Intensive Surveillance Protocol Research Articles

Cardiological parameters predict mortality and cardiotoxicity in oncological patients.

Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient-related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all-cause mortality (ACM) and the development of cardiotoxicity. Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio-Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12-lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs-cTnT of ≥ 7ng/L [odds ratio (OR) 1.82, P<0.001] and NT-proBNP (OR 1.98, P<0.001) were independent predictors of ACM, while reduced left ventricular ejection fraction was not associated with increased ACM (P=0.85). The secondary endpoint was reached by 182 patients (9.2%) with a median of 793.5 [IQR 411.2, 1165.0] days. Patients with multiple CVRFs (defined as high risk, n=886) had an increased risk of cardiotoxicity (n=100/886, 11.3%; hazard ratio 1.57, P=0.004). They showed elevated baseline values of hs-cTnT (OR 1.60, P=0.006) and NT-proBNP (OR 4.00, P<0.001) and had an increased risk of ACM (OR 1.43, P=0.031). In cancer patients, CVRF accumulation predicts cardiotoxicity whereas elevated hs-cTnT or NT-proBNP levels are associated with ACM. Accordingly, less intensive surveillance protocols may be warranted in patients with low cardiac biomarker levels and absence of CVRFs.

Early Cancer Detection in Li-Fraumeni Syndrome with Cell-Free DNA.

By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients. See related commentary by Latham et al., p. 23. This article is featured in Selected Articles from This Issue, p. 5.

Patterns of recurrent disease after neoadjuvant chemoradiotherapy and esophageal cancer surgery with curative intent in a tertiary referral center

BackgroundRecurrence is frequently observed after esophageal cancer surgery, with dismal post-recurrence survival. Neoadjuvant chemoradiotherapy followed by esophagectomy is the gold standard for resectable esophageal tumors in the Netherlands. This study investigated the recurrence patterns and survival after multimodal therapy. MethodsThis retrospective cohort study included patients with recurrent disease after neoadjuvant chemoradiotherapy followed by esophagectomy for an esophageal adenocarcinoma in the Amsterdam UMC between 01 and 01–2010 and 31-12-2018. Post-recurrence treatment and survival of patients were investigated and grouped by recurrence site (loco-regional, distant, or combined loco-regional and distant). ResultsIn total, 278 of 618 patients (45.0%) developed recurrent disease after a median of 49 weeks. Thirty-one patients had loco-regional (11.2%), 145 distant (52.2%), and 101 combined loco-regional and distant recurrences (36.3%). Post-recurrence survival was superior for patients with loco-regional recurrences (33 weeks, 95%CI 7.3–58.7) compared to distant (12 weeks, 95%CI 6.9–17.1) or combined loco-regional and distant recurrent disease (18 weeks, 95%CI 9.3–26.7). Patients with loco-regional recurrences treated with curative intent had the longest survival (87 weeks, 95%CI 6.9–167.4). ConclusionRecurrent disease after potentially curative treatment for esophageal cancer was most frequently located distantly, with dismal prognosis. A subgroup of patients with loco-regional recurrence was treated with curative intent and had prolonged survival. These patients may benefit from intensive surveillance protocols, and more research is needed to identify these patients.

Is a less-intensive follow-up for colon cancer in early stages reasonable?

PurposePatients with colon cancer are usually included in an intensive 5-year surveillance protocol after curative resection, independent of the tumor stage, though early stages have a considerably lower risk of recurrence. The aim of this study was to analyze the adherence to an intensive follow-up and the risk of recurrence in patients with colon cancer in UICC stages I and II.MethodsIn this retrospective study, we assessed patients who underwent resection for colon cancer in UICC stages I and II between 2007 and 2016. Data were collected on demographics, tumor stages, therapy, surveillance, recurrent disease, and oncological outcome.ResultsOf the 232 included patients, 43.5% (n = 101) reached the 5-year follow-up disease-free. Seven (7.5%) patients in stage UICC I and sixteen (11.5%) in UICC II had a recurrence, with the highest risk in patients with pT4 (26.3%). A metachronous colon cancer was detected in four patients (1.7%). The therapy of recurrence was intended to be curative in 57.1% (n = 4) of UICC stage I and in 43.8% (n = 7) of UICC stage II, but only in one of seven patients over 80 years. 44.8% (n = 104) of the patients were lost to follow-up.ConclusionA postoperative surveillance in patients with colon cancer is important and recommended as a recurrent disease can be treated successfully in many patients. However, we suggest that a less intensive surveillance protocol is reasonable for patients with colon cancer in early tumor stages, especially in UICC stage I, as the risk of recurrent disease is low. With elderly and/or frail patients in a reduced general condition, who will not endure further specific therapy in case of a recurrence, the performance of the surveillance should be discussed: we recommend a significant reduction or even renunciation.

