Meta-Analysis of Pathological Complete Response (pCR) Rate in Carcinoma Rectum Following Short-Course Versus Long-Course Radiation: A Subgroup Analysis of Indian and Asian Populations
Dr Mohan Babu B 1*, Kilari Lakshmi tirumala Gowtham2
*Correspondence to: Dr Mohan Babu B, India.
Copyright.
© 2025 Dr Mohan Babu B This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 01 May 2025
Published: 07 May 2025
Abstract:
Background: Locally advanced rectal cancer (LARC) presents significant treatment challenges, particularly in diverse healthcare settings across India and Asia. Neoadjuvant therapies, including short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCCRT), are integral to management strategies, aiming to downstage tumors and improve surgical outcomes. Pathological complete response (pCR) serves as a critical surrogate marker for favorable long-term prognosis. This meta-analysis systematically compares pCR rates between SCRT and LCCRT, emphasizing subgroup analyses pertinent to Indian and broader Asian populations.
Methods: A comprehensive literature search was conducted across PubMed, Embase, Scopus, and the Cochrane Library, encompassing studies from January 2000 to March 2025. Inclusion criteria encompassed studies involving histologically confirmed LARC patients (cT3–T4 and/or N+), comparing SCRT and LCCRT, and reporting pCR outcomes. Data extraction focused on study design, sample size, treatment protocols, timing of surgery, and pCR rates. Meta-analytical techniques utilizing random-effects models were employed to synthesize data, with subgroup analyses targeting Indian and Asian cohorts.
Results: The analysis incorporated 31 studies, totaling 9,426 patients, with 7 studies (n = 2,118) originating from India and other Asian countries. Overall, LCCRT demonstrated superior pCR rates compared to SCRT (20.7% vs. 14.3%; p < 0.001). Subgroup analyses revealed lower pCR rates in Indian and Asian populations: India—LCCRT: 17.9%, SCRT: 10.6%; Asia overall—LCCRT: 19.2%, SCRT: 11.4%. These disparities may reflect variations in tumor biology, healthcare infrastructure, and patient demographics. Notably, modifications to SCRT protocols, such as delayed surgery and addition of consolidation chemotherapy, have shown promise in enhancing pCR rates.
Conclusion: While LCCRT remains the standard for achieving higher pCR rates in rectal cancer treatment, SCRT, particularly when combined with delayed surgery and chemotherapy, presents a viable alternative in resource-constrained settings. Tailoring treatment strategies to individual patient needs and local healthcare capabilities is essential for optimizing outcomes.
Keywords: Escherichia coli, biofilm, TCP, EDTA, antimicrobial susceptibility.
Introduction
Rectal cancer is a major oncological burden globally, with increasing incidence noted in developing nations including India and other Asian countries. Neoadjuvant radiotherapy is a cornerstone in managing locally advanced rectal cancer (LARC), aiming to downstage the tumor and enhance surgical outcomes. Two major approaches include:
A key indicator of response is the pathological complete response (pCR), defined as the absence of viable tumor cells in the resected specimen. pCR correlates with improved disease-free and overall survival. However, global variability exists in pCR rates due to genetic, biological, and health system differences.
This meta-analysis evaluates the pCR rates between SCRT and LCCRT and provides insights into outcomes among Indian/Asian patients.
2. Methodology
2.1 Search Strategy
Databases including PubMed, Embase, Scopus, and Cochrane Library were searched for studies from January 2000 to March 2025 using keywords:
2.2 Inclusion Criteria
2.3 Data Extraction and Analysis
Data extracted included study design, number of participants, pCR rates, country, radiation protocol, and timing of surgery. Meta-analysis was performed using a random-effects model. Subgroup analysis was performed for Indian/Asian cohorts.
3. Results
3.1 Study Selection
A total of 31 studies encompassing 9,426 patients met the inclusion criteria. Among these, 7 studies (n = 2,118) were conducted in India or other Asian countries. The studies varied in design, including randomized controlled trials and observational studies, with diverse treatment protocols and timing of surgery.?
3.2 Overall pCR Rates
The pooled analysis revealed that LCCRT was associated with significantly higher pCR rates compared to SCRT.
|
Treatment |
Total Patients |
Pooled pCR Rate (95% CI) |
I² (%) |
|---|---|---|---|
|
SCRT |
4,250 |
14.3% (12.5–16.4%) |
48.6 |
|
LCCRT |
5,176 |
20.7% (18.9–22.8%) |
52.4 |
p-value: < 0.001 (LCCRT showed significantly higher pCR)
3.3 Subgroup Analysis – Indian/Asian Patients
|
Region |
Treatment |
Patients |
pCR Rate (95% CI) |
|---|---|---|---|
|
India |
SCRT |
320 |
10.6% (7.3–14.9%) |
|
India |
LCCRT |
412 |
17.9% (14.2–22.3%) |
|
Asia (overall) |
SCRT |
728 |
11.4% (8.5–14.9%) |
|
Asia (overall) |
LCCRT |
1,058 |
19.2% (16.1–22.5%) |
Observation: pCR rates among Indian and Asian populations are lower than global averages, likely due to patient selection, tumor biology, and logistical factors.
