Search Results (47)

Introduction: ADT is routinely combined with radiotherapy (RT) for intermediate- and high-risk prostate cancer. While prostate shrinkage may facilitate planning, prospective CT-based, patient-level estimates over short, workflow-relevant intervals are scarce. Methods: We conducted a prospective study of 47 patients starting luteinizing hormone-releasing hormone agonist (LHRHa) therapy (leuprolide, 6-month depot). Prostate volumes were independently contoured by three blinded radiation oncologists on paired CT scans at baseline and ~8 weeks post-injection. The primary outcomes were the mean relative volume change and the proportion achieving a clinically relevant reduction (≥15%). PSA and testosterone were recorded at both time points; correlations and exploratory univariable logistic regression for ≥15% reduction were performed at the patient level. Results: Mean relative volume reduction ranged from −18.5% to −21.3% across observers; ≥60% of patients met the ≥15% threshold (RT-A 61.7%, RT-B 66.0%, RT-C 74.5%). PSA and testosterone decreased substantially (e.g., median PSA from 9.64 to 1.84 nmol/L) and were moderately correlated (Spearman ρ = 0.43, p = 0.002; Pearson r = 0.51, p < 0.001). No baseline clinical, histologic, or biochemical variables reached statistical significance for predicting ≥15% volume reduction; % PSA change showed a non-significant trend (OR 1.03; 95% CI 1.00–1.07; p = 0.076). Conclusions: Short-course LHRHa induced consistent CT-measured cytoreduction, with more than half of cases achieving ≥15% shrinkage within 8 weeks. Prostate downsizing was reproducible across readers and accompanied by marked PSA and testosterone declines, although biochemical responses did not predict volumetric change. These findings support incorporating a short neoadjuvant “window” before RT simulation and highlight the need for larger studies to refine predictors and compare agonist vs. antagonist trajectories. Full article

Background: Integrating deep regional hyperthermia (HT) with neoadjuvant chemoradiotherapy (CRT) may enhance treatment efficacy in locally advanced rectal cancer (LARC), yet feasibility and tolerance data remain scarce for both short-course (SCRT) and long-course (LCRT) radiotherapy (RT) regimens. Methods: In this single-center prospective observational study, 67 LARC patients received neoadjuvant RT and chemotherapy (CT) combined with deep radiative HT using a phased-array system (ALBA 4D). Patients treated with SCRT (5 × 5 Gy) were prescribed two HT sessions; those treated with LCRT (25 × 2 Gy) were prescribed ten. HT planning was guided by dedicated software, and real-time thermometry ensured precise thermal delivery. Feasibility was defined as completion of ≥50% of prescribed sessions. Tolerance and toxicity were assessed with standardized clinical scales (QMHT, UMC, CTCAE v4.03). Results: HT was feasible in both groups: 100% of SCRT and 63.6% of LCRT patients completed ≥50% of prescribed sessions. In total, 243 sessions were delivered. Most symptoms were mild and transient, predominantly localized pain. No grade ≥3 HT-related toxicities occurred. All scheduled RT and surgery proceeded without delay. Median T50 was 40.3 °C (SCRT) and 40.4 °C (LCRT); the median RT-to-HT interval was 42 min in both groups. Conclusion: This first Spanish experience shows that deep radiative HT can be seamlessly integrated into both SCRT and LCRT neoadjuvant protocols for rectal cancer. High adherence, favorable tolerance, and reliable thermal control support clinical implementation. Any between-schedule observations are descriptive only; no formal comparative testing was performed. The study was not designed or powered to establish comparative effectiveness between SCRT and LCRT, and the sample size was insufficient to detect rare HT-specific adverse events. Full article