Watch and Wait in Rectal Cancer After a Complete Response to Chemoradiotherapy – Is It Safe and Are We Doing Enough?

AimsTo summarise current understanding and the associated outcomes of the watch and wait approach after a clinical complete response (cCR) of rectal cancer to chemoradiotherapy. Materials and methodsA contemporary and comprehensive literature review was carried out using focused searches of the MEDLINE and Google Scholar databases. ResultsThe watch and wait approach is now an established and oncologically safe option for patients who develop a cCR. Long-term survival is equivalent to primary rectal resection and quality of life outcomes are demonstrably superior. The tumour regrowth rate of 25–33% is higher than local recurrence rates after total mesenteric excision. Therefore, intensive surveillance protocols are required to enable early salvage surgery. Salvage is feasible in more than 84% of cases, with equivalent survival outcomes to primary resection. DiscussionCurrent evidence focuses on patients with locally advanced disease, but there are superior rates of cCR and organ preservation in earlier stages of rectal cancer. A shift towards planning for cCR and maximising cCR rates is the logical next step for rectal preservation. Emerging evidence attempts to predict those who will achieve a complete response and allow more tailored management plans, and earlier cancers may represent the optimal targets.

Reassessment of intensive surveillance practices adopted for endometrial cancer survivors

BackgroundIn Japan, 17,000 women are newly diagnosed with endometrial cancer in 2018. The healthcare insurance policy in Japan provides more intensive patient surveillance compared with the United States and European countries. The aim of this study was to retrospectively analyze data, including surveillance methods, recurrence sites, salvage therapy, and survival period after recurrence, to consider the benefits of surveillance for patients with endometrial cancer.MethodsBetween January 2009 and December 2015, the medical records of patients who were initially diagnosed with the International Federation of Gynecology and Obstetrics stage I–IV endometrial cancer and treated were enrolled in this retrospective study. Only patients with stage IV cancer with peritoneal dissemination were included. Within the first 2 years, the included patients underwent tumor marker tests, Papanicolaou smear test every 1–3-months, and imaging analysis at 6–12- month intervals. Until 4 years, the patients underwent regular surveys every 4 months and imaging analysis annually. Subsequently, the patients received regular surveys every 6 -to 12-months. Results.Among 847 patients, 88 experienced recurrence, and their clinicopathological data were statistically analyzed. The recurrence site was not associated with the initial treatment method or histology. Among the patients with recurrence, 75% were asymptomatic. Univariate analysis demonstrated that time to recurrence and local recurrence were significant factors for survival outcomes, whereas multivariate analysis indicated that only local recurrence was a significant factor. In patients with distant metastasis, neither symptomatic nor asymptomatic recurrence showed a significant difference in survival.ConclusionsIn this retrospective study, an intensive surveillance protocol did not benefit patients with endometrial cancer. Thus, we hypothesize that the characterization of tumors by emerging technologies that can precisely predict the nature of the tumor will help tailor individualized and efficient surveillance programs. In addition, the ideal salvage therapy needs to be developed to benefit patients after recurrence.

Outcomes of rectal cancer patients with a positive pathological circumferential resection margin.

