Evolución y resultados del tratamiento neoadyuvante en cáncer de mama durante un periodo de 10 años / Progress and oncological outcome of neoadjuvant therapy in breast cancer patients during a 10-year period

Introducción: el cáncer de mama es la neoplasia más frecuente en mujeres españolas. Los continuos avances en su tratamiento han contribuido a mejorar de forma progresiva la supervivencia en estadios precoces. Entre los avances durante los últimos años, hay que destacar el tratamiento neoadyuvante.Material y métodoshemos valorado la evolución temporal de las indicaciones y los resultados del tratamiento neoadyuvante del cáncer de mama durante un periodo de 10 años. Para ello, se han analizado las características clínicas, la respuesta completa patológica (RCp), la supervivencia global (SG) y libre de progresión (SLP) de todos los pacientes con cáncer de mama tratados con neoadyuvancia entre el 1 de enero de 2007 y el 31 de diciembre de 2016.Resultadosse han tratado 212 pacientes con cáncer de mama. A lo largo de los 10 años hemos observado un progresivo aumento en el número de pacientes tratadas con neoadyuvancia, en la edad de los pacientes incluidos (p < 0,001), en los casos de menopausia (p = 0,029), de casos triple negativo y HER2 positivo. También, hemos observado un aumento en el número de casos en los que se ha realizado cirugía conservadora y biopsia selectiva del ganglio centinela.Conclusionesel tratamiento neoadyuvante se utiliza cada vez más en las pacientes con cáncer de mama, sobre todo en los subtipos de mal pronóstico (triple negativo y HER2). La incorporación de nuevos fármacos y el tratamiento de estadios más precoces está contribuyendo a la mejora de las tasas de RCp y las cirugías conservadoras. (AU)

Introduction: Breast cancer is the most frequent tumor in Spanish women. Continuous advances in the treatment of this neoplasm, have contributed to progressively improve survival in early stages. In the last years, neoadjuvant treatment has evolved and changes have occurred in the treatment indication and in the results.Material and methodsWe have assessed the temporal evolution of indications and results of neoadjuvant therapy in breast cancer over a 10-year period. We have analyzed the clinical characteristics, the complete pathological response (CRp), overall survival (OS) and progression-free survival (PFS) of all patients with breast cancer treated with neoadjuvant therapy between January 1st 2007 and December 31st 2016.ResultsDuring the study period, 212 patients were treated.  Throughout the 10-year period, we observed that increasingly older patients had been treated (p < 0.001), a greater number of menopausal patients (p = 0.029), a greater number of triple negative and HER2 positive cases. In addition, a larger number of conservative surgeries and sentinel lymph node biopsies had been performed.ConclusionsNeoadjuvant therapy is increasing in patients with breast cancer, especially in subtypes with poor prognosis (triple negative and HER2). The emerging new drugs and treatment in earlier stages has increased the rate of pCR and breast conserving surgery. (AU)

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

PURPOSE: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. RESULTS: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). CONCLUSIONS: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Incidence, treatment, and survival trends in older versus younger women with epithelial ovarian cancer from 2005 to 2018: A nationwide Danish study.

OBJECTIVE: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. METHODS: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005-09, 2010-13, 2014-18). RESULTS: We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014-18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005-09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005-09) to 84% (2014-18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). CONCLUSIONS: The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders.

The "collateral damage" of the war on COVID-19: impact of the pandemic on the care of epithelial ovarian cancer.

The covid-19 pandemic has impacted the management of non-covid-19 illnesses. Epithelial ovarian cancer (EOC) requires long-duration multidisciplinary treatment. Teleconsultation and shared care are suggested solutions to mitigate the consequences of the pandemic. However, these may be challenging to implement among patients who come from the lower economic strata. We report the disastrous impact of the pandemic on the care of EOC by comparing patients who were treated during the pandemic with those treated in the previous year. We collected the following data from newly diagnosed patients with EOC: time from diagnosis to treatment, time for completion of planned chemotherapy, and proportion of patients completing various components of therapy (surgery and chemotherapy). Patients treated between January 2019 and September 2019 (Group 1: Pre-covid) were compared with those treated between January 2020 and December 2020 (Group 2: During covid pandemic). A total of 82 patients were registered [Group 1: 43(51%) Group 2: 39(49)]. The median time from diagnosis to start of treatment was longer in group 2 when compared to group 1 [31(23-58) days versus 17(11-30) days (p = 0.03)]. The proportion of patients who had surgery in group 2 was lower in comparison to group 1 [33(77%) versus 21(54%) (p = 0.02)]. Proportion of patients who underwent neoadjuvant (NACT) and surgery were fewer in group 2 in comparison to group 1 [9(33%) versus 18(64%) p = 0.002]. Among patients planned for adjuvant chemotherapy, the median time from diagnosis to treatment was longer in group 2 [28(17-45) days, group 1 versus 49(26-78) days, group 2 (p = 0.04)]. The treatment of patients with EOC was adversely impacted due to the COVID-19 pandemic. There was a compromise in the proportion of patients completing planned therapy. Even among those who completed the treatment, there were considerable delays when compared with the pre-covid period. The impact of these compromises on the outcomes will be known with longer follow-up.

Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives.

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

Breast cancer immunotherapy: Current and novel approaches.

The crucial role of the immune system in the progression/regression of breast cancer (BC) should always be taken into account. Various immunotherapy approaches have been investigated for BC, including tumor-targeting antibodies (bispecific antibodies), adoptive T cell therapy, vaccines, and immune checkpoint blockade such as anti-PD-1. In addition, a combination of conventional chemotherapy and immunotherapy approaches contributes to improving patients' overall survival rates. Although encouraging outcomes have been reported in most clinical trials of immunotherapy, some obstacles should still be resolved in this regard. Recently, personalized immunotherapy has been proposed as a potential complementary medicine with immunotherapy and chemotherapy for overcoming BC. Accordingly, this review discusses the brief association of these methods and future directions in BC immunotherapy.

Trends in the treatment of pancreatic cancer in Japan.

Pancreatic cancer is known to have the poorest prognosis among digestive cancers. With the development of new chemotherapeutic agents and introduction of multidisciplinary therapy, however, the treatment outcomes for pancreatic cancer have dramatically improved over the past two decades. The keys to successful treatment will be accurate assessment of resectability [resectable (R), borderline resectable (BR) or unresectable (UR)] at the time of diagnosis and prompt adoption of an appropriate multidisciplinary treatment strategy. Prep-02/JSAP-05 trial which is an RCT of upfront surgery versus neoadjuvant chemotherapy using GEM and S-1 (GS) and subsequent surgery for R-PDAC in Japan indicated neoadjuvant chemotherapy had a longer overall survival (OS) than those undergoing upfront surgery (36.7M vs. 26.6M, p = 0.015). In a retrospective multicenter study in Japan reported that in BR-PDAC, median survival time (MST) in the pretreatment group was significantly better than that in the upfront surgery group (25.7 months vs. 19.0 months, p = 0.015) according to a propensity score matching analysis. Another retrospective multicenter study with UR-LA PDAC in Japan reported that conversion surgery was more beneficial for patients with more than 8 months of preoperative therapy than those with less than 8 months of that therapy. Various clinical trials on pancreatic cancer are ongoing, and the results of trials on chemotherapeutic regimens and multidisciplinary treatments will be of further interest.

Changes in and challenges regarding the surgical treatment of hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a high morbidity and mortality in China and elsewhere in the world. Due to its tumor heterogeneity and distant metastasis, patients with HCC often have a poor prognosis. A surgical treatment such as a radical hepatectomy is still the treatment of choice for patients with HCC in current clinical practice. However, the high rate of recurrence and rate of metastasis after surgery diminishes the survival of and prognosis for these patients. In an era of targeted therapy and immunotherapy, the surgical treatment of HCC must change. This review focuses on the definition, feasibility, and criteria with which to evaluate neoadjuvant therapy for HCC in order to provide a new perspective on surgical treatment of HCC.

Current trends in the treatment of HR+/HER2+ breast cancer.

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

Persistent High Rate of Positive Margins and Postoperative Complications After Surgery for cT4 Rectal Cancer at a National Level.

