NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024.

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Clinical and Histological Basis of Adenosquamous Carcinoma of the Pancreas: A 30-year Experience.

BACKGROUND: Adenosquamous carcinoma (ASC) of the pancreas is a rare form of malignancy with a poor prognosis. We herein report our case series with review of the contemporary literature. METHODS: With institutional review board approval, we identified 23 patients with pancreatic ASC. RESULTS: ASC was more common in women (61%), with a median age of 73 y at presentation. The tumor was in the head of the pancreas in 65% of cases. Six cases (26%) had resectable disease, three (13%) were borderline resectable, and eight (34.7%) were locally advanced or metastatic. First-line treatment included pancreatic resection in eight cases (34.8%), concurrent neoadjuvant chemoradiation in three (13%), and neoadjuvant chemotherapy in two (8.7%). Most resected tumors had pathological T3 stage (80%). Pathological nodal disease was demonstrated in 60%, and margins were positive in three cases. Complete pathological response was not observed, although fibrosis presented in only one case (10%). Eventually, twenty patients developed metastatic disease. Overall survival is 11.5 [95% confidence interval 6, 14.5] months. CONCLUSIONS: ASC demonstrates a more aggressive malignant phenotype and carries a worse prognosis. Oncological resection is the mainstay of treatment. Neoadjuvant chemoradiation is an emerging approach in the management of ASC that has been extrapolated from the adenocarcinoma neoadjuvant trials.

Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum-Is TNT the solution?

INTRODUCTION: The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology. METHODS: A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS: CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS. CONCLUSIONS: SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.

Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

Effectiveness of Ozone Therapy as an Adjunct Treatment for Lower-Limb Ulcers: A Systematic Review.

OBJECTIVE: To evaluate the effectiveness of topical ozone therapy as an adjuvant treatment in the healing of lower limb ulcers through a systematic literature review. DATA SOURCES: Three databases were used to search for studies conducted in the period up to and including September 2020: PubMed, Scopus, and the Web of Science. STUDY SELECTION: The search identified 44 studies, 7 of which met the eligibility criteria and were evaluated. DATA EXTRACTION: Study design, study location, number of patients, patient age, type of control, wound type, intervention type, equipment used to generate ozone (ozone generation), evaluation methodology, and main results were extracted from each study. DATA SYNTHESIS: A total of 506 patients 18 years or older with chronic wounds, such as venous or diabetic ulcers, on the lower limbs were enrolled. The majority of studies addressed diabetic foot ulcers. CONCLUSIONS: The ozone therapy protocols demonstrated a healing effect in all included studies, and none reported adverse effects. This reinforces the need for more controlled and randomized clinical trials to determine the effectiveness of this treatment and establish clinical criteria for its use.

Improving clinical management of colon cancer through CONNECTION, a nation-wide colon cancer registry and stratification effort (CONNECTION II trial): rationale and protocol of a single arm intervention study.