Evidence-based management of positive pathological circumferential resection margin (pCRM) following preoperative radiation and an adequate rectal resection for rectal cancers is lacking. Retrospective analysis of prospectively maintained single-centre institutional database was done to study the patterns of failure and management strategies after a rectal cancer surgery with a positive pCRM. A total of 86 patients with rectal adenocarcinoma with a positive pCRM were identified over 8years (2011-2018). Majority had low-lying rectal cancers (90.7%) and were operated after preoperative radiotherapy (95.3%). Operative procedures included abdomino-perineal resections, inter-sphincteric resections, low anterior resections and pelvic exenteration in 61 (70.9%), 9 (10.5%), 11(12.8%) and 5 (5.8%) patients respectively. A total of 83 (96.5%) received chemotherapy as the sole adjuvant treatment modality while 2 patients (2.3%) were given post-operative radiotherapy and 1 patient underwent revision surgery. A total of 53 patients (61.6%) had recurrence, with 16 (18.6%), 20 (23.2%), 8(9.3%) and 9 (10.5%) patients having locoregional, systemic, peritoneal and simultaneous local-systemic relapse. Systemic recurrences were more often detected either by surveillance in an asymptomatic patient (20.1%) while local (13.1%) and peritoneal (13.2%) recurrences were more often symptomatic (p = 0.000). The 2-year overall survival (OS) and disease-free survival (DFS) of the cohort was 82.4% and 74.0%. Median local recurrence-free survival (LRFS) was 10.3months. Patients with a positive pCRM have high local and distal relapse rates. Systemic relapses are more often asymptomatic as compared to peritoneal or locoregional relapse and detected on follow-up surveillance. Hence, identification of such recurrences while still salvageable via an intensive surveillance protocol is desirable.

627 PL11.02 ENSURE: AN INTERNATIONAL MULTICENTRE STUDY EXPLORING WHETHER SURVEILLANCE AFTER ESOPHAGEAL CANCER SURGERY IMPACTS ONCOLOGICAL AND QUALITY OF LIFE OUTCOMES

Abstract Although established and emerging therapies for recurrent esophageal cancer (EC) may impact on survival and health related quality of life (HR-QL), surveillance protocols after the primary curative treatment of EC are varied and inconsistent, reflecting a limited evidence-base to guide an optimum approach. Specifically, whether advantages exist for an intensive surveillance protocol is unknown and was the focus of this study. Methods ENSURE was an international multicentre observational study of consecutive patients undergoing surgery with curative intent for esophageal and junctional cancers (2009–2015) across 20 European and North American centers (NCT03461341). Intensive surveillance (IS) was defined as routine annual CT/PET-CT during the first three postoperative years, and compared with standard surveillance (SS) with investigation as clinically indicated. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival (DSS), disease-free survival (DFS), recurrence pattern, and HR-QL. Multivariable linear, logistic and Cox proportional hazards regression analyses were performed to determine the independent impact of surveillance on oncologic outcomes and HR-QL. Results 4,682 patients were studied, 45.5% underwent IS. At median follow-up of 60 months, 47.5% developed recurrence; oligometastatic in 39% of cases, with 31% receiving best supportive care, 60% chemotherapy and/or radiation, and 8% surgical resection. IS was associated with reduced symptomatic recurrence (OR0.17 [0.12–0.25]), increased tumor-directed therapy (OR2.09 [1.58–2.77]), and improved OS (HR0.90 [0.82–0.98], 5-year OS 47.9 ± 1.2% versus 43.2 ± 1.1%). On multivariable analysis, significantly improved OS with IS was maintained for patients who underwent surgery alone (HR0.60 [0.47–0.78]) and in those with lower pathological (y)pT stages (Tis-2, HR0.72 [0.58–0.89]). IS was associated with greater anxiety (P = 0.016), but similar overall HR-QL. Conclusion These data suggest that IS may improve oncologic outcomes, particularly in patients with early stage disease at presentation or with a favorable pathological stage post induction therapy. This may be relevant to guideline development and provide a framework and rationale for RCTs. It may also inform shared decision-making with patients at a time where therapeutic options for recurrence are expanding.

ENSURE: An international multicenter study exploring whether surveillance after esophageal cancer surgery impacts oncological and quality-of-life outcomes.

4032 Background: Although established and emerging therapies for recurrent esophageal cancer (EC) may impact on survival and health related quality of life (HRQL), surveillance protocols after the primary curative treatment of EC are varied and inconsistent, reflecting a limited evidence-base to guide an optimum approach. Specifically, whether advantages exist for an intensive surveillance protocol is unknown and was the focus of this study. Methods: European iNvestigation of SUrveillance after Resection for Esophageal cancer (ENSURE) is an international multicenter retrospective observational study of consecutive patients undergoing surgery with curative intent for esophageal and gastroesophageal junction cancers (2009 – 2015) across 20 European and North American cancer centers (NCT03461341). Intensive surveillance (IS) was defined as routine annual CT/PET-CT along with clinical assessment during the first three postoperative years, and compared with standard surveillance (SS) with investigation as clinically indicated. The primary outcome measure was overall survival (OS), secondary outcomes included treatment administered, disease-specific survival (DSS), disease-free survival (DFS), recurrence pattern, and HRQL. Multivariable linear, logistic and Cox proportional hazards regression analyses were performed to determine the independent impact of surveillance on oncologic outcomes and HRQL. Results: 4,682 patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy). 45.5% underwent IS. At a median follow-up of 60 months, 47.5% developed disease recurrence. Oligometastatic recurrence occurred in 39% of cases, with 31% receiving best supportive care, 60% chemotherapy and/or radiation, and 8% surgical resection. IS was associated with reduced symptomatic recurrence (odds ratio [OR] 0.17 [0.12–0.25]), increased tumor-directed therapy (OR 2.09 [1.58–2.77]), and improved OS (HR 0.90 [0.82–0.98], 5-year OS 47.9±1.2% versus 43.2±1.1%). After adjusting for confounders, significantly improved overall survival with IS was maintained for patients who underwent surgery alone as initial therapy (HR 0.60 [0.47–0.78]) and in those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58–0.89]). IS was associated with greater anxiety ( P= 0.016), but similar overall HRQL. Conclusions: These data suggest that IS may improve oncologic outcomes, particularly in patients with early stage disease at presentation or with a favorable pathological stage post induction therapy. This may be relevant to guideline development and provide a framework and rationale for RCTs. It may also inform shared decision-making with patients at a time where therapeutic options for recurrence are expanding.

Negative first follow-up prostate biopsy on active surveillance is associated with decreased risk of upgrading, suspicion of progression and converting to active treatment.

To determine the risk of disease progression and conversion to active treatment following a negative biopsy while on active surveillance (AS) for prostate cancer (PCa). Men on an AS programme at a single tertiary hospital (London, UK) between 2003 and 2018 with confirmed low-intermediate-risk PCa, Gleason Grade Group <3, clinical stage <T3 and a diagnostic prostate-specific antigen (PSA) level of <20ng/mL. This cohort included men diagnosed by transrectal ultrasonography guided (12-14 cores) or transperineal (median 32 cores) biopsy. Multivariate Cox hazards regression analysis was undertaken to determine (i) risk of upgrading, (ii) clinical or radiological suspicion of disease progression, and (iii) transitioning to active treatment. Suspicion of disease progression was defined as any biopsy upgrading, >30% positive cores, magnetic resonance imaging (MRI) Likert score >3/T3 or PSA level of >20ng/mL. Conversion to treatment included radical or hormonal treatment. Among the 460 eligible patients, 23% had negative follow-up biopsy findings. The median follow-up was 62months, with one to two repeat biopsies and two MRIs per patient during that period. Negative biopsy findings at first repeat biopsy were associated with decreased risk of converting to active treatment (hazard ration [HR] 0.18, 95% confidence interval [CI] 0.09-0.37; P<0.001), suspicion of disease progression (HR 0.56, 95% CI: 0.34-0.94; P=0.029), and upgrading (HR 0.48, 95% CI 0.23-0.99; P=0.047). Data are limited by fewer men with multiple follow-up biopsies. A negative biopsy finding at the first scheduled follow-up biopsy among men on AS for PCa was strongly associated with decreased risk of subsequent upgrading, clinical or radiological suspicion of disease progression, and conversion to active treatment. A less intense surveillance protocol should be considered for this cohort of patients.

UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants

Constitutional pathogenic variants in TP53 are associated with Li-Fraumeni syndrome or the more recently described heritable TP53-related cancer syndrome and are associated with increased lifetime risks of a wide spectrum...

Evidence-based follow-up in colorectal cancer—quo vadis?

