Asymptomatic Metastatic Disease Research Articles

Abstract PD16-05: Systemic staging in breast cancer patients receiving neoadjuvant chemotherapy

Abstract Introduction Per NCCN guidelines, patients with stage I-III breast cancer should only have staging work up with CT chest, abdomen, and pelvis and bone scan if there are concerning symptoms, lab abnormalities, or physical exam findings. These patients do not require staging imaging because previous studies have documented the low incidence of metastatic disease found on systemic imaging, and the use of routine staging imaging has been shown to have a high false positive rate resulting in additional imaging and further work up with a low true positive rate. Despite the NCCN guidelines, extensive imaging is often performed prior to embarking on neoadjuvant therapy to look for evidence of metastatic spread of disease prior to surgery regardless of clinical stage and lack of symptoms. Methods We performed a retrospective analysis of patients at the University of Virginia diagnosed with invasive breast cancer who were recommended for neoadjuvant therapy and underwent systemic imaging to assess for the presence of distant metastatic breast cancer between 2012 and 2019. All receptor subtypes were included. Patients with signs/symptoms of metastatic disease at time of initial consultation were excluded. We evaluated the rate of metastatic breast cancer detected on systemic imaging. We also evaluated the rate of incidental findings on systemic imaging and how often this resulted in additional imaging or biopsy. Results 328 patients met inclusion criteria and were recommended for neoadjuvant chemotherapy and underwent systemic staging. Of these, 8 patients had bilateral breast cancer at time of diagnosis. Included patients were 54.2% hormone receptor (HR) positive, 35.4% triple negative, and 23.2% HER2 positive; 74.1% were node positive (Table 1). Metastatic breast cancer was identified in 9.1% (30 patients), which included 19 HR positive, 8 HER2 positive, and 7 triple negative patients. Of the patients found to have metastatic breast cancer, 80% had anatomic stage III disease at presentation and 93.3% were node positive. Two metastatic patients that were node negative had a cT2 or cT3 primary tumor. Systemic imaging identified incidental findings in 72.6% (238) patients. Most common incidental findings were pulmonary nodules (107), bone lesion or abnormality (71), hepatic lesions (55), and gynecologic lesions (50). Of the patients with incidental findings, 40.7% (98) underwent additional imaging for further work up or monitoring and 12.2% (29) underwent a biopsy or procedure for further work up. These biopsies identified benign or non-diagnostic results in 20 cases (69.0%) and identified an alternative malignancy in 9 cases (31%). Conclusions Within this study, asymptomatic metastatic disease was most commonly found in node positive stage III breast cancer, but was never or rarely found in stage I or II breast cancer patients. This validates NCCN recommendations that asymptomatic anatomic stage I or II breast cancer patients do not benefit from systemic staging. Yet, we did find a relatively high proportion of metastatic disease in asymptomatic patients with stage III breast cancer, indicating that systemic staging may be appropriate for this population. This must be balanced against the high probability of incidental findings with frequent additional imaging or biopsy, which has implications for patient anxiety, potential harm, and cost. Table 1: Patient Characteristics Citation Format: Courtney Lattimore, Squeo Gabriella, Christiana Brenin, Shayna Showalter, Trish Millard. Systemic staging in breast cancer patients receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD16-05.

Clinical Impact of Systemic Staging Studies in Secondary Breast Angiosarcoma

Our goal was to evaluate the clinