Adjuvant Cancer Treatment Research Articles

PO-1339 Long- term outcomes after electronic brachytherapy in the adjuvant treatment of endometrial cancer.

PO-1339 Long- term outcomes after electronic brachytherapy in the adjuvant treatment of endometrial cancer.

Adjuvant treatment in early-stage endometrial cancer: context-dependent impact of somatic CTNNB1 mutation on recurrence-free survival

ObjectiveThe primary objective of this study was to determine whether women whose tumors harbor a somatic CTNNB1 mutation have longer recurrence-free survival if they receive traditional adjuvant therapy strategies compared...

The role of physical activity against chemotherapy-induced peripheral neuropathy: a narrative review

Several studies investigated the side effect of adjuvant cancer treatments, and different types of preventive techniques or treatments have been assessed. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological side effect. Exercise training has been widely studied as an adjuvant therapy to prevent CIPN and improve post-chemotherapy functional outcome and quality of life (QoL). This narrative review aims to summarize the data obtained from the latest studies about physical activity (PA) for the prevention and treatment of CIPN and associated QoL measures. Literature research was conducted to obtain studies including PA interventions for patients with CIPN. Ten studies met inclusion criteria and were therefore summarized and discussed, focusing on exercise type and functional outcome. It seems clear that, regardless of the type of exercise, PA plays a positive role in the treatment of CIPN, providing a significant symptom improvement. There has been no standardization of type, quantity, and intensity of PA administered to the subjects in the various studies probably due to a physiological difference between samples, grade of neuropathy, and difference among therapies.

Field Safety Experience With an Autologous Cancer Vaccine in 41 Horses: A Retrospective Study (2019–2021)

Autologous cancer vaccines (ACV) are an emerging option for adjuvant cancer treatment in veterinary medicine. With this form of active immunotherapy, the patient's tumor cells are processed ex vivo and returned to the patient with the goal of stimulating an immune response to unique, patient-specific antigens. The case accession database at Torigen was queried to identify horses that underwent biopsy or surgical resection of their primary tumor and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. The records were then reviewed for any reported adverse events (AE). Forty-one horses met the inclusion criteria and received 252 doses of Torigen's ACV (ACV-T). There were seven AEs reported in four horses, which were associated with 1.6% of the administered doses of the ACV-T. Of the reported AE, all were characterized as mild. The ACV-T appears to be well tolerated by horses, and may be useful as a treatment option for owners who are concerned about AEs that can occur with other types of adjuvant cancer therapy. Additional studies are warranted to evaluate the efficacy of this ACV in horses with solid tumors.

Immunotherapy in Gastro-Oesophageal Cancer: Current Practice and the Future of Personalised Therapy.

Initial studies of immune checkpoint inhibitors in biomarker unselected gastro-oesophageal cancer yielded limited improvement in survival. However, emerging data from recent clinical trials suggest immunotherapies may offer a meaningful clinical benefit within selected populations. Gastro-oesophageal cancer is a heterogeneous disease with respect to histopathological and molecular features; hypermutation and the biology of immune checkpoint pathways are key to appropriate selection of populations most likely to benefit from immune checkpoint inhibitors. Programmed death-ligand 1 expression, typically measured using the combined positive score, is an important biomarker in determining which patients may benefit from immunotherapy agents. However, combined positive score thresholds are not standardised across trials and the benefit in programmed death-ligand 1-negative cohorts is uncertain. Data suggest that patients with tumours with microsatellite instability, high tumour mutational burden and Epstein-Barr Virus positivity are more likely to benefit from immunotherapy, which may be of importance within programmed death-ligand 1-negative populations. Here, we describe the current evidence base for the use of checkpoint inhibitors in the treatment of advanced gastro-oesophageal cancer and adjuvant treatment of high-risk oesophageal cancer, as well as the ongoing studies of immunotherapy in the treatment of patients with gastro-oesophageal cancers across an increasing range of clinical settings.

Future concepts for neoadjuvant and adjuvant treatment of (resectable) pancreatic cancer

Pancreatic cancer still has a very unfavorable prognosis. This is true even for the comparably small group of patients (maximum 15%) who are diagnosed with a clearly resectable tumor. The article provides information on the current statements of the S3 guidelines on adjuvant and neoadjuvant treatment of resectable pancreatic cancer and describes adjuvant and neoadjuvant treatment strategies. Furthermore, the article pursues the questions of if and for whom a total neoadjuvant treatment is suitable and which options of a personalized treatment are available for resectable pancreatic cancer.

Updates in the Adjuvant Treatment of Non-Small Cell Lung Cancer

Over the past decade there has been significant advancement in the systemic therapy of non-small cell lung cancer, especially in the metastatic setting. More recently, medications which have been proven in advanced disease have been shown to provide benefit in the adjuvant setting as well. We review two recent trials which have studied the use of EGFR-targeted therapies and checkpoint inhibitor therapies in patients who have undergone surgical therapy for resectable disease.

A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with a limited response to current therapies. Novel and effective treatment is urgently needed. Herein, a chimeric antigen receptor (CAR)-NK92 cell line, with an interleukin (IL)-15Rα-sushi/IL-15 complex and a Programmed cell death-1(PD1) signal inverter was constructed and named SP ( S ushi-IL15- P D1). We showed that CAR expression enabled SP cells to proliferate independently of IL-2 and became more resistant to nutrition starvation-induced apoptosis. Meanwhile, SP cells were more effective than NK92 in PDAC cell killing assays in vitro and in vivo, and there was a positive correlation between the killing capability of SP cells and PD-L1 expression in pancreatic cancer cells. Based on the synergistic and comprehensive effects of the special CAR structure, the adhesion, responsiveness, degranulation efficiency, targeted delivery of cytotoxic granule content, and cytotoxicity of SP cells were significantly stronger than those of NK92. In conclusion, the SP cell line is a promising adoptive immunotherapy cell line and has potential value as an adjuvant treatment for pancreatic cancer, especially in patients with high PD-L1 expression.

Nuciferine Inhibits TMEM16A in Dietary Adjuvant Therapy for Lung Cancer.

Lung cancer is a malignant tumor with the highest morbidity and mortality rates. Food therapy is a common adjuvant treatment for lung cancer due to its safety and painlessness. Developing new functional food and exploring novel drug targets is important for lung cancer adjuvant therapy. This study confirmed that the active ingredient nuciferine of the lotus leaf was a novel TMEM16A inhibitor by whole-cell patch clamp experiments and site-directed mutagenesis experiments. CCK8 assay, colony formation assay, wound healing assay, and Annexin-V assay were combined to prove that nuciferine inhibited the proliferation and migration of lung cancer cells and promoted cancer cell apoptosis by targeting TMEM16A. Moreover, the combination of nuciferine and cisplatin significantly enhanced the anti-cancer effect of cisplatin. In addition, the signal transduction pathway of nuciferine regulating LA795 cell proliferation, migration, and apoptosis was confirmed by western blot experiments. In vivo experiments showed that nuciferine was a safe and effective natural anti-cancer product for lung cancer. Tissue section pathological detection and pharmacokinetic experiments verified that intragastric administration of nuciferine significantly enhanced the cancer therapy effect of cisplatin and counteracted the toxicity of high concentrations of cisplatin. Therefore, nuciferine is an ideal functional food for adjuvant lung cancer treatment.

Dexamethasone promotes breast cancer stem cells in obese and not lean mice.

Obesity is highly prevalent in breast cancer patients and is associated with increased recurrence and breast cancer‐specific mortality. Glucocorticoids (GC) are used as an adjuvant in cancer treatment and are associated with promoting breast cancer metastasis through activation of stemness‐related pathways. Therefore, we utilized the synergetic allograft E0771 breast cancer model to investigate if treatment with GCs had differential effects on promoting cancer stem cells in lean and diet‐induced obese mice. Indeed, both lean mice treated with dexamethasone and obese mice with no treatment had no effect on the ex vivo colony‐forming ability, mammosphere formation, or aldehyde dehydrogenase (ALDH) bright subpopulation. However, treatment of obese mice with dexamethasone resulted in a significant increase in ex vivo colony formation, mammosphere formation, ALDH bright subpopulation, and expression of pluripotency transcription factors. GC transcriptionally regulated genes were not altered in the dexamethasone‐treated groups compared to treatment controls. In summary, these results provide initial evidence that obesity presents a higher risk of GC‐induced cancer stemness via non‐genomic GC signaling which is of potential translational significance.

Trends in surgery and adjuvant treatment for early-stage breast cancer: a population-based study in Queensland, Australia.

Our aim was to describe variations in the treatment of early-stage breast cancer and to examine factors associated with disease-specific survival (DSS). The study used linked data for 24,190 women with a T1 (≤ 20mm) breast cancer who underwent surgery from 2005 to 2019. Multivariate logistic regression was used to model predictors of receiving breast-conserving surgery (BCS) compared to mastectomy and a multinomial model was used to examine factors associated with type(s) of treatment received. Overall, 70.3% had BCS, with a reduced likelihood of BCS observed for younger women (p < 0.001), rural residence, (p < 0.001), socioeconomic disadvantage (p = 0.004), higher tumour grade (p < 0.001) and surgery in a public versus private hospital (p < 0.001). Compared to women who received BCS and radiation therapy (RT), those having mastectomy alone or mastectomy plus RT were more likely to be younger (p < 0.001), live in a rural area (p < 0.001), have higher-grade tumours (p < 0.001) and positive lymph nodes (p < 0.001). Overall 5-year survival was 95.3% and breast cancer-specific survival was 98.3%. Highest survival was observed for women having BCS and RT and lowest for those having mastectomy and RT (p < 0.001). Our results indicate some variation in the management of early-stage breast cancer. Lower rates of BCS were observed for rural and disadvantaged women and for those treated in a public or low-volume hospital. Whilst survival was high for this cohort, differences in tumour biology likely explain the differences in survival according to treatment type.

The Impact of Surgical Treatment with Adjuvant Chemotherapy for Ovarian Cancer on Disorders in the Urinary System and Quality of Life in Women.

Ovarian cancer is the fourth-most-common cause of death among all malignant cancers in women in Poland. This study aimed to compare the functioning of the urinary system and quality of life in women in the 12-month period following the completion of surgery or adjuvant treatment for ovarian cancer, with patients who underwent a hysterectomy for non-oncological reasons (control group). The study group consisted of 50 patients diagnosed with stage I–III ovarian cancer. Among 38 patients with type II ovarian cancer (group A), surgery followed by first-line chemotherapy was performed. Within this group of patients, 20 had stage I ovarian cancer, while 18 had stage II ovarian cancer. The study was performed at least 6 months after the final chemotherapy cycle, with no clinical, marker or radiological recurrence determined. On the other hand, in 12 patients with stage I type I ovarian cancer, oncological treatment consisted of only surgery, without the need for adjuvant chemotherapy, due to the low stage of the lesions (group B). In turn, the control group consisted of 50 women who underwent uterine removal for non-oncological reasons (group C). The assessment of quality of life was conducted using the questionnaires: Satisfaction with Life Scale (SWLS); Incontinence Impact Questionnaire, short form (IIQ-7); Urogenital Distress Inventory (UDI-6); and the Sexual Satisfaction Scale for 3, 6, 9, and 12 months after the conclusion of oncological treatment. During the follow-up, a significant reduction in the quality of everyday life and sexual life was noted among patients with ovarian cancer, more pronounced in group B, compared to the control group (p < 0.05). The risk of urinary incontinence is independent of the treatment regimen chosen for ovarian cancer. It is necessary to consider comprehensive psychological care and sexual therapy in patients with ovarian cancer and their families.

