Neoadjuvant Short- Vs. Long-Course Radiation for Locally Advanced Rectal Cancer: How to Choose.

OPINION STATEMENT: Over the past decades, the treatment of locally advanced rectal cancer has evolved dramatically due to improvements in diagnostic imaging, surgical technique, and the addition of radiotherapy and/or chemotherapy. Fractionation of neoadjuvant radiotherapy with or without concurrent chemotherapy remains the subject of discussion and the question multiple recent trials have aimed to answer. In light of recent data and concern for locoregional recurrence, our institution favors long-course chemoradiation in most cases, especially in low-lying primaries, threatened circumferential resection margin, consideration of non-operative management, or if the surgeon has concerns for resectability. Exceptions would include cases of oligometastatic disease planned for metastasectomy in which curative-intent treatment was pursued or if additional factors required a reduction in treatment time.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

The Society of Thoracic Surgeons/American Society for Radiation Oncology Updated Clinical Practice Guidelines on Multimodality Therapy for Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Host species differences in the thermal mismatch of host-parasitoid interactions.

Extreme high temperatures associated with climate change can affect species directly, and indirectly through temperature-mediated species interactions. In most host-parasitoid systems, parasitization inevitably kills the host, but differences in heat tolerance between host and parasitoid, and between different hosts, may alter their interactions. Here, we explored the effects of extreme high temperatures on the ecological outcomes - including, in some rare cases, escape from the developmental disruption of parasitism - of the parasitoid wasp, Cotesia congregata, and two co-occurring congeneric larval hosts, Manduca sexta and M. quinquemaculata. Both host species had higher thermal tolerance than C. congregata, resulting in a thermal mismatch characterized by parasitoid (but not host) mortality under extreme high temperatures. Despite parasitoid death at high temperatures, hosts typically remain developmentally disrupted from parasitism. However, high temperatures resulted in a partial developmental recovery from parasitism (reaching the wandering stage at the end of host larval development) in some host individuals, with a significantly higher frequency of this partial developmental recovery in M. quinquemaculata than in M. sexta. Hosts species also differed in their growth and development in the absence of parasitoids, with M. quinquemaculata developing faster and larger at high temperatures relative to M. sexta. Our results demonstrate that co-occurring congeneric species, despite shared environments and phylogenetic histories, can vary in their responses to temperature, parasitism and their interaction, resulting in altered ecological outcomes.

Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Hypoxia tolerance, but not low pH tolerance, is associated with a latitudinal cline across populations of Tigriopus californicus.

Intertidal organisms must tolerate daily fluctuations in environmental parameters, and repeated exposure to co-occurring conditions may result in tolerance to multiple stressors correlating. The intertidal copepod Tigriopus californicus experiences diurnal variation in dissolved oxygen levels and pH as the opposing processes of photosynthesis and cellular respiration lead to coordinated highs during the day and lows at night. While environmental parameters with overlapping spatial gradients frequently result in correlated traits, less attention has been given to exploring temporally correlated stressors. We investigated whether hypoxia tolerance correlates with low pH tolerance by separately testing the hypoxia and low pH stress tolerance separately of 6 genetically differentiated populations of T. californicus. We independently checked for similarities in tolerance for each of the two stressors by latitude, sex, size, and time since collection as predictors. We found that although hypoxia tolerance correlated with latitude, low pH tolerance did not, and no predictor was significant for both stressors. We concluded that temporally coordinated exposure to low pH and low oxygen did not result in populations developing equivalent tolerance for both. Although climate change alters several environmental variables simultaneously, organisms' abilities to tolerate these changes may not be similarly coupled.

Frequent Paternal Mitochondrial Inheritance and Rapid Haplotype Frequency Shifts in Copepod Hybrids.

Mitochondria are assumed to be maternally inherited in most animal species, and this foundational concept has fostered advances in phylogenetics, conservation, and population genetics. Like other animals, mitochondria were thought to be solely maternally inherited in the marine copepod Tigriopus californicus, which has served as a useful model for studying mitonuclear interactions, hybrid breakdown, and environmental tolerance. However, we present PCR, Sanger sequencing, and Illumina Nextera sequencing evidence that extensive paternal mitochondrial DNA (mtDNA) transmission is occurring in inter-population hybrids of T. californicus. PCR on four types of crosses between three populations (total sample size of 376 F1 individuals) with 20% genome-wide mitochondrial divergence showed 2% to 59% of F1 hybrids with both paternal and maternal mtDNA, where low and high paternal leakage values were found in different cross directions of the same population pairs. Sequencing methods further verified nucleotide similarities between F1 mtDNA and paternal mtDNA sequences. Interestingly, the paternal mtDNA in F1s from some crosses inherited haplotypes that were uncommon in the paternal population. Compared to some previous research on paternal leakage, we employed more rigorous methods to rule out contamination and false detection of paternal mtDNA due to non-functional nuclear mitochondrial DNA fragments. Our results raise the potential that other animal systems thought to only inherit maternal mitochondria may also have paternal leakage, which would then affect the interpretation of past and future population genetics or phylogenetic studies that rely on mitochondria as uniparental markers.