SummaryColorectal cancer is the third most common and the third most lethal cancer disease in the western world. As most patients undergo treatment with curative intent at initial diagnosis, postoperative surveillance protocols have been established with the primary aim to detect possible disease recurrence in an early resectable stage. Various international guidelines recommend an intensive surveillance protocol over a 5-year time period. These guidelines are based on the reported significant benefit regarding overall patient survival, and on the observation that 90% of recurrences occur within the first 5 years following resection. Surveillance protocols include regular clinical examinations, measurement of the carcinoembryonic antigen, computed tomography scans and regular endoscopies. While there is plenty of evidence regarding the scheduling of endoscopies, the frequency of carcinoembryonic antigen measurements and computed tomography scans has been ever since under debate. The benefit of intensive compared to low frequency surveillance protocols regarding disease-specific survival has never been shown. Moreover, recent meta-analyses and randomized controlled trials challenge current guidelines. Intensive carcinoembryonic antigen assessment and computed tomography scan follow-up protocols seem to fail in generating better overall and disease-specific survival in colorectal cancer patients compared to less intensive surveillance strategies. This change over the last few decades parallels the treatment evolution of colorectal cancer from a primarily surgical to a multidisciplinary task. Instead of advocating a reduction of the follow-up intensity, these findings should stimulate the colorectal oncology field to move from a one-fits-all to a patient-centered surveillance.

Transforming human papillomavirus infection and the esophageal transformation zone: prime time for total excision/ablative therapy?

High-risk human papillomavirus (hr-HPV) infection is causal for almost all cervical malignancy (both squamous and adenocarcinoma), 90% of anal neoplasia, 70% of penile tumors, and 25% of head and neck cancers. The shared immunogenetics of cervical and esophageal malignancy suggests that HPV infection could well be a common denominator in the etiology of both cancers. In this regard, we have demonstrated that transcriptionally active hr-HPV (genotypes 16 and 18) is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma. Increasing hr-HPV viral load and integration status has been linked with greater disease severity along the Barrett metaplasia-dysplasia-adenocarcinoma sequence as has been demonstrated in cervical intraepithelial neoplasia and cancer. HPV infections in both the cervix and esophagus are both focal, i.e., present in greater quantities at the squamocolumnar junction (SCJ). HPV affinity is to junctional tissue, as basal cells are particularly accessible at the squamocolumnar transformation zone and especially susceptible to this viral infection. We have postulated that progressive acid damage to the esophagus increases the likelihood of mucosal breaks enabling the virus to enter the basal layer of the transformation zone. The SCJ is the transformation zone of the esophagus and is strikingly similar to the transition zone (ectoendocervical SCJ) of the uterine cervix where almost all high-grade cervical lesions and cancers arise including 80% of adenocarcinomas. These transition zone cells exhibit features of squamous epithelium as well as glandular cells, which have been described in both Barrett's esophagus and cervical mucosa. Barrett's esophagus (BE) is derived from a discrete population of embryonic cells residing at the SCJ. There is loss of SCJ immune-phenotype following excision without regeneration at other junctional sites. Prevention of cervical cancer in up to 80-95% of patients with screen-detected CIN is dependent on the excision/ablation of the entire transformation zone. The persistence of hr-HPV 16/18 following eradication of CIN is a significant risk factor for recurrence. Similarly, we have demonstrated that persistent hr-HPV infection 16/18 and p53 overexpression are associated with treatment failure after endoscopic ablation of BD/EAC. Thus, we believe that excision/ablation of the SCJ in patients with BD/intramucosal EAC should be performed to reduce the potential malignant risk. We propose to test this hypothesis by a multicenter randomized controlled trial whereby patients (both HPV positive and those which are virus negative) will be allocated into two arms: complete excision of the SCJ via endoscopic mucosal resection (EMR) in addition to radiofrequency ablation (RFA)± EMR of BD/intramucosal EAC (experimental arm) versus current standard of care (RFA ± EMR) of said lesions. Treatment efficacy in both groups will be evaluated by comparing disease elimination, regression/progression, and recurrence (if any). All patients would be entered into an intensive endoscopic surveillance protocol (biannually) for at least 2 years with lesional/neosquamous biopsies to compare the recurrence rate of both dysplasia/neoplasia in both arms. Viral (HPV DNA/p16INK4A/E6/E7 mRNA) and host biomarkers (e.g., p53) will be analyzed both at baseline and posttreatment intervals. A positive study would initiate development of tools best suited for SCJ destruction.