BACKGROUND: A more extensive resection is often required in locally advanced rectal cancer, depending on preoperative neoadjuvant treatment response. OBJECTIVE: Circumferential margin involvement and postoperative outcomes after total mesorectal excision and multivisceral resection were assessed in patients with clinical locally advanced (cT4) rectal cancer at a national level. DESIGN: This is a population-based study. SETTINGS: Data were retrieved from the Dutch Colorectal Audit. PATIENTS: A total of 2242 of 2881 patients with cT4 rectal cancer between January 2009 and December 2017 were selected. MAIN OUTCOME MEASURES: Main outcomes were resection margins, postoperative complications, and mortality. RESULTS: Multivisceral resection was performed in 936 of 2242 patients, of whom 629 underwent extended multivisceral resection. Positive circumferential margin rate was higher after multivisceral resection than after total mesorectal excision: 21.2% vs 13.9% (p < 0.001). More postoperative complications occurred after limited and extended multivisceral resections than after total mesorectal excision (44.1% and 53.8% vs 37.6%, p < 0.001). Incidence of 30-day mortality was similarly low in both groups (1.5% vs 2.2%, p = 0.20). Independent predictors of postoperative complications were age ≥70 years (OR, 1.28 [95% CI, 1.04-1.56]; p = 0.02), male sex (OR, 1.68 [95% CI, 1.38-2.04]; p< 0.001), mucinous tumors (OR, 1.55 [95% CI, 1.06-2.27]; p = 0.02), extended multivisceral resection (OR, 1.98 [95% CI, 1.56-2.52]; p< 0.001), Hartmann procedure (OR, 1.42 [95% CI, 1.07-1.90]; p = 0.02), and abdominoperineal resection (OR, 1.56 [95% CI, 1.25-1.96]; p < 0.001). LIMITATIONS: Data specifying the extent of multivisceral resections and Clavien Dindo I to II complications were not available. CONCLUSIONS: This population-based study revealed relatively high circumferential margin positivity and postoperative complication rates in patients with cT4 rectal cancer, especially after multivisceral resections, but low mortality rates. See Video Abstract at http://links.lww.com/DCR/B457. ALTA TASA PERSISTENTE DE MRGENES POSITIVOS Y COMPLICACIONES POSTOPERATORIAS DESPUS DE LA CIRUGA DE CNCER RECTAL CTA NIVEL NACIONAL: ANTECEDENTES:A menudo se requiere una resección más extensa en el cáncer de recto localmente avanzado, según la respuesta al tratamiento neoadyuvante preoperatorio.OBJETIVO:Se evaluó la afectación del margen circunferencial y los resultados postoperatorios después de la escisión mesorrectal total y la resección multivisceral en pacientes con cáncer rectal clínico localmente avanzado (cT4) a nivel nacional.DISEÑO:Este es un estudio poblacional.ENTORNO CLINICO:Los datos se recuperaron de la Auditoría colorrectal holandesa.PACIENTES:Se seleccionaron un total de 2242 de 2881 pacientes con cáncer de recto cT4 entre enero de 2009 y diciembre de 2017.PRINCIPALES MEDIDAS DE VALORACION:Los principales resultados fueron los márgenes de resección, las complicaciones postoperatorias y la mortalidad.RESULTADOS:Se realizó resección multivisceral en 936 de 2242 pacientes, de los cuales 629 fueron sometidos a resección multivisceral extendida. La tasa de margen circunferencial positivo fue mayor después de la resección multivisceral que después de la escisión mesorrectal total: 21,2% versus a 13,9% (p <0,001). Se produjeron más complicaciones postoperatorias después de resecciones multiviscerales limitadas y extendidas en comparación con la escisión mesorrectal total (44,1% y 53,8% versus a 37,6%, p <0,001). La incidencia de mortalidad a 30 días fue igualmente baja en ambos grupos (1,5% versus a 2,2%, p = 0,20). Los predictores independientes de complicaciones posoperatorias fueron la edad ≥70 años (OR = 1,28, IC del 95% [1,04 a 1,56], p = 0,02), hombres (OR = 1,68, IC del 95% [1,38 a 2,04], p <0,001), tumores mucinosos (OR = 1,55, IC del 95% [1,06 a 2,27], p = 0,02), resección multivisceral extendida (OR = 1,98, IC del 95% [1,56 a 2,52], p <0,001), Hartmann (OR = 1,42, 95% Cl [1,07 a 1,90], p = 0,02) y resección abdominoperineal (OR 1,56, Cl 95% [1,25 a 1,96], p <0,001).LIMITACIONES:No se disponía de datos que especificaran el alcance de las resecciones multiviscerales y las complicaciones de Clavien Dindo I-II.CONCLUSIONES:Este estudio poblacional reveló tasas de complicaciones postoperatorias y positividad del margen circunferencial relativamente altas en pacientes con cáncer de recto cT4, especialmente después de resecciones multiviscerales, pero tasas de mortalidad bajas. Consulte Video Resumen en http://links.lww.com/DCR/B457.