Current Perspectives on the Importance of Pathological Features in Prognostication and Guidance of Adjuvant Chemotherapy in Colon Cancer.

There is not a clear consensus on which pathological features and biomarkers are important in guiding prognosis and adjuvant therapy in colon cancer. The Pathology in Colon Cancer, Prognosis and Uptake of Adjuvant Therapy (PiCC UP) Australia and New Zealand questionnaire was distributed to colorectal surgeons, medical oncologists and pathologists after institutional board approval. The aim of this study was to understand current specialist attitudes towards pathological features in the prognostication of colon cancer and adjuvant therapy in stage II disease. A 5-scale Likert score was used to assess attitudes towards 23 pathological features for prognosis and 18 features for adjuvant therapy. Data were analysed using a rating scale and graded response model in item response theory (IRT) on STATA (Stata MP, version 15; StataCorp LP). One hundred and sixty-four specialists (45 oncologists, 86 surgeons and 33 pathologists) participated. Based on IRT modelling, the most important pathological features for prognosis in colon cancer were distant metastases, lymph node metastases and liver metastases. Other features seen as important were tumour rupture, involved margin, radial margin, CRM, lymphovascular invasion and grade of differentiation. Size of tumour, location, lymph node ratio and EGFR status were considered less important. The most important features in decision making for adjuvant therapy in stage II colon cancer were tumour rupture, lymphovascular invasion and microsatellite instability. BRAF status, size of tumour, location, tumour budding and tumour infiltrating lymphocytes were factored as lesser importance. Biomarkers such as CDX2, EGFR, KRAS and BRAF status present areas for further research to improve precision oncology. This study provides the most current status on the importance of pathological features in prognostication and recommendations for adjuvant therapy in Australia and New Zealand. Results of this nationwide study may be useful to help in guiding prognosis and adjuvant treatment in colon cancer.

Abstract P2-13-37: A prospective, open, multi-center clinical study of pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvant treatment for stage II-III HER2-positive breast cancer patients

Abstract Background: Targeted therapy has significant efficacy in adjuvant and advanced treatment of HER2-positive breast cancer, and it has also promoted its development in neoadjuvant therapy. For HER2-positive breast cancer, chemotherapy with anthracyclines and taxanes combined with trastuzumab targeted therapy is currently the standard regimen for adjuvant or neoadjuvant therapy. On the basis of the preliminary clinical trials, we carried out this study to confirmed efficacy and safety of pyrotinib combined with trastuzumab and nab-paclitaxel as neoadjuvant treatment regimen in patients(pts) with stage II- III HER2-positive breast cancer. Method: In this multicenter, single arm, prospective, open-label phase II study, 46pts with stage II-III HER2-positive breast cancer will be enrolled (in Simon twostages model, 16 pts will be enrolled in the first stage) to receive pyrotinibcombined with trastuzumab and nab-paclitaxel. The inclusion criteria are asflows. (1) female aging from 18 to 75; (2) Eastern Cooperative Oncology Group(ECOG) performance score of 0-1; (3) Life expectancy is no less than 12weeks;(4) Pathologically confirmed HER-2 positive breast cancer;(5) earlystage (T2-3, N0-1, M0) or locally advanced (T2-4, N2, or N3), with tumor sizeno less than 2cm in diameter. All pts will receive pyrotinib (400mg qd) andtrastuzumab: 8 mg/kg for cycle 1 and 6 mg/kg for cycles 2-6, intravenousinfusion, 21 days for 1 cycle, a total of 6 cycles and nab-paclitaxel: 260mg/m2,intravenous infusion, 21 days as a cycle, a total of 6 cycles. The primaryendpoint is pathological complete response rate (pCR: ypT0/is, ypN0), and thesecondary endpoints are disease-free survival time (DFS), objective responserate (ORR), and survival time without distant metastasis (DDFS). Findings: From Nov 2020 to May 2021, a total of 11 pts were enrolled, 4 pts havecompleted surgery and 6 pts could be evaluated for ORR. The pCR rate was50%, ORR was 100% (5 PR, 1CR). Adverse events (AEs) of any garde werediarrhea 11 (100.0%), anorexia and vomiting 8 (72.7%) and rash 4 (36.4%).Garde 3 AEs were diarrhea 3 (27.3%), and there was no grade 4 AEs. Conclusion: Pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvanttreatment for pts with stage II-III HER2-positive breast cancer showedacceptable toxicity and promising efficacy. Citation Format: Bin Shao, Zhengyan Yu, Yu Wang, Guangcai Zhao, Fei Zhou, Ranmei Wei. A prospective, open, multi-center clinical study of pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvant treatment for stage II-III HER2-positive breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-37.