Active Surveillance Versus Watchful Waiting for Localized Prostate Cancer: A Model to Inform Decisions

BackgroundAn increasing proportion of prostate cancer is being managed conservatively. However, there are no randomized trials or consensus regarding the optimal follow-up strategy. ObjectiveTo compare life expectancy and quality of life between watchful waiting (WW) versus different strategies of active surveillance (AS). Design, setting, and participantsA Markov model was created for US men starting at age 50, diagnosed with localized prostate cancer who chose conservative management by WW or AS using different testing protocols (prostate-specific antigen every 3–6 mo, biopsy every 1–5 yr, or magnetic resonance imaging based). Transition probabilities and utilities were obtained from the literature. Outcome measurements and statistical analysisPrimary outcomes were life years and quality-adjusted life years (QALYs). Secondary outcomes include radical treatment, metastasis, and prostate cancer death. Results and limitationsAll AS strategies yielded more life years compared with WW. Lifetime risks of prostate cancer death and metastasis were, respectively, 5.42% and 6.40% with AS versus 8.72% and 10.30% with WW. AS yielded more QALYs than WW except in cohorts age >65 yr at diagnosis, or when treatment-related complications were long term. The preferred follow-up strategy was also sensitive to whether people value short-term over long-term benefits (time preference). Depending on the AS protocol, 30–41% underwent radical treatment within 10 yr. Extending the surveillance biopsy interval from 1 to 5 yr reduced life years slightly, with a 0.26 difference in QALYs. ConclusionsAS extends life more than WW, particularly for men with higher-risk features, but this is partly offset by the decrement in quality of life since many men eventually receive treatment. Patient summaryMore intensive active surveillance protocols extend life more than watchful waiting, but this is partly offset by decrements in quality of life from subsequent treatment.

Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort

Establishment of an optimal cancer surveillance program is important to reduce cancer-related morbidity and mortality in individuals with Li-Fraumeni syndrome, a rare, highly penetrant cancer predisposition syndrome. To determine the feasibility and efficacy of a comprehensive cancer screening regimen in Li-Fraumeni syndrome, using multiple radiologic techniques, including rapid whole-body magnetic resonance imaging (MRI) and laboratory measurements. Baseline evaluation of a prospective cancer screening study was conducted from June 1, 2012, to July 30, 2016, at the National Cancer Institute, National Institutes of Health (an academic research facility). Participants included 116 individuals with Li-Fraumeni syndrome with a germline TP53 pathogenic variant who were aged 3 years or older at the time of baseline screening and had not received active cancer therapy at least 6 months prior to screening. Detection of prevalent cancer with multimodal screening techniques and the need for additional evaluation. Of the 116 study participants, 77 (66.4%) were female; median age was 37.6 years (range, 3-68 years). Baseline cancer screening led to the diagnosis of cancer in 8 (6.9%) individuals (2 lung adenocarcinomas, 1 osteosarcoma, 1 sarcoma, 1 astrocytoma, 1 low-grade glioma, and 2 preinvasive breast cancers [ductal carcinoma in situ]); all but 1 required only resection for definitive treatment. A total of 40 (34.5%) participants required additional studies to further investigate abnormalities identified on screening, with 32 having incidental, benign, or normal findings, resulting in a false-positive rate of 29.6%. Non-MRI techniques, including baseline blood tests, abdominal ultrasonography in children, mammography, and colonoscopy, did not lead to a diagnosis of prevalent cancer in our cohort. This study describes the establishment and feasibility of an intensive cancer surveillance protocol for individuals with Li-Fraumeni syndrome. Prevalent cancers were detected at an early stage with baseline whole-body, brain, and breast MRI. Prospective screening of the participants is under way.

Nearly a Third of High-Grade Dysplasia and Colorectal Cancer Is Undetected in Patients with Inflammatory Bowel Disease.