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges.

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.

Use of treatment pathway improves neoadjuvant chemotherapy use in muscle-invasive bladder cancer.

PURPOSE: To assess the trends of neoadjuvant chemotherapy (NAC) use since its introduction in our practice pathway in patients with cT2 + bladder cancer over a 20-year period. METHODS: This is a retrospective review of patients with cT2 + bladder cancer who underwent RC between 01/01/1998 and 01/01/2018 that aimed to evaluate the trends of NAC use and associated after implementation of a multidisciplinary treatment pathway. Cohorts were stratified into eras: pre-NAC (1998-2007) to NAC eras (2008-2018). Univariate analysis was conducted using Chi-squared test and Kaplan-Meier estimates were used to evaluate survival. RESULTS: In 904 total patients who underwent RC, there were 493 with cT2 + UCC disease. The rate of NAC peaked at 84.2% in the most recent year of analysis in all patients and was 100% in cT2 + patients eligible for NAC. There was an increased rate of complete response (downstage to pT0) from 8.7% to 15.8% (p = 0.018) between the two eras. Unadjusted survival analysis revealed improved overall survival (OS) between eras with 5-year OS 53.2% vs. 42.7% and 10-year OS 42.7% vs. 26.4% in the NAC vs. pre-NAC cohorts, respectively (p = 0.016). CONCLUSIONS: In this review of 20 years of experience, we report a dramatic rise in the use of NAC after adoption of a multidisciplinary pathway that is associated with expected survival benefits.

Trends in the use of neoadjuvant chemotherapy and oncological outcomes for high-risk upper tract urothelial carcinoma: a multicentre retrospective study.

OBJECTIVE: To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS: Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. CONCLUSIONS: The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

A nine-lncRNA signature predicts distant relapse-free survival of HER2-negative breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy.

Multi-gene prognostic signatures of long non-coding RNAs (lncRNAs) provide new insights into mechanisms of HER2-negative breast cancer development and progression, and predict distant relapse-free survival (DRFS) of patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. The aim of this study was to develop such a multi-lncRNAs signature. Optimal multiple candidate signature lncRNAs associated with DRFS were firstly identified by a univariate Cox proportional hazard regression survival analysis and a robust likelihood-based survival analysis of the GEO dataset GSE25055. A nine-lncRNA prognostic risk score model Risk Score = 0.0289 × EXPLOC100507388 - 0.0814 × EXPLINC00094 - 0.2422 × EXPSMG7-AS1 - 0.2433 × EXPPP14571 + 0.4690 × EXPASAP1-IT1 - 0.2483 × EXPLOC103344931 - 0.2464 × EXPFAM182A + 0.3349 × EXPHCG26 - 0.0216 × EXPLINC00963 was built according to the coefficients of multivariate survival analysis of the association between the candidate lncRNAs and survival. EXPlncRNA was the standardized log2-transformed expression level of the gene. According to this model, higher scores predicted lower survival probability. The area under Receiver operating characteristic (ROC) curve (AUC) was 0.777 to 0.823 from 1- to 7- year survival rate. The model and its individual lncRNAs differentiated survival probability between the higher scores (expression) and the lower scores (expression). The nine-lncRNA signature had the robust prognostic power compared with ER, PR, tumor size (T), lymph node invasion (N), TNM stage, pathologic response, chemosensitivity prediction and PAM50 signature. These results were consistent with those based on the GEO dataset GSE25065. The predictive nomograms integrating both the nine-lncRNA signature classifier and clinical-pathological risk factors were robust in predicting 1-, 3- and 5- year survival probabilities. These results supported that the nine-lncRNA signature was a robust and effective model in predicting DRFS of patients with HER2-negative breast cancer following taxane and anthracycline-based neoadjuvant chemotherapy.

Current advancements and future perspectives of immunotherapy in colorectal cancer research.