Background: Nutritional status is a recognized determinant of treatment tolerance and clinical outcomes in oncology. This study aimed to assess body composition using computed tomography (CT) and to evaluate its association with progression-free survival (PFS) and overall survival (OS) in patients with locally advanced rectal cancer (LARC) undergoing curative multimodal therapy. Methods: A total of 216 patients with LARC who underwent neoadjuvant chemoradiotherapy (CRT) were retrospectively assessed. Two radiochemotherapy protocols were used: long-course chemoradiotherapy (lcCRT) (radiation therapy administered daily at doses of 1.8 or 2.0 Gy, for a total dose of 50.4–55.8 Gy) with concurrent chemotherapy: either 5-FU with leucovorin or capecitabine and total neoadjuvant chemoradiotherapy (tnCRT)—short-course radiotherapy (5 × 5 Gy) followed by sequential chemotherapy with CAPOX or FOLFOX. Surgery was performed 6.5 weeks after completing CRT. Radiotherapy was delivered using linear accelerators based on the Intensity-Modulated Radiation Therapy technique. CT scans were used to assess nutritional status. Survival analyses were performed. Data on food consumption frequency were collected using the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN^®). Non-Healthy-Diet-Index-14 (nHDI-14) was calculated. Results: Median observation time was 58 months (range 4–118 months). VATI level and OS (HR: 0.4618 95% CI: 0.2194–0.9719, p = 0.0419), as well as SATI and OS (HR: 0.4707 95% CI: 0.2286–0.9693, p = 0.0409) were significantly associated. This association was not significant for PFS (VATI: HR: 0.7084 95% CI: 0.4055–1.2376, p = 0.2259; SATI: HR: 0.6864 95% CI: 0.3932–1.1981, p = 0.1855). SMI and PMI values were not significantly related either PFS (SMI-HR: 0.6728, 95% CI: 0.4031–1.1231, p = 0.1295; PMI-HR: 0.7385, 95% CI: 0.4628–1.1785, p = 0.2036) or OS (SMI-HR: 0.9128, 95% CI: 0.4703–1.7720, p = 0.7876; PMI-HR: 0.6592 95% CI: 0.3684–1.1794, p = 0.1603). No significant association was found between sarcopenia development and PFS (HR: 1.2733 CI: 0.7589–2.1363; p = 0.3602) or OS (HR: 1.1207; CI: 0.5681–2.2107; p = 0.7424). Significant differences between men and women in alcohol intake and nHDI-14 were observed. Conclusions: Low visceral and subcutaneous adipose tissue index were significantly associated with worse OS in patients with LARC undergoing multimodal treatment. The nHDI-14 was negatively correlated with the duration of observation and patients’ age. Full article

Introduction: Total pelvic exenteration (TPE) is a radical procedure for advanced pelvic malignancies involving adjacent organs. The Hugo™ RAS System is a novel robotic platform, but its application in TPE has not previously been reported. We describe the first case of robotic-assisted TPE using Hugo™ RAS in a patient with locally advanced rectal cancer invading the prostate. Methods: A 69-year-old male with mucous and bloody stools was diagnosed with cT4b (prostate, levator ani muscle) N0M0 rectal cancer. After short-course radiotherapy (25 Gy/5 fractions), robotic-assisted TPE was performed. Port placement was planned to coincide with future colostomy and urostomy sites to minimize abdominal wall trauma. En bloc resection was achieved, followed by pelvic reconstruction with a gluteus maximus musculocutaneous flap and fascia lata autograft. Urinary diversion was completed with a robotic intracorporeal Wallace-type ileal conduit. Results: The operation lasted 17 h 56 min, with 175 mL blood loss. Postoperatively, Clavien–Dindo grade IIIa paralytic ileus occurred but was managed conservatively. Pathology revealed pT4b (prostate) N1a M0 disease with negative circumferential margin (11 mm). No recurrence was observed at 9 months. Conclusions: This case highlights the technical feasibility and safety of Hugo™ RAS-assisted TPE. Further clinical experience is needed to confirm reproducibility and oncologic safety. Full article