It is unclear whether intensive surveillance protocols have resulted in a decreased incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD). To determine the prevalence and characteristics of IBD associated high-grade dysplasia (HGD) or CRC that was undetected on prior colonoscopy. This is a single-center, retrospective study from 1994 to 2013. All participants had a confirmed IBD diagnosis and underwent a colectomy with either HGD or CRC found in the colectomy specimen.The undetected group had no HGD or CRC on prior colonoscopies. The detected group had HGD or CRC identified on previous biopsies. Of 70 participants, with ulcerative colitis (UC) (n=47), Crohn's disease (CD) (n=21), and indeterminate colitis (n=2), 29% (n=20) had undetected HGD/CRC at colectomy (15 HGD and 5 CRC). In the undetected group, 75% had prior LGD, 15% had indefinite dysplasia, and 10% had no dysplasia (HGD was found in colonic strictures). Patients in the undetected group were more likely to have pancolitis (55 vs. 20%) and multifocal dysplasia (35 vs. 8%). The undetected group was less likely to have CRC at colectomy (25 vs. 62%). There was a trend toward right-sided HGD/CRC at colectomy (40 vs. 20%; p=0.08). In addition, 84% of the lesions found in the rectum at colectomy were not seen on prior colonoscopy in the undetected group. The prevalence of previously undetected HGD/CRC in IBD found at colectomy was 29%. The high proportion of undetected rectal and right-sided HGD/CRC suggests that these areas may need greater attention during surveillance.

Abstract 5016: Elevated serum monocyte chemotactic protein 4 (MCP4) as a novel noninvasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer

Abstract Purpose. Despite the recent progress in diagnosis and treatment for colorectal cancer (CRC), prognosis of CRC patients still remains poor. Metastatic recurrence is the major causes of cancer-related death in CRC patients, and recent progress in treatment options, especially technical advances in invasive treatment for metastatic lesion, have improved the prognosis of CRC patients with metastasis. Furthermore, almost half of patients that receive chemotherapy derive no clinical benefit, though all are exposed to these severe toxic and expensive therapeutic regimens in patients with metastatic CRC patients. In view of these underlying issues, for improvement of patient's prognosis, there is a keen interest in developing robust biomarkers that can identify the subset of patients who can benefit from intensive post-treatment surveillance protocols for early detection of recurrence, and prompt decision of appropriate treatment protocol. Herein, we systemically and comprehensively evaluated differentially levels of serum cytokines using array-based techniques to identify novel and reliable serum biomarker to predict metastasis and poor outcome in CRC. Methods. The study design included an initial dual screening phases, and followed by a subsequent clinical validation phase in this study.In discovery phase, we examined cytokine profiling using preoperative serum from two different CRC cohorts (n = 30) to identify differentially expressed serum cytokines in CRC patients with metastasis. In validation phase, serum levels of MCP-4 were assessed in 194 CRC patients by enzyme-linked immunosorbent assay, and their relationships with clinicopathological findings, including recurrence and survival, were investigated. Results. In discovery phase, three cytokines (elevated: MCP-4, ENA-78; decreased:Ckb8-1) were overlapped as a differentially expressed cytokines in serum from CRC patients with metastasis compared those without metastasis. High serum MCP-4 was significantly associated with older age (p = 0.033), advanced T stage (p = 0.029), distant metastasis (p = 0.011) and UICC stage classification (p = 0.006). Cox regression analysis showed that elevated MCP-4 was a significant and independent prognostic factor of disease free survival (HR:2.6, 95%CI:1.0-6.7) and overall survival (HR:2.7, 95%CI:1.3-5.9) in all CRC patients. Furthermore, logistic regression analysis revealed that high serum MCP-4 level was an independent marker in predicting distant metastasis in CRC (OR:3.8, 95%CI:1.3-10.9). Conclusion. Our comprehensive study highlights the clinical feasibility of serum MCP-4 as a prognostic and predictive biomarker for distant metastasis and recurrence in CRC patients. Quantification of serum MCP-4 concentration might support the early detection/prediction of recurrence and may contribute to the prediction of clinical outcomes in CRC. Citation Format: Yoshinaga Okugawa, Yuji Toiyama, Koji Tanaka, Mikio Kawamura, Takahito Kitajima, Tadanobu Shimura, Hiroki Imaoka, Hiroyuki Fujikawa, Susumu Saigusa, Yasuhiro Inoue, Motoyoshi Tanaka, Yasuhiko Mohri, Chikao Miki, Ajay Goel, Masato Kusunoki. Elevated serum monocyte chemotactic protein 4 (MCP4) as a novel noninvasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5016.

