 at risk), and 5 years (n = 328 at risk), the probability of remaining free from distant metastasis for an additional 2 years was 93.8% (95% CI = 92.3%–95.9%), 97.8% (95% CI = 96.6%–99.3%), and 96.6% (95% CI = 94.0%–98.9%).
Recurrence Risk Factors
In multivariate analysis among 506 patients with data available on each of age, sex, cT stage, cN stage, and total radiotherapy dose, significant risk factors for local regrowth were cT3–4 (69% of patients) vs cT1–2 (hazard ratio [HR] = 1.73, P = .0083) and total radiotherapy dose of < 50.4 Gy (47% of patients) vs ≥ 50.4 Gy (HR = 0.60, P = .0035, for ≥ 50.4 vs < 50.4 Gy).
Among 573 patients treated after 2010 with available baseline cT status, 31% were cT1–2 and 69% were cT3–4. Among these patients, actuarial local regrowth–free survival was 88.0% in patients with cT1–2 and 80.9% in patients with cT3 (P = .0070). Among those with clinical complete response for 1 year, the difference was less marked, with 2-year conditional local regrowth–free survival at 1 year of 95.4% vs 90.1%.
In analysis in the entire cohort, the actuarial local regrowth-free survival rates were 76.8% in those who received a total radiotherapy dose of < 50.4 Gy (40% of population) vs 85.2% in those who received ≥ 50.4 Gy (P = .014) Among those with clinical complete response for 1 year, the difference was again less marked, with 1-year conditional local regrowth–free survival of 93.5% vs 91.7%.
The investigators stated, “Conditional survival analysis estimates suggest that patients who sustain a clinical complete response for 3 years have 5% or lower risk of developing a local regrowth and a less than 2% risk of developing systemic recurrence thereafter. Although baseline cT stage and final dose of radiotherapy are known risk factors for local regrowth after an initial clinical complete response to neoadjuvant chemoradiotherapy, these risk factors appear to be less relevant after 1 year of a sustained clinical complete response.”
They concluded, “These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach.”
Rodrigo O. Perez, PhD, of the Department of Colorectal Surgery, Angelita and Joaquim Gama Institute, São Paulo, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by European Registration of Cancer Care, European Society of Surgical Oncology, Champalimaud Foundation Lisbon, and others. For full disclosures of the study authors, visit thelancet.com.