Effects of Lactobacillus acidophilus KLDS1.0901 on Proliferation and Apoptosis of Colon Cancer Cells.

Colon cancer is the most common type of malignant tumor. The cytotoxicity effect of lactic acid bacteria may be active by inhibiting cancer cell proliferation, producing anticancer compounds, and inducing apoptosis in cancer cells, but the mechanism is unclear. Our previous study revealed that Lactobacillus acidophilus KLDS1.0901 has good probiotic properties. In this study, We screened out the highest inhibition rate of L. acidophilus KLDS1.0901 and assessed the effects on the proliferation of HT-29, Caco-2, and IEC-6 cells. Then, the apoptosis mechanism of HT-29 cells was studied when treated with L. acidophilus KLDS1.0901. Results showed that L. acidophilus KLDS1.0901 inhibited the proliferation of HT-29 and Caco-2 cells in a dose-dependent manner and reached the maximum under the condition of multiplicity of infection (MOI) = 100 (rate of Lactobacillus to cells) at 48 h. With the increase in time and MOI, reactive oxygen species in HT-29 cells, the apoptosis rates of HT-29 cells were increased, and the amount of blue fluorescence of the cells was also increased after Hoechst 33258 staining. Furthermore, L. acidophilus KLDS1.0901 reduced the mitochondrial membrane potential of HT-29 cells. Notably, 1,133 differentially expressed genes were screened by transcriptomics research, including 531 up-regulated genes and 602 down-regulated genes. These genes were involved in the nuclear factor κB and PI3K-AKT signaling pathways related to the apoptosis of HT-29 cells. These findings suggested that L. acidophilus KLDS1.0901 has the potential to be used in the development of a new type of functional foods for adjuvant treatment of colon cancer.

Report from 'ESCP 2021 Virtual': the 16th Scientific and Annual Conference of the European Society of Coloproctology, 22-24 September 2021.

Report from 'ESCP 2021 Virtual': the 16th Scientific and Annual Conference of the European Society of Coloproctology, 22-24 September 2021.

\u201cMYH9 mutation and squamous cell cancer of the tongue in a young adult: a novel case report\u201d