5-Fluorouracil (5-FU) is the first-line chemotherapy drug for colorectal cancer but most of the patients get resistant to the drug on a longer course of treatment. After the successful use of immunotherapy in melanoma treatment, it was explored with enthusiasm in different types of solid cancers including colorectal cancer. Nivolumab and pembrolizumab (Programmed cell death-1 blocking antibodies) have shown efficacy in the mismatch repair deficient high microsatellite instability (dMMR-MSI-H) subtype of metastatic colorectal cancer (CRC) patients. Immunotherapy has shown long time remission in a subset of metastatic CRC patients. The molecular mechanism and emerging roles of immunotherapy in colorectal cancer are explored in this review article and future directions for the proper utilization of the development in immunobiology are suggested.

New trends in neoadjuvant therapy of locally advanced rectal cancer from a surgeons perspective - a commentary.

BACKGROUND: Rectal cancer treatment advanced rapidly during last decades. The most important factors of this progress are new neoadjuvant therapy options, improvement in imaging (allowing for quality staging and restaging) and routine implementation of the total mesorectal excision technique. For the best outcomes, it is crucial to combine the treatment methods in the best way possible with ideal timing. It is necessary to keep in mind both advantages and complications of the individual kinds of approach. Therefore, interdisciplinary agreement is essential in the treatment of rectal cancer. Considering these new therapeutic possibilities, the debate about timing, indication and radicality of the surgical procedures is reopened. Surgical approaches are currently focused on mini-invasive methods and robotic surgery. New trend with promising potential seems to be clinical complete response achievement with watch and wait follow-up strategy. This approach, in the spirit of the organ sparing philosophy, however asks new questions about indication, timing and conception of this method. Proper answers are essential for sparing, yet radical oncotherapy of this disease.

Trends in utilization of neoadjuvant and adjuvant chemotherapy for muscle invasive bladder cancer.

PURPOSE: Previous studies have noted increased utilization of perioperative chemotherapy over time. The goal of this study was to determine trends in perioperative chemotherapy use within a contemporary population. MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with cT2-4N0M0 urothelial muscle invasive bladder cancer from 2011 to 2015 and underwent subsequent radical cystectomy. We retrospectively analyzed factors associated with perioperative chemotherapy and evaluated overall treatment trends in the use of neoadjuvant and adjuvant chemotherapy. Linear regression, logistic regression, Cox regression, and Kaplan-Meier analysis were performed. RESULTS: In total, 7,101 patients met inclusion criteria for analysis. The use of perioperative chemotherapy increased from 46.4% in 2011 to 57.2% in 2015 (p=0.003). Neoadjuvant chemotherapy use increased from 22.9% to 32.3% (p=0.007) over the time period analyzed, while adjuvant chemotherapy use experienced no significant change (23.5% to 24.9%, p=0.182). Logistic regression demonstrated that increased age and Charlson Comorbidity Index were predictors of not receiving chemotherapy (p<0.05), while those with increasing T stage, income above $48,000, and insurance other than Medicaid or Medicare were more likely to receive perioperative chemotherapy (p<0.05). Kaplan-Meier analysis revealed patients receiving neoadjuvant chemotherapy had the best 5-year overall survival at 48.3% compared to adjuvant chemotherapy (42.6%) or no chemotherapy (37.8%) (p<0.001). CONCLUSIONS: The increasing use of perioperative chemotherapy noted in prior studies has continued through 2015. Neoadjuvant chemotherapy appears to drive this increase while adjuvant chemotherapy utilization remains unchanged. Clinical and socioeconomic factors affect utilization of perioperative chemotherapy.

[Advances in perioperative systemic therapy for hepatocellular carcinoma].

The low surgical resection rate and high postoperative recurrence rate of hepatocellular carcinoma(HCC) are urgent clinical problems to be solved. Therefore, it is important to develop effective perioperative treatment. In recent years, a growing number of studies have shown that systemic therapy is expected to break through the limitations of traditional local treatment and play an important role in preoperative treatment. For example, some novel targeted agents and immunocheckpoint inhibitors have shown excellent potential as neoadjuvant treatment for HCC. Meanwhile, researchers have explored the application of systemic therapy as adjuvant therapy, but due to different criteria for patient selection, no consensus is reached on its efficacy. By far, there is no standard procedure for the application of systemic therapy in HCC perioperative period, little is known about the efficacy and safety of targeted drugs and immunotherapy. This article discusses the feasibility of systemic therapy as neoadjuvant and adjuvant treatment of HCC, as well as its adverse events, with an aim to provide new horizons of HCC systemic therapy in the perioperative period.