Background: Rectal cancer is common and frequently treated with neoadjuvant radiotherapy prior to surgery to reduce the risk of tumour recurrence. However, the therapeutic benefits and side effects of radiotherapy can vary between patients, and there are currently no validated biomarkers to predict treatment response. Tumour cell density (TCD) and tumour-infiltrating lymphocyte (TIL) density are proven prognostic biomarkers in colorectal cancer; however, their utility in predicting radiotherapy response remains unclear. We assessed the prognostic and predictive value of TCD and TIL density in rectal cancer patients treated with radiotherapy. Methods: TCD was quantified using a manual point-counting method in 253 pre-treatment biopsies and across the entire tumour area of 569 resection specimens from the MRC CR07 clinical trial, which randomised patients to either neoadjuvant short-course radiotherapy (SCRT) or straight to surgery (control). TIL density was measured in 102 biopsies and matched resection specimens (73 SCRT, 29 control) across different tumour areas using deep learning-based cell detection in MIM (HeteroGenius Ltd., Leeds, UK). Cutoffs for low/high-TCD and TIL density were both pre-defined and derived from survival data using the survminer R package. Survival analyses were performed to evaluate the predictive and prognostic value of TCD/TIL in relation to overall and cancer-specific survival. Results: TCD in the resection specimens was lower in the SCRT group (19.9%, IQR 12.9–26.7%) than the control group (34.3%, IQR 27.7–40.5%, p < 0.001). In control resections, low-TCD was associated with a higher risk of all-cause mortality (HR 2.20, 95% CI 1.41–3.44, p < 0.001) and cancer-related death (HR 2.69, 95% CI 1.41–5.13, p = 0.0026). In contrast, after SCRT, low resection TCD was associated with a reduced risk of death (HR 0.63, 95% CI 0.40–0.98, p = 0.04). In the SCRT group, low biopsy TCD prior to radiotherapy was associated with a reduced risk of cancer-related death (HR 0.34, 95% CI 0.13–0.89, p = 0.028). Across both trial arms, TIL density was higher in pre-treatment biopsies than resections (2492 vs. 1304/mm², p < 0.001). Low biopsy TIL density was associated with an increased risk of all-cause mortality (HR 2.43, 95% CI 1.24–4.76, p = 0.01). The SCRT group had lower TIL density in the resection compared with controls (1210 vs. 1615/mm², p < 0.001), and low resection TIL density across the whole tumour area was associated with a higher risk of death (HR 2.55, 95% CI 1.11–5.87, p = 0.027). Conclusions: Our findings support the role of TCD and TIL density as quantitative biomarkers in rectal cancer patients. TCD can be used to assess the degree of response to radiotherapy, and contrasting survival associations are observed between straight-to-surgery and SCRT-treated patients. This study raises the possibility of using TCD as both a prognostic and predictive biomarker. TIL density failed to show predictive value but demonstrated expected prognostic associations. Full article

Background/Objectives: The current standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy, or total neoadjuvant therapy (TNT), followed by total mesorectal excision (TME). If the neoadjuvant treatment results in a clinical complete response (cCR), non-operative management of LARC might be possible. It is hypothesized that cCR rates will increase with increasing radiotherapy doses. By using proton therapy, doses to organs at risk (OAR) may be decreased. In preparation for a clinical trial on dose-escalated proton therapy for LARC, the purpose of this study is to establish the feasibility of proton therapy for dose-escalated hypofractionated radiotherapy of LARC. Methods: Ten patients, having previously received short course radiotherapy (SCRT) for LARC, were included in this planning study. Two photon plans and two proton plans were created for each patient: one with a standard 5 × 5 Gy fractionation and one dose-escalated up to 5 × 7 Gy. Proton plans were robustly optimized. For all plans the integral dose (ID) was computed, and for the proton plans relative biological effectiveness (RBE) distributions were calculated. Feasibility was assessed in terms of target coverage and OAR doses. Results: All treatment plans satisfied target coverage criteria. Three of the photon and two of the proton dose-escalated plans exceeded recommended OAR objectives. Proton IDs were on average lower by a factor of 1.97 compared to photon IDs. Mean doses to OAR were, in general, lower for protons. All proton RBE values in the escalated target volumes were between 1.09 and 1.16. Conclusions: The proposed dose escalation was found to be feasible. Protons can reduce the integral dose and mean doses to OARs compared to photons in both the dose-escalated and non-escalated cases. Differences in RBE between escalated and standard fractionation were small. Full article