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

Transfer learning for fluence map prediction in adrenal stereotactic body radiation therapy.

Objective:To design a deep transfer learning framework for modeling fluence map predictions for stereotactic body radiation therapy (SBRT) of adrenal cancer and similar sites that usually have a small number of cases.Approach:We developed a transfer learning framework for adrenal SBRT planning that leverages knowledge in a pancreas SBRT planning model. Treatment plans from the two sites had different dose prescriptions and beam settings but both prioritized gastrointestinal sparing. A base framework was first trained with 100 pancreas cases. This framework consists of two convolutional neural networks (CNN), which predict individual beam doses (BD-CNN) and fluence maps (FM-CNN) sequentially for 9-beam intensity-modulated radiation therapy (IMRT) plans. Forty-five adrenal plans were split into training/validation/test sets with the ratio of 20/10/15. The base BD-CNN was re-trained with transfer learning using 5/10/15/20 adrenal training cases to produce multiple candidate adrenal BD-CNN models. The base FM-CNN was directly used for adrenal cases. The deep learning (DL) plans were evaluated by several clinically relevant dosimetric endpoints, producing a percentage score relative to the clinical plans.Main results:Transfer learning significantly reduced the number of training cases and training time needed to train such a DL framework. The adrenal transfer learning model trained with 5/10/15/20 cases achieved validation plan scores of 85.4/91.2/90.7/89.4, suggesting that model performance saturated with 10 training cases. Meanwhile, a model using all 20 adrenal training cases without transfer learning only scored 80.5. For the final test set, the 5/10/15/20-case models achieved scores of 73.5/75.3/78.9/83.3.Significance:It is feasible to use deep transfer learning to train an IMRT fluence prediction framework. This technique could adapt to different dose prescriptions and beam configurations. This framework potentially enables DL modeling for clinical sites that have a limited dataset, either due to few cases or due to rapid technology evolution.

Deep Learning-Based Fluence Map Prediction for Pancreas Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost.

PURPOSE: Treatment planning for pancreas stereotactic body radiation therapy (SBRT) is a challenging task, especially with simultaneous integrated boost treatment approaches. We propose a deep learning (DL) framework to accurately predict fluence maps from patient anatomy and directly generate intensity modulated radiation therapy plans. METHODS AND MATERIALS: The framework employs 2 convolutional neural networks (CNNs) to sequentially generate beam dose prediction and fluence map prediction, creating a deliverable 9-beam intensity modulated radiation therapy plan. Within the beam dose prediction CNN, axial slices of combined structure contour masks are used to predict 3-dimensional (3D) beam doses for each beam. Each 3D beam dose is projected along its beam's-eye-view to form a 2D beam dose map, which is subsequently used by the fluence map prediction CNN to predict its fluence map. Finally, the 9 predicted fluence maps are imported into the treatment planning system to finalize the plan by leaf sequencing and dose calculation. One hundred patients receiving pancreas SBRT were retrospectively collected for this study. Benchmark plans with unified simultaneous integrated boost prescription (25/33 Gy) were manually optimized for each case. The data set was split into 80/20 cases for training and testing. We evaluated the proposed DL framework by assessing both the fluence maps and the final predicted plans. Further, clinical acceptability of the plans was evaluated by a physician specializing in gastrointestinal cancer. RESULTS: The DL-based planning was, on average, completed in under 2 minutes. In testing, the predicted plans achieved similar dose distribution compared with the benchmark plans (-1.5% deviation for planning target volume 33 V33Gy), with slightly higher planning target volume maximum (+1.03 Gy) and organ at risk maximum (+0.95 Gy) doses. After renormalization, the physician rated 19 cases clinically acceptable and 1 case requiring minor improvement. CONCLUSIONS: The DL framework can effectively plan pancreas SBRT cases within 2 minutes. The predicted plans are clinically deliverable, with plan quality approaching that of manual planning.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

Fostering Radiation Oncology Physician Scientist Trainees Within a Diverse Workforce: The Radiation Oncology Research Scholar Track.