Management of non-muscle invasive bladder cancer: A comprehensive analysis of guidelines from the United States, Europe and Asia.

Bladder cancer is the 8th most common cancer with 74,000 new cases in the United States in 2015. Non-muscle invasive bladder cancer (NMIBC) accounts for 75% of all bladder cancer cases. Transurethral resection and intravesical treatments remain the main treatment modality. Up to 31-78% of cases recur, hence the need for intensive treatment and surveillance protocols which makes bladder cancer one of the most expensive cancers to manage. The purpose of this review is to compare contemporary guidelines from Europe, (European Association of Urology), the United States (National Comprehensive Cancer Network), the United Kingdom (National Institute for Health and Care Excellence), Japan (Japanese Urological Association) and the International Consultation on Bladder Cancer (ICUD). We compare and contrast the different guidelines and the evidence on which their recommendations are based.

MP15-07 SERIAL ANATOMIC PROSTATE ULTRASOUND IMAGING DURING PROSTATE CANCER ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II1 Apr 2016MP15-07 SERIAL ANATOMIC PROSTATE ULTRASOUND IMAGING DURING PROSTATE CANCER ACTIVE SURVEILLANCE Mohamed Eltemamy, Michael Leapman, Janet Cowan, Katsuto Shinohara, Antonio Westphalen, and Peter Carroll Mohamed EltemamyMohamed Eltemamy More articles by this author , Michael LeapmanMichael Leapman More articles by this author , Janet CowanJanet Cowan More articles by this author , Katsuto ShinoharaKatsuto Shinohara More articles by this author , Antonio WestphalenAntonio Westphalen More articles by this author , and Peter CarrollPeter Carroll More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2531AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The local growth potential of untreated low-grade prostate cancers (PCa) is unknown, yet potentially impactful for the practice of active surveillance (AS). We aimed to evaluate the incidence, growth dynamics and clinical significance of changes in prostate lesions on serial transrectal ultrasound (TRUS) imaging among a large cohort of men with PCa managed with AS. METHODS The retrospective study included men with PCa managed with AS at the University of California, San Francisco from 1990 to 2014 who received a minimum of two TRUS studies. Inclusion criteria were prostate-specific antigen (PSA) ≤ 20, clinical stage≤ T2 and biopsy Gleason grade ≤ 3+4. We described the presence of hypoechoic lesions at diagnosis. Progression endpoints included increase in imaging stage, ≥ 50% increase in volume, and increase in number of sites (sextants) with apparent lesions. The relationship between TRUS progression and biopsy Gleason upgrade was assessed using univariate and multivariate logistic regression models. RESULTS Among 713 identified patients the median number of TRUS studies was 5 (IQR 3-8), median follow up was 54 months (IQR 30-87). 407(57%) patients had TRUS-evident lesions at baseline. 281 (39%) patients progressed on serial TRUS imaging, including 55 by size, 209 by number of lesion sites and 211 by stage (median time to progression: 15 months). TRUS progression was independently associated with biopsy upgrade (OR 1.97, 95%CI 1.36-2.86, p < 0.01). Higher percentage of positive biopsy cores were associated with a higher likelihood of progression on TRUS (HR: 1.16; CI; 1.06-1.26; p<0.01) CONCLUSIONS Local progression, as assessed with TRUS, occurred in 39% of men AS and was associated with Gleason upgrade at biopsy. The median time to TRUS progression suggests that a less intense surveillance protocol is still safe. Percentage of biopsy positive cores should be used in tailoring AS protocols. The correlation of TRUS progression with biopsy upgrade might alter imaging and biopsy rates in those patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e154 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Mohamed Eltemamy More articles by this author Michael Leapman More articles by this author Janet Cowan More articles by this author Katsuto Shinohara More articles by this author Antonio Westphalen More articles by this author Peter Carroll More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation

Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n = 6) versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3] versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR, 20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month KL-6 levels continued to be higher in BOS group but were not statistically significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum of children receiving allo-SCT may identify patients at high risk for the development of BOS. These patients will benefit from intensive surveillance protocol and early therapy before irreversible lung damage.