BACKGROUND: It is estimated that around 15-30% of patients with early stage colon cancer benefit from adjuvant chemotherapy. We are currently not capable of upfront selection of patients who benefit from chemotherapy, which indicates the need for additional predictive markers for response to chemotherapy. It has been shown that the consensus molecular subtypes (CMSs), defined by RNA-profiling, have prognostic and/or predictive value. Due to postoperative timing of chemotherapy in current guidelines, tumor response to chemotherapy per CMS is not known, which makes the differentiation between the prognostic and predictive value impossible. Therefore, we propose to assess the tumor response per CMS in the neoadjuvant chemotherapy setting. This will provide us with clear data on the predictive value for chemotherapy response of the CMSs. METHODS: In this prospective, single arm, multicenter intervention study, 262 patients with resectable microsatellite stable cT3-4NxM0 colon cancer will be treated with two courses of neoadjuvant and two courses of adjuvant capecitabine and oxaliplatin. The primary endpoint is the pathological tumor response to neoadjuvant chemotherapy per CMS. Secondary endpoints are radiological tumor response, the prognostic value of these responses for recurrence free survival and overall survival and the differences in CMS classification of the same tumor before and after neoadjuvant chemotherapy. The study is scheduled to be performed in 8-10 Dutch hospitals. The first patient was included in February 2020. DISCUSSION: Patient selection for adjuvant chemotherapy in early stage colon cancer is far from optimal. The CMS classification is a promising new biomarker, but a solid chemotherapy response assessment per subtype is lacking. In this study we will investigate whether CMS classification can be of added value in clinical decision making by analyzing the predictive value for chemotherapy response. This study can provide the results necessary to proceed to future studies in which (neo) adjuvant chemotherapy may be withhold in patients with a specific CMS subtype, who show no benefit from chemotherapy and for whom possible new treatments can be investigated. TRIAL REGISTRATION: This study has been registered in the Netherlands Trial Register (NL8177) at 11-26-2019, https://www.trialregister.nl/trial/8177 . The study has been approved by the medical ethics committee Utrecht (MEC18/712).

Epidemiological guideline influence on the therapeutic trend and patient outcome of uterine cervical cancer in Japan: Japan society of gynecologic oncology guideline evaluation committee project.

OBJECTIVE: The Japan Society of Gynecologic Oncology published its first clinical guidelines for uterine cervical cancer in 2007 which has been revised twice in 2011 and 2017. The aim of this study was to investigate the influence of the first guideline publication on the therapeutic trend and patient outcome by analyzing uterine cervical cancer cases registered to the cancer registry organized by the Japan Society of Obstetrics and Gynecology. METHODS: Data of uterine cervical cancer cases registered to the cancer registry from 2000 to 2012 were provided. Epidemiological and clinical trend were analyzed by the Chi-squared test with subsequent standardized residual analysis. Overall survival among the patients registered between 2004 and 2009 was analyzed using the Fine and Gray competing risk model. RESULTS: 68,707 cases were registered during the study period. A trend analysis revealed that the guideline publication may have led to a decrease in neoadjuvant chemotherapy in parallel with an increase in radiation therapy mainly in stage II and III patients undergoing primary treatment. A survival analysis indicated that the introduction of the guideline may have improved overall survival among stage III uterine cervical cancer patients, even though a significant difference was not observed in all of the cases. CONCLUSIONS: This study demonstrated the potential influence of the guideline publication on the clinical trend and patient outcome. As this is the first assessment of the guideline for uterine cervical cancer in Japan, continuous evaluation is necessary to further comprehend the significance of this guideline.

Ultra-radical upfront surgery does not improve survival in women with advanced epithelial ovarian cancer; a natural experiment in a complete population.

OBJECTIVE: Ultra-radical surgery to achieve complete resection in advanced epithelial ovarian cancer (EOC) has been widely accepted without strong supporting data. Our objective was to assess overall survival after a structured shift to an ultra-radical upfront surgical treatment algorithm and to investigate changes in the distribution of primary treatments after this shift. PATIENTS AND METHODS: In this population-based cohort study, all women with suspected EOC in the Stockholm-Gotland region of Sweden reported to the Swedish Quality Registry for Gynecologic Cancer (SQRGC) and National Cancer Registry (NCR) were selected in two 3-year cohorts, based on year of diagnosis (before (cohort1) or after (cohort 2) change in surgical treatment algorithm) and followed for at least three years. 5-year overall survival (OS) in non-surgically and surgically treated women was analyzed. Moreover, proportional distribution of primary treatment was evaluated. RESULTS: 752 women were included in the final analysis (n = 364 and 388 in cohort 1 and 2 respectively) with a median follow-up of 29 and 27 months. The complete resection rate increased from 37 to 67% (p ≤ 0.001) as well as proportion non-surgically treated women, 24 to 33%. No improvement in OS was observed in non-surgically (HR 0.76 (95% CI, 0.58-1.01); p = 0.06) or surgically treated (HR 0.94 (95% CI, 0.75-1.18); p = 0.59) women, even when complete resection was achieved (HR 1.31 (95% CI, 0.89-1.92); p = 0.17). CONCLUSION: A shift to ultra-radical upfront surgery in EOC did not improve survival despite a significant increase in complete resection rate. Identifying the limitations of surgical treatment remains a challenge.