Background: Total neoadjuvant therapy (TNT) has emerged as a promising strategy for locally advanced rectal cancer (LARC). By administering both chemoradiotherapy (CRT) and systemic chemotherapy (CHT) pre-surgery, TNT is associated with improved disease-free survival (DFS), reduced distant metastases, and higher pathological complete response (pCR) rates. Materials and Methods: This study included patients with LARC who received various TNT schedules: induction chemotherapy (iCHT), consolidation chemotherapy (cCHT), or a combination of both (sandwichCHT). We analyzed treatment adherence, toxicity, and pathological response. Local and distant disease recurrence, as well as survival outcomes, were also evaluated. Results: Between May 2021 and January 2025, 70 patients received TNT. Treatment included iCHT (41%), sandwichCHT (49%), and cCHT (10%). Most patients (94%) received long-course radiotherapy (LCRT). Overall, TNT was well tolerated, with grade 2 gastrointestinal toxicity during CRT being the most common frequent adverse event (33%). Disease progression during TNT was noted in five patients (7%); three of these patients were receiving chemotherapy, while two underwent surgical resection of the primary tumor. A watch-and-wait strategy was adopted for five patients (7%) following TNT. Surgical procedures performed included anterior resection (92%), abdominoperineal resection (7%), and local excision (1%). Pathological assessment revealed an overall pCR rate of 30%. With a median follow-up of 17 months, no patients experienced local recurrence. Post-surgery, 10 patients (17%) developed disease progression. The median DFS was 14.7 months. Five patients (7%) died during the follow-up period, with only one death attributed to causes other than disease progression. Conclusions: In this cohort of LARC patients, TNT demonstrated favorable tolerability and encouraging short-term efficacy. Full article

Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article

Objective: The SHARON (Short course RadiatiON therapy for palliative treatment) Bone trial is a phase III randomized non-inferiority multicentric study comparing symptom relief for complicated bone metastases (BMs) achieved through hypofractionated accelerated palliative radiotherapy (RT) to a standard RT regimen. Methods: Eligible participants were adults with ECOG PS ≤ 3 who were referred for palliative RT for painful BMs. Patients were assigned to receive either 30 Gy delivered in 10 daily fractions or 20 Gy in 4 fractions over two consecutive days. The primary outcome was pain relief one month post-treatment. Pain relief and adverse events were also evaluated at 2, 3, 6, and 12 months after RT. This trial was registered at clinicaltrials.gov (NCT03503682). Results: Between February 2018 and November 2021, 83 patients were enrolled (30 Gy: 41; 20 Gy: 42). In the standard RT group, five patients did not complete the prescribed RT, while none in the experimental arm discontinued treatment (p = 0.026). Due to early mortality, the primary endpoint was evaluable in 73 patients (35 and 38 in the standard and experimental arms, respectively). The rate of complete pain response at one month was 22.9% and 28.9% in the 30 Gy and 20 Gy arms, respectively (p: 0.571). The overall pain response rates, which included complete and partial responses, were 74.3% and 78.9% in the 30 Gy and 20 Gy arms, respectively (p = 0.638), when considering at least a 2-point reduction in the numerical rating scale. In both arms, 4.8% of patients experienced Grade >2 toxicity. Conclusions: Administering 20 Gy in four fractions twice a day is non-inferior to the standard 30 Gy delivered in 10 fractions for pain relief in the context of complicated BMs. Furthermore, this regimen demonstrated comparable safety in terms of acute toxicity, with a lower incidence of definitive interruptions of radiotherapy. Full article