BackgroundThe incidence of tongue cancer in young adults is on the rise. This trend is more pronounced in females. Although the aetiology is still unclear, there is mounting evidence that genetic syndromes can play a key role in development of oral cancers in this patient group. We report the first case of oral squamous cell carcinoma (oSCC) in a young adult with an MYH9-related disorder (MYH9-RD).Case presentationA 19-year-old female with a germline MYH9 variant (missense variant in exon 2: c.287C > T, (p.Ser96Leu)) was referred to the head and neck surgery department for investigation of a painful, thick right tongue ulcer. She was diagnosed with Epstein syndrome, an MYH9-RD, at 12 years of age. Her main phenotypic features were profound thrombocytopenia and marked renal impairment. The tongue biopsy confirmed SCC. Preoperative positron emission tomography (PET) revealed avidity in the right tongue and ipsilateral level 2A neck lymph node. With substantial preoperative multidisciplinary input, she underwent cancer ablation and microvascular free flap reconstruction. Her pathology showed a 35 mm diameter, 14 mm thick moderately differentiated SCC with perineural and lymphovascular invasion. Two out of 38 right neck nodes were positive for metastasis with extranodal extension. None of the 34 left neck nodes was involved.She had an uneventful recovery and was discharged home on day 6 postoperative day. On day 15 postoperative day, she had catastrophic bleeding in the neck with a respiratory arrest after a forceful cough. She required an emergency tracheostomy and returned to the theatre for haemostasis. Following a short inpatient stay, she was again discharged home and underwent adjuvant therapy consisting of external beam radiotherapy of 60Gy in 30 fractions. On clinical examination and PET at 6 months after surgery, she had no evidence of disease recurrence.ConclusionsMYH9-RD can present with advanced locoregional oral cavity malignancy at an early age. The combination of profound thrombocytopenia and marked renal impairment can impact heavily on routine major head and neck cancer surgery and adjuvant treatment. This rare and challenging condition underlines the importance of early detection of cancer and multidisciplinary team input.

Identification of AHSA1 as a Potential Therapeutic Target for Breast Cancer: Bioinformatics Analysis and in vitro Studies.

Shenling Baizhu Powder (SBP), a famous Traditional Chinese Medicine (TCM) formulation, has been widely used in the adjuvant treatment of cancers, including breast cancer. This study aims to identify potential new targets for breast cancer treatment based on the network pharmacology of SBP. By analyzing the relationship between herbs and target proteins, potential targets of multiple herbs in SBP were identified by network pharmacology analysis. Besides, by comparing the data of breast cancer tissue with normal tissue, upregulated genes in two breast cancer expression profiles were found. Thereafter, the expression level and prognosis of activator of heat shock protein 90 (HSP90) ATPase activity 1 (AHSA1) were further analyzed in breast cancer by bioinformatics analysis, and the network module of AHSA1 binding protein was constructed. Furthermore, the effect of knocking down AHSA1 on the proliferation, migration, and invasion of breast cancer cells was verified by MTT, clone formation assay, and transwell assay. Vascular endothelial growth factor A (VEGFA), intercellular adhesion molecule 1 (ICAM1), chemokine (C-X-C motif) ligand 8 (CXCL8), AHSA1, and serpin family E member 1 (SERPINE1) were associated with multiple herbs in SBP. AHSA1 was remarkably upregulated in breast cancer tissues and positively correlated with poor overall survival and disease metastasis- free survival. Furthermore, knockdown of AHSA1 significantly inhibited the migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells but had no obvious effect on proliferation. In addition, among the proteins that bind to AHSAl, the network composed of proteasome, chaperonin, and heat shock proteins is closely connected, and these proteins are associated with poor prognosis in a variety of cancers. AHSA1 is positively correlated with breast cancer progression and might act as a novel therapeutic target for breast cancer.

A twice-daily or a three-times-daily tegafur-uracil and leucovorin calcium regimen as adjuvant therapy in patients with resected colorectal cancer: A phase III study.

38 Background: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The schedule of 28-day oral administration followed by a 7-day rest period was repeated. Five 35-day cycles were repeated. The primary endpoint was 3-year disease-free survival. The secondary endpoints included 5-year overall survival and toxicity. Results: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The 5-year overall survival rates of group A and B were 89.7% and 91.0% (95% confidence interval, 83.3-92.8-84.8-93.8), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusions: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase. Clinical trial information: UMIN000005594.

Oncological outcomes of concomitant carcinoma in situ at radical cystectomy in pure urothelial bladder cancer and in histological variants.

The presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants. We evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage. Median age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease). Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomy Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants. Concomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.