Management of rectal cancer in Canada: an evidence-based comparison of clinical practice guidelines

Background: Rectal cancer requires a multidisciplinary and multimodality treatment approach. Clinical practice guidelines (CPGs) provide a framework for delivering consistent, evidence-based health care. We compared provincial/territorial CPGs across Canada to identify areas of variability and evaluate their quality. Methods: We retrieved CPGs from Canadian organizations responsible for cancer care oversight and evaluated their quality and developmental methodology using the AGREE-II instrument. Recommendations for diagnostic and staging investigations, treatment by stage, and post-treatment surveillance of stage I­III rectal cancers were abstracted and compared. Results: We identified 7 sets of CPGs for analysis, varying in content, presentation, quality, and year last updated. Differences were noted in locoregional staging: 4 recommended magnetic resonance imaging over endorectal ultrasonography, 2 recommended either modality, and 3 specified scenarios for one over the other. Recommendations also varied for use of staging computed tomography of the chest versus chest radiography and for surgical management and indications for transanal excision. Recommendations for neoadjuvant therapy in stage II/III disease also differed: 3 guidelines recommended long-course chemoradiation over short-course radiation therapy alone, while 3 others recommended short-course radiation in specific clinical scenarios. Adjuvant chemotherapy for stage II/III disease was uniformly recommended, with variable protocols. The use of proctosigmoidoscopy and interval/duration of endoscopic post-treatment surveillance varied among guidelines. Conclusion: Canadian CPGs vary in their recommendations for staging, treatment, and surveillance of rectal cancer. Some of these differences reflect areas with limited definitive evidence. Consistent guidelines with uniform implementation across provinces/territories may lead to more equitable care to patients.

Contexte: Le cancer rectal requiert une approche thérapeutique multidisciplinaire et multimodalité. Les guides de pratique clinique (GPC) procurent un cadre pour assurer la prestation de soins de santé constants reposant sur des données probantes. Nous avons comparé les GPC des provinces et des territoires canadiens pour identifier les secteurs où ils varient et pour en évaluer la qualité. Méthodes: Nous avons obtenu les GPC des organisations canadiennes responsables des soins oncologiques et nous avons évalué leur qualité et la méthodologie de leur élaboration au moyen de l'outil AGREE II (Appraisal of Guidelines for Research & Evaluation). Nous avons extrait et comparé les recommandations en ce qui concerne les épreuves diagnostiques et la stadification, les traitements en fonction du stade et la surveillance post-thérapeutique du cancer rectal de stade I à III. Résultats: Nous avons recensé 7 GPC aux fins de cette analyse; leur contenu, leur présentation, leur qualité et l'année de leur plus récente mise à jour variaient. Des différences ont été observées au plan de la stadification locorégionale : 4 recommandaient l'imagerie par résonnance magnétique plutôt que l'échographie endorectale, 2 recommandaient l'une ou l'autre et 3 précisaient des circonstances où utiliser l'une plutôt que l'autre. Les recommandations variaient aussi pour ce qui est de l'utilisation de la scintigraphie c. radiographie thoracique de stadification, de la prise en charge chirurgicale et des indications de l'excision transanale. Les recommandations variaient également en ce qui concerne le traitement néoadjuvant pour la maladie de stade II/III : 3 guides recommandaient un traitement par chimioradiothérapie à long terme plutôt qu'une brève radiothérapie seule, tandis que 3 autres recommandaient une radiothérapie brève dans certains cas particuliers. La chimiothérapie adjuvante pour la maladie de stade II/III était uniformément recommandée, mais les protocoles variaient. L'utilisation de la proctosigmoïdoscopie et l'intervalle/durée de la surveillance endoscopique post-thérapeutique variaient d'un guide à l'autre. Conclusion: Les GPC canadiens varient quant à leurs recommandations pour la stadification, le traitement et la surveillance du cancer rectal. Certaines de ces différences témoignent du manque de données probantes concluantes dans certains secteurs. L'uniformisation des guides et de leur application entre les provinces et les territoires pourrait faciliter une prestation plus équitable des soins aux patients.