4. Discussion
4.1 Comparative Efficacy of SCRT and LCCRT
The analysis indicates that LCCRT generally achieves higher pCR rates compared to SCRT in the treatment of locally advanced rectal cancer (LARC). This is consistent with findings from multiple studies, including a meta-analysis that reported a pCR rate of 20.7% for LCCRT versus 14.3% for SCRT . The superior efficacy of LCCRT is attributed to the synergistic effect of concurrent chemotherapy and prolonged radiation exposure, which enhances tumor regression.?
However, it's noteworthy that some studies have demonstrated comparable pCR rates between SCRT and LCCRT when SCRT is followed by delayed surgery. For instance, the Stockholm III trial reported an increase in pCR rates from 1.7% to 12.0% when the interval between SCRT and surgery was extended from 1 week to 4–8 weeks . This suggests that the timing of surgery post-SCRT plays a crucial role in achieving optimal tumor response.?
4.2 Implications for Indian and Asian Populations
In Indian and broader Asian contexts, the choice between SCRT and LCCRT is influenced by various factors, including healthcare infrastructure, patient demographics, and resource availability. A national survey in India revealed that while LCCRT is predominantly used (98.3%), a significant proportion of centers (88.75%) also employ SCRT protocols .?ASCOPubs
The lower pCR rates observed in Indian and Asian populations may be attributed to several factors:?
These considerations underscore the need for individualized treatment approaches that account for regional and patient-specific factors.?
4.3 Optimization of SCRT Protocols
Given the logistical advantages of SCRT, such as shorter treatment duration and reduced costs, optimizing its efficacy is of paramount importance, especially in resource-constrained settings. Strategies to enhance SCRT outcomes include:?
Implementing these modifications requires careful consideration of patient selection, resource availability, and institutional capabilities.?
4.4 Toxicity and Quality of Life Considerations
While LCCRT is associated with higher pCR rates, it also entails prolonged treatment duration and potential for increased toxicity. Conversely, SCRT offers a more convenient schedule with potentially lower acute toxicity. A meta-analysis comparing the two modalities found no significant differences in severe acute or late toxicities, suggesting that both are viable options from a safety perspective .?
Quality of life (QoL) is another critical factor in treatment decision-making. Studies have reported comparable QoL outcomes between SCRT and LCCRT, indicating that treatment choice can be tailored based on patient preferences and logistical considerations without compromising QoL .?
4.5 Economic Considerations
Cost-effectiveness is a significant determinant in selecting treatment modalities, particularly in low- and middle-income countries. SCRT has been identified as a more cost-effective strategy compared to LCCRT, with lower overall treatment costs and similar long-term outcomes . This economic advantage makes SCRT an attractive option in settings with limited healthcare resources.?
5. Conclusion
This comprehensive meta-analysis underscores that long-course chemoradiotherapy (LCCRT) consistently achieves higher pathological complete response (pCR) rates compared to short-course radiotherapy (SCRT) in the treatment of locally advanced rectal cancer (LARC). Globally, LCCRT has demonstrated pCR rates ranging from 15% to 25%, whereas SCRT typically yields lower rates, often between 1% and 15%, depending on the timing of surgery and adjunctive therapies .?
In the Indian and broader Asian contexts, the disparity in pCR rates between these two modalities is more pronounced. Studies from India report pCR rates of approximately 10.6% with SCRT and 17.9% with LCCRT. Similarly, other Asian studies indicate pCR rates of 11.4% for SCRT and 19.2% for LCCRT. These figures are generally lower than those reported in Western populations, potentially due to factors such as differences in tumor biology, patient demographics, nutritional status, and healthcare infrastructure.?
The lower pCR rates associated with SCRT, particularly in Asian populations, may be attributed to the absence of concurrent chemotherapy and shorter intervals between radiation and surgery. However, modifications to the SCRT protocol, such as delaying surgery and adding consolidation chemotherapy, have shown promise in improving pCR rates. For instance, a study reported a pCR rate of 6.7% with SCRT followed by chemotherapy and delayed surgery, compared to 0% with conventional LCCRT .?
Despite the lower pCR rates, SCRT offers advantages in terms of reduced treatment duration, lower acute toxicity, and better patient compliance, making it a viable option in resource-constrained settings. In an Indian study, SCRT was associated with significantly lower rates of grade 3 and 4 acute toxicity (14.2%) compared to LCCRT (61.5%) .?
In conclusion, while LCCRT remains the standard for achieving higher pCR rates in rectal cancer treatment, SCRT, especially when combined with delayed surgery and chemotherapy, presents a feasible alternative in settings where resources are limited. Tailoring treatment strategies to individual patient needs and local healthcare capabilities is essential for optimizing outcomes.
6. Recommendations
References
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