Multidisciplinary Perspectives on Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Results of a National Survey

Although no statistically significant differences were found between specialties, medical oncologists demonstrated the highest level of agreement with the adoption of TNT. Specifically, 81.8% of medical oncologists agreed or strongly agreed that TNT should be the standard neoadjuvant treatment, compared to 70% of colorectal surgeons and 60% of radiation oncologists. This trend is consistent with the findings of O'Brien et al.,[] who also reported a greater inclination toward TNT among medical oncologists, likely reflecting their focus on systemic disease control. These differences may reflect variations in clinical training and therapeutic priorities across disciplines. Strengthening multidisciplinary coordination and developing unified treatment algorithms may help bridge these gaps and promote consistent implementation of TNT.[]

Tumor-specific factors emerged as the most influential elements in treatment selection. N stage (32.0%), T stage (19.4%), and tumor location (17.5%) were most frequently cited as key determinants for preferring TNT over conventional neoadjuvant options. These priorities were consistent across specialties, indicating a shared reliance on oncologic risk factors in decision-making. Our findings align with prior studies identifying nodal involvement, advanced T stage, and mesorectal fascia proximity as major considerations influencing TNT adoption.[,] Especially in low rectal tumors, anatomical constraints such as proximity to the sphincter complex further support the preference for TNT.[] Overall, these results highlight the need for personalized treatment planning based on detailed anatomical and oncological assessment, even in the context of emerging standardization efforts.

Preferences regarding the sequencing of TNT protocols varied considerably among respondents. Approximately half favored induction chemotherapy followed by radiotherapy, while the other half preferred starting with radiotherapy followed by consolidation chemotherapy. This variation reflects the ongoing global uncertainty surrounding optimal sequencing, as previously reported,[,] and may also indicate that clinicians are individualizing the order of chemotherapy and radiotherapy according to symptom burden and perceived risk of distant failure. In our study, the most frequently cited factors influencing sequencing decisions were clinical symptoms (21.3%) and nodal stage (18.4%). Radiotherapy was more often selected as the initial modality in patients presenting with symptoms such as rectal pain or bleeding, whereas induction chemotherapy was preferred in cases with a higher risk of systemic dissemination, such as those with nodal metastasis. Although the OPRA trial demonstrated higher rates of organ preservation with consolidation chemotherapy, definitive survival advantages between sequencing strategies remain unclear, which may explain the variability observed in clinical practice.[,] Initiating TNT with radiotherapy may also extend the interval to surgery, potentially allowing greater tumor regression. This prolonged interval has been associated with increased rates of clinical complete response and enhanced feasibility of organ-preserving strategies such as non-operative management.[,,]

In our study, LCRT was preferred in cases with advanced N stage, high T stage, low tumor location, or external anal sphincter invasion, reflecting a clinical emphasis on achieving optimal local control. In contrast, SCRT was more often selected for patients with poor performance status or significant comorbidities, due to its shorter duration and potentially lower toxicity. These practice patterns are supported by findings from major clinical trials. The RAPIDO study showed that SCRT followed by chemotherapy and delayed surgery reduced distant metastases compared to conventional chemoradiotherapy, although it was associated with a slightly increased risk of locoregional recurrence, emphasizing the importance of patient selection.[] The PRODIGE 23 trial, which implemented intensive induction chemotherapy before LCRT, demonstrated improved disease-free and metastasis-free survival without compromising local control, suggesting an advantage for LCRT-based TNT in high-risk patients.[] Survey studies similarly report a preference for LCRT in settings where tumor regression and sphincter preservation are prioritized,[,] and professional experience may also influence regimen selection.[] Taken together, both LCRT and SCRT are effective components of TNT, and the choice between them should be guided by tumor characteristics, patient comorbidities, and multidisciplinary evaluation to ensure personalized and effective treatment planning. In addition, real-world implementation of TNT is likely influenced by institutional resources, access to advanced technologies, and reimbursement policies.

Although these system-level factors were not directly assessed in our survey, they may further affect the feasibility and consistency of TNT delivery and warrant dedicated investigation in future studies.

This study has certain limitations that should be considered when interpreting the results. As participation was voluntary and the overall response rate was modest (36.1%), there is a risk of non response bias; physicians with a greater interest in TNT may have been more likely to participate, which could have led to an overestimation of its acceptance and use in routine practice. As we did not have access to data on non responders, we could not determine whether they differed systematically from respondents in terms of institutional type, specialty mix, or level of interest in TNT; however, such differences are possible and may limit the generalizability of our findings. Moreover, colorectal surgeons accounted for only 19.5% of respondents, despite representing almost one third of the invited sample. This underrepresentation may have restricted our ability to fully capture surgical perspectives and to detect specialty specific differences. In addition, the questionnaire was not subjected to formal psychometric validation (e.g., test-retest reliability or factor analysis), which represents an additional methodological limitation. Nevertheless, the survey reached a broad and diverse sample of physicians involved in LARC management across Türkiye. Responses were based on self-reported practices, which may not always align with actual institutional behaviors, yet they provide valuable insight into current clinical thinking. While findings are largely consistent with international data, they reflect perspectives within a specific national context and should be interpreted accordingly. Although the sample size was sufficient for descriptive analysis, further studies with larger and more balanced specialty representation are needed to validate and expand on these observations.