Impact of Genomic Assay Testing and Clinical Factors on Chemotherapy Use After Implementation of Standardized Testing Criteria.

BACKGROUND: For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention. MATERIALS AND METHODS: We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing. RESULTS: The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt. CONCLUSION: Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation. IMPLICATIONS FOR PRACTICE: This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays.

Neoadjuvant chemoradiation for patients with advanced oesophageal cancer - which response grading system best impacts prognostic discrimination?

AIMS: Neoadjuvant chemoradiation reduces tumour volume and improves the R0 resection rate, followed by extended survival for patients with advanced oesophageal cancer. The degree of tumour regression has high prognostic relevance. To date, there is still no generally accepted tumour regression grading system. The aim of this study was to compare the prognostic discrimination power of different histological regression grading systems: (i) the fibrosis/tumour ratio within the primary tumour (Mandard classification), (ii) the percentage of residual vital tumour cells (VTC) compared to the original primary tumour (Cologne Regression) and (iii) the ypT category, in patients with cT3 carcinoma of the oesophagus after neoadjuvant chemoradiation. METHODS AND RESULTS: This study included 216 patients with oesophageal cancer clinically staged as cT3NxM0 and treated from 2009 to 2012 with standardised chemoradiation followed by oesophagectomy [median age 62 years, 176 (81%) male and 138 (64%) adenocarcinoma patients]. The subgroup frequencies of the three classification systems were ypT category: ypT0 = 18%, ypT1 = 14%, ypT2 = 23%, ypT3 = 44%, ypT4 = 1%; Mandard classification: TRG1 = 18%, TRG2 = 26%, TRG3 = 24%, TRG4 = 30%, TRG5 = 2%; and Cologne Regression Scale: no tumour = 18%, 1-10% VTC = 27%, 10-50% VTC = 26% and >50% VTC = 29%. The Mandard and Cologne Regression classifications showed better prognostic differentiation for the subgroups than the ypT category. The four-tiered Cologne Regression system had a good prognostic relevance. Comparing results of the re-evaluated Cologne Regression classification with the classification by routine pathological report showed very good inter-rater agreement, with kappa value 0.891. CONCLUSION: Compared to the original primary tumour, the tumour regression grading system using the percentage of residual vital tumour has prognostic relevance.

Impact of age on the use of adjuvant treatments in patients undergoing surgery for colorectal cancer: patients with stage III colon or stage II/III rectal cancer.