There is a need to foster future generations of radiation oncology physician scientists, but the number of radiation oncologists with sufficient education, training, and funding to make transformative discoveries is relatively small. A large number of MD/PhD graduates have entered he field of radiation oncology over the past 2 decades, but this has not led to a significant cohort of externally funded physician scientists. Because radiation oncologists leading independent research labs have the potential to make transformative discoveries that advance our field and positively affect patients with cancer, we created the Duke Radiation Oncology Research Scholar (RORS) Program. In crafting this program, we sought to eliminate barriers preventing radiation oncology trainees from becoming independent physician scientists. The RORS program integrates the existing American Board of Radiology Holman Pathway with a 2-year post-graduate medical education instructor position with 80% research effort at the same institution. We use a separate match for RORS and traditional residency pathways, which we hope will increase the diversity of our residency program. Since the inception of the RORS program, we have matched 2 trainees into our program. We encourage other radiation oncology residency programs at peer institutions to consider this training pathway as a means to foster the development of independent physician scientists and a diverse workforce in radiation oncology.

An Interpretable Planning Bot for Pancreas Stereotactic Body Radiation Therapy.

PURPOSE: Pancreas stereotactic body radiation therapy (SBRT) treatment planning requires planners to make sequential, time-consuming interactions with the treatment planning system to reach the optimal dose distribution. We sought to develop a reinforcement learning (RL)-based planning bot to systematically address complex tradeoffs and achieve high plan quality consistently and efficiently. METHODS AND MATERIALS: The focus of pancreas SBRT planning is finding a balance between organ-at-risk sparing and planning target volume (PTV) coverage. Planners evaluate dose distributions and make planning adjustments to optimize PTV coverage while adhering to organ-at-risk dose constraints. We formulated such interactions between the planner and treatment planning system into a finite-horizon RL model. First, planning status features were evaluated based on human planners' experience and defined as planning states. Second, planning actions were defined to represent steps that planners would commonly implement to address different planning needs. Finally, we derived a reward system based on an objective function guided by physician-assigned constraints. The planning bot trained itself with 48 plans augmented from 16 previously treated patients, and generated plans for 24 cases in a separate validation set. RESULTS: All 24 bot-generated plans achieved similar PTV coverages compared with clinical plans while satisfying all clinical planning constraints. Moreover, the knowledge learned by the bot could be visualized and interpreted as consistent with human planning knowledge, and the knowledge maps learned in separate training sessions were consistent, indicating reproducibility of the learning process. CONCLUSIONS: We developed a planning bot that generates high-quality treatment plans for pancreas SBRT. We demonstrated that the training phase of the bot is tractable and reproducible, and the knowledge acquired is interpretable. As a result, the RL planning bot can potentially be incorporated into the clinical workflow and reduce planning inefficiencies.

Tolerance Patterns and Transcriptomic Response to Extreme and Fluctuating Salinities across Populations of the Intertidal Copepod Tigriopus californicus.

AbstractPopulations that tolerate extreme environmental conditions with frequent fluctuations can give valuable insights into physiological limits and adaptation. In some estuarine and marine ecosystems, organisms must adapt to extreme and fluctuating salinities, but not much is known about how varying salinities impact local adaptation across a wide geographic range. We used eight geographically and genetically divergent populations of the intertidal copepod Tigriopus californicus to test whether northern populations have greater tolerance to low salinity stresses, as they experience greater precipitation and less evaporation. We used a common-garden experiment approach and exposed all populations to acute low (1 and 3 ppt) and high (110 and 130 ppt) salinities for 24 h and to a fluctuation between baseline salinity and moderate low (7 ppt) and high (80 ppt) salinities for over 49 h. We also performed RNA sequencing at several time points during the fluctuation between baseline and salinity of 7 ppt to understand the molecular basis of divergence between two populations with differing physiological responses. We present these novel findings: (1) acute low salinity conditions caused more deaths than high salinity; (2) molecular processes that elevate proline levels increased in salinity of 7 ppt, which contrasts with other physiological studies in T. californicus that mainly associated accumulation of proline with hyperosmotic stress; and (3) tolerance to a salinity fluctuation did not follow a latitudinal trend but was instead governed by a complex interplay of factors, including population and duration of salinity stress. This highlights the importance of including a wider variety of environmental conditions in empirical studies to understand local adaptation.

NCCN Guidelines Insights: Rectal Cancer, Version 6.2020.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E- or HER2 amplification-positive disease.

Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with locally advanced esophageal cancer. METHODS: ASCO convened an Expert Panel to conduct a systematic review of the more recently published literature (1999-2019) on therapy options for patients with locally advanced esophageal cancer and provide recommended care options for this patient population. RESULTS: Seventeen randomized controlled trials met the inclusion criteria. Where possible, data were extracted separately for squamous cell carcinoma and adenocarcinoma. RECOMMENDATIONS: Multimodality therapy for patients with locally advanced esophageal carcinoma is recommended. For the subgroup of patients with adenocarcinoma, preoperative chemoradiotherapy or perioperative chemotherapy should be offered. For the subgroup of patients with squamous cell carcinoma, preoperative chemoradiotherapy or chemoradiotherapy without surgery should be offered. Additional subgroup considerations are provided to assist with implementation of these recommendations. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Evaluating treatment protocols for rectal squamous cell carcinomas: the Duke experience and literature.

BACKGROUND: Colorectal cancer is the third most common cancer in the United States and associated with significant morbidity and mortality. Within colorectal cancer histologies, squamous cell carcinomas (SCC) are rare compared to adenocarcinomas, with only about 200 cases reported to date. Because rectal SCC is rarely encountered, there is a lack of literature and clinical consensus surrounding its optimal treatment approach. Staging and management of SCC can be partly analogous to both rectal adenocarcinoma and anal canal SCC, which leads to a dilemma in how to best approach these patients. As large randomized prospective trials are unrealistic in the setting of this rare malignancy, this study evaluates an institutional experience and reviews the existing literature to help guide future management approaches. METHODS: This retrospective study compared various treatment regimens for rectal SCC patients treated at Duke University Medical Center from January 1, 1980 through December 31, 2016. Patients ≥18 years old with histologically confirmed, nonmetastatic rectal SCC were included. Due to small sample size, all statistical analyses were descriptive. For our systematic review, a comprehensive search of PubMed from 1933 to March 2018 was performed, with selected articles referenced to ensure all relevant publications were included. A qualitative analysis was performed to examine patient diagnoses, treatments, and disease- and treatment-related outcomes. RESULTS: Eight patients were included. Three patients underwent initial, curative attempt surgery and two of these patients required colostomy. With follow-up ranging from 7.1 to 31.5 months, one patient was alive with no evidence of disease while two developed local/regional recurrences. Five patients received definitive chemoradiation. Of these, three patients developed local/regional and/or metastatic recurrence. Two patients achieved complete response on imaging and currently remain disease-free (follow-up of 31.5 and 33.6 months). CONCLUSIONS: Although the review of our institutional experience is limited by small numbers, our analysis suggests that definitive chemoradiation therapy is the preferred treatment approach to rectal SCC based on improved disease-related outcomes, sphincter preservation and morbidity profiles. This conclusion is supported by a systematic literature review.

Multi-Institutional Analysis of Synchronous Prostate and Rectosigmoid Cancers.

Purpose: To perform a multi-institutional analysis of patients with synchronous prostate and rectosigmoid cancers. Materials and Methods: A retrospective review of Duke University and Durham Veterans Affairs Medical Center records was performed for men with both prostate and rectosigmoid adenocarcinomas from 1988 to 2017. Synchronous presentation was defined as symptoms, diagnosis, or treatment of both cancers within 12 months of each other. The primary study endpoint was overall survival. Univariate and multivariable Cox regression was performed. Results: Among 31,883 men with prostate cancer, 330 (1%) also had rectosigmoid cancer and 54 (16%) of these were synchronous. Prostate cancer was more commonly the initial diagnosis (59%). Fifteen (28%) underwent prostatectomy or radiotherapy before an established diagnosis of rectosigmoid cancer. Stage I, II-III, or IV rectosigmoid cancer was present in 26, 57, and 17% of men, respectively. At a median follow-up of 43 months, there were 18 deaths due rectosigmoid cancer and two deaths due to prostate cancer. Crude late grade ≥3 toxicities include nine (17%) gastrointestinal and six (11%) genitourinary. Two anastomotic leaks following low anterior resection occurred in men who received a neoadjuvant radiotherapy prostate dose of 70.6-76.4 Gy. Rectosigmoid cancer stages II-III (HR 4.3, p = 0.02) and IV (HR 16, p < 0.01) as well as stage IV prostate cancer (HR 31, p < 0.01) were associated with overall survival on multivariable analysis. Conclusions: Synchronous rectosigmoid cancer is a greater contributor to mortality than prostate cancer. Men aged ≥45 with localized prostate cancer should undergo colorectal cancer screening prior to treatment to evaluate for synchronous rectosigmoid cancer.