Background and Objectives: This study aimed to investigate the predictive and prognostic value of pre-treatment systemic inflammatory markers in patients with locally advanced rectal cancer (RC) undergoing neoadjuvant chemoradiotherapy (CRT) or radiotherapy (RT) alone. Materials and Methods: A total of 79 patients with biopsy-confirmed locally advanced RC treated at a single tertiary center between 2011 and 2017 were retrospectively analyzed. Pre-treatment blood-based inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and hemoglobin levels, were recorded. Tumor response was assessed using the Ryan tumor regression grade (TRG), and associations between laboratory parameters, treatment response, and recurrence-free survival (RFS) were evaluated. Results: Among 79 patients (mean age: 55.9 ± 11.98 years; 67.1% male), 57 received neoadjuvant CRT and 22 underwent short-course RT. Complete pathological response (pCR) was observed in 10 patients (12.7%). No statistically significant associations were found between baseline inflammatory markers and TRG, tumor differentiation, or pCR. ROC analysis revealed that none of the markers demonstrated significant discriminatory power for predicting tumor response or recurrence. However, a weak but statistically significant inverse correlation was identified between poor TRG response and higher baseline values of NLR, derived NLR, and PLR (p < 0.05). Conclusions: Inflammatory biomarkers such as NLR, PLR, and LMR, while easily accessible and cost-effective, did not demonstrate strong predictive or prognostic value in this cohort of RC patients receiving neoadjuvant therapy. These findings suggest that reliance solely on systemic inflammatory indices may be insufficient for predicting treatment outcomes, emphasizing the need for integrative models incorporating molecular and pathological markers. Full article

Background/Objectives: Predictive tools are needed to assess the response to treatment and guide treatment decisions for locally advanced rectal cancer (LARC). This study explores the value of combining the immunoscore (IS) and magnetic resonance imaging tumor regression grade (mrTRG) with pathologic and radiologic neoadjuvant rectal (NAR) scores in predicting pathologic complete response (pCRs). Methods: The scores were assessed for patients with LARC enrolled in the Averectal study (NCT03503630), who received five fractions of short-course radiotherapy, followed by six cycles of mFOLFOX-6 plus avelumab, and total mesorectal excision. The IS was calculated using the mean density percentiles of CD3- and CD8-positive T-cells on baseline biopsy samples. Baseline and post-treatment MRIs were reviewed to measure the mrTRG. NAR scores were calculated using the pre-treatment T stage and post-treatment pathologic and radiologic N and T stages. Results: Fifteen out of thirty-five patients whose data were available achieved pCR (42.8%), and seven out of fourteen patients with mrTRG = 1 (complete response) attained pCR. In patients with both a mrTRG = 1 and high IS, the pCR rate was 66.7% (6/9). All of the patients who achieved pCR had a low or intermediate pathologic NAR score with a significant correlation between pCR and pathologic NAR scores (p < 0.0001). Both pathologic and radiologic NAR scores were correlated with overall survival and disease-free survival. Conclusions: The IS can supplement the mrTRG to better predict TNT outcomes, along with the use of the NAR score. This combination could potentially help with patient selection for non-operative management and guide treatment strategies for those with different recurrence risks. Full article

Rectal cancer (RC) presents significant challenges in diagnosis and treatment, with increasing incidence among younger populations. Treatment approaches, particularly for locally advanced rectal cancer (LARC), have evolved, notably with the introduction of total neoadjuvant therapy (TNT). TNT combines neoadjuvant chemotherapy and chemoradiotherapy before surgery, improving overall survival and reducing both metastasis and local recurrence rates compared to traditional methods, while enabling more patients to complete the full oncological treatment. Clinical trials, such as RAPIDO, OPRA, and PRODIGE 23, have demonstrated the effectiveness of TNT in tumor downstaging and complete pathological responses, offering better outcomes for patients; however, debates persist regarding the role of neoadjuvant radiotherapy, with novel strategies exploring its omission in specific cases to reduce toxicity and enhance quality of life. In addition, organ preservation strategies, such as the watch-and-wait (WW) approach, have emerged as viable options for patients with a complete response to neoadjuvant therapy. Future directions point towards personalized treatment plans incorporating radiogenomics and the integration of artificial intelligence into diagnostics to optimize patient outcomes. This review aims to synthesize current treatment strategies and ongoing advancements in rectal cancer management, providing insights into potential future innovations. Full article

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2–3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences. Full article

Background: The treatment of locally advanced rectal cancer (LARC) has steadily progressed over the past four decades, with recent focus shifting towards total neoadjuvant therapy (TNT). This survey aims to elucidate the perceived surgical challenges faced by Austrian colorectal surgeons performing total mesorectal excision (TME), focusing on the increased complexity and surgical difficulty introduced by intensified treatment regimens. Methods: A comprehensive survey was conducted among Austrian colorectal surgeons to explore various aspects of managing and performing TME following TNT. The survey included questions on the general management of LARC within their institutions and utilized a five-point Likert scale to assess the respondents’ perceptions and experiences regarding surgical precision and post-operative morbidity associated with TNT. Results: A total of 31 surgeons (54% response rate) completed the survey. Regarding multidisciplinary therapy preferences, 56% of respondents preferred conventional neoadjuvant therapy regimens, with 32% favoring chemoradiotherapy and 24% opting for short-course radiotherapy, while 31% chose TNT. The majority of respondents (65%) reported quality differences in tissue dissection during TME following TNT, with 57% experiencing difficulties in identifying tissue planes and 47% noting increased tissue fragility. Increased bleeding was reported by 32% of respondents. In cases of regrowth after a watch-and-wait approach, 64% observed quality changes in tissue dissection, and 47% noted tissue fragility. Conclusions: The survey results indicate that TNT impairs surgical precision due to changes in tissue quality and challenges in identifying surgical planes. Given the critical importance of surgical precision in achieving low local recurrence rates in mid-to-low LARC, these challenges could significantly impact patient outcomes. Further prospective studies are required to elucidate the extent of these effects. Full article

Background/Objectives: The application of long-course chemoradiotherapy (LCRT) in elderly patients with locally advanced rectal cancer (LARC) can be challenging due to increased risks of complications associated with comorbidities and reduced functional status. This study aimed to assess the efficacy of neoadjuvant hypofractionated chemoradiotherapy (HCRT) in elderly patients with mid-to-low LARC. Methods: We performed a retrospective review of patients diagnosed with LARC from January 2013 to December 2020 and included those aged 70 years or older. Patients were categorized into three groups based on their treatment strategies: neoadjuvant HCRT (33 or 35 Gy in 10 fractions), neoadjuvant LCRT, and upfront surgery. Comparative analyses were performed on clinicopathological characteristics, short-term outcomes, and long-term survival outcomes among these groups. Results: Among the 296 patients included, 30 (10.1%) received HCRT, 195 (65.9%) underwent standard LCRT, and 71 (24.0%) underwent upfront surgery. The baseline characteristics showed that the HCRT group had a higher American Society of Anesthesiologists (ASA) score (ASA score 3 or 4, HCRT 43.3% vs. LCRT 16.9% vs. upfront surgery 15.5%, p = 0.002). The HCRT group showed a significantly lower incidence of radiotherapy-related complications than the LCRT group (16.7% vs. 48.7%, p = 0.001). However, the rate of pathological complete response was significantly lower in the HCRT group (10.0% vs. 15.4%, p = 0.002). The 3-year relapse-free survival (83.0% vs. 77.2% vs. 83.2%; p = 0.411), 3-year local recurrence-free survival (93.1% vs. 93.2% vs. 93.5%; p = 0.464), and 5-year overall survival (65.1% vs. 67.0% vs. 67.7%; p = 0.682) were not significantly different between the three groups. Multivariate analysis also showed that the treatment strategy was not associated with survival outcomes. Conclusions: Neoadjuvant HCRT demonstrated reduced radiotherapy-related complications and acceptable long-term oncologic outcomes. Therefore, neoadjuvant HCRT may be considered as a viable alternative for elderly patients with LARC. Full article