BACKGROUND: Many older patients don't receive appropriate oncological treatment. Our aim was to analyse whether there are age differences in the use of adjuvant chemotherapy and preoperative radiotherapy in patients with colorectal cancer. METHODS: A prospective cohort study was conducted in 22 hospitals including 1157 patients with stage III colon or stage II/III rectal cancer who underwent surgery. Primary outcomes were the use of adjuvant chemotherapy for stage III colon cancer and preoperative radiotherapy for stage II/III rectal cancer. Generalised estimating equations were used to adjust for education, living arrangements, area deprivation, comorbidity and clinical tumour characteristics. RESULTS: In colon cancer 92% of patients aged under 65 years, 77% of those aged 65 to 80 years and 27% of those aged over 80 years received adjuvant chemotherapy (χ2trends < 0.001). In rectal cancer preoperative radiotherapy was used in 68% of patients aged under 65 years, 60% of those aged 65 to 80 years, and 42% of those aged over 80 years (χ2trends < 0.001). Adjusting by comorbidity level, tumour characteristics and socioeconomic level, the odds ratio of use of chemotherapy compared with those under age 65, was 0.3 (0.1-0.6) and 0.04 (0.02-0.09) for those aged 65 to 80 and those aged over 80, respectively; similarly, the odds ratio of use of preoperative radiotherapy was 0.9 (0.6-1.4) and 0.5 (0.3-0.8) compared with those under 65 years of age. CONCLUSIONS: The probability of older patients with colorectal cancer receiving adjuvant chemotherapy and preoperative radiotherapy is lower than that of younger patients; many of them are not receiving the treatments recommended by clinical practice guidelines. Differences in comorbidity, tumour characteristics, curative resection, and socioeconomic factors do not explain this lower probability of treatment. Research is needed to identify the role of physical and cognitive functional status, doctors' attitudes, and preferences of patients and their relatives, in the use of adjuvant therapies.

ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up.

The European Society for Medical Oncology (ESMO) consensus conference on testicular cancer was held on 3-5 November 2016 in Paris, France. The conference included a multidisciplinary panel of 36 leading experts in the diagnosis and treatment of testicular cancer (34 panel members attended the conference; an additional two panel members [CB and K-PD] participated in all preparatory work and subsequent manuscript development). The aim of the conference was to develop detailed recommendations on topics relating to testicular cancer that are not covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and where the available level of evidence is insufficient. The main topics identified for discussion related to: (1) diagnostic work-up and patient assessment; (2) stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage chemotherapy, salvage and desperation surgery and special topics; and (5) survivorship and follow-up schemes. The experts addressed questions relating to one of the five topics within five working groups. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel. A consensus vote was obtained following whole-panel discussions, and the consensus recommendations were then further developed in post-meeting discussions in written form. This manuscript presents the results of the expert panel discussions, including the consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Korean Society of Coloproctology (KSCP) trial of cONsolidation Chemotherapy for Locally advanced mid or low rectal cancer after neoadjUvant concurrent chemoraDiothErapy: a multicenter, randomized controlled trial (KONCLUDE).

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) has been a standard treatment option for locally advanced rectal cancer with improved local control. However, systemic recurrence despite neoadjuvant CRT remained unchanged. The only significant prognostic factor proven to be important was pathologic complete response (pCR) after neoadjuvant CRT. Several efforts have been tried to improve survival of patients who treated with neoadjuvant CRT and to achieve more pCR including adding cytotoxic chemotherapeutic agents, chronologic modification of chemotherapy schedule or adding chemotherapy during the perioperative period. Consolidation chemotherapy is adding several cycles of chemotherapy between neoadjuvant CRT and TME. It could increase pCR rate, subsequently could show better oncologic outcomes. METHODS: Patients with advanced mid or low rectal cancer who received neoadjuvant CRT will be included after screening. They will be randomized and assigned to undergo TME followed by 8 cycles of adjuvant chemotherapy (control arm) or receive 3 cycles of consolidation chemotherapy before TME, and receive 5 cycles of adjuvant chemotherapy (experimental arm). The primary endpoints are pCR and 3-year disease-free survival (DFS), and the secondary endpoints are radiotherapy-related complications, R0 resection rate, tumor response rate, surgery-related morbidity, and peripheral neuropathy at 3 year after the surgery. The authors hypothesize that the experimental arm would show a 15% improvement in pCR (15 to 30%) and in 3-year DFS (65 to 80%), compared with the control arm. The accrual period is 2 years and the follow-up period is 3 years. Based on the superiority design, one-sided log-rank test with α-error of 0.025 and a power of 80% was conducted. Allowing for a drop-out rate of 10%, 358 patients (179 per arm) will need to be recruited. Patients will be followed up at every 3 months for 2 years and then every 6 months for 3 years after the last patient has been randomized. DISCUSSION: KONCLUDE trial aims to investigate whether consolidation chemotherapy shows better pCR and 3-year DFS than adjuvant chemotherapy alone for the patients who received neoadjuvant CRT for locally advanced rectal cancer. This trial is expected to provide evidence to support clear treatment guidelines for patients with locally advanced rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov NCT02843191 (First posted on July 25, 2016).

Evaluation of a Completion Total Mesorectal Excision in Patients After Local Excision of Rectal Cancer: A Word of Caution.

Background: According to Dutch guidelines, locally excised, low-risk, pT1 or ypT0-1 rectal cancer should not necessarily be followed by completion total mesorectal excision (cTME) in contrast to rectal cancers with higher T stages or unfavorable features. This study evaluated cTME after local excision at a national level with possible determinants for decision-making. Methods: All patients in the Dutch Colorectal Audit (DCRA) who underwent local excision of rectal cancer between 2012 and 2015 were included. Guideline adherence for performing cTME was determined with univariate and multivariate analyses to identify factors related to noncompliance. Results: According to the guidelines, of 530 included patients, cTME was indicated in 283 (53%), and among those, was performed in 82 (29%). Guideline adherence for performing cTME improved significantly (P<.001), from 10% in 2012 to 44% in 2015. Lower Charlson comorbidity index in patients with high-risk pT1 rectal cancer and younger patients (aged 61-70 years vs ≥80 years) with pT≥2 rectal cancer were associated with increased performance of cTME (odds ratio [OR], 13.50; 95% CI, 1.39-131.32, and OR, 6.25; 95% CI, 1.83-21.31, respectively). Conclusions: In this population-based study from the Netherlands, only a minority of patients underwent cTME after local excision of rectal cancer with pathologic features indicating the need for further treatment according to the guidelines. Although the percentage of patients undergoing cTME increased over time, the study indicated a tendency toward rectal-preserving treatment with potential oncologic risks.

Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection.

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

Management of Locoregional Rectal Cancer.

The NCCN Guidelines for Rectal Cancer are now more closely aligned with those for colon cancer. A new MRI-based definition of the rectum has been included and the use of MRI in staging has been elevated in importance. There is a new emphasis on neoadjuvant therapy, especially the concurrent use of chemotherapy and radiotherapy. One of the biggest changes is more acceptance of an observational approach-"watch and wait, nonoperative management"-for select patients experiencing a complete clinical response with no evidence of residual disease after neoadjuvant therapy.

Evolving Treatment Paradigm in the Treatment of Locally Advanced Rectal Cancer.

Locally advanced rectal cancer (LARC) carries higher risks of local and distant recurrence when treated with surgical resection alone. Multiple treatment strategies have been investigated to reduce recurrence risk and improve survival. Currently, there are 3 primary strategies for managing LARC: (1) preoperative long-course radiotherapy (RT) combined with radiosensitizing chemotherapy, which is better tolerated than postoperative chemoradiotherapy and provides tumor downstaging and improved pathologic complete response (pCR), followed by postoperative chemotherapy; (2) preoperative short-course RT alone as an alternative strategy for reducing the risk of local recurrence, followed by adjuvant postoperative chemotherapy; and (3) total neoadjuvant therapy with induction chemotherapy followed by chemoradiotherapy to improve pCR and reduce the difficulty of delivering chemotherapy in the postoperative setting. In addition to these currently recommended treatment paradigms, promising new strategies are available for treatment reduction. Neoadjuvant chemotherapy alone may allow for omission of RT in select patients with favorable LARC. For patients who have complete clinical responses to neoadjuvant chemotherapy and RT, nonoperative management is being considered for sphincter preservation, with surgery used as salvage. These are active areas of investigation in both institutional and cooperative group trials. The results are anticipated to provide better tailoring of neoadjuvant therapy based on patient tumor and disease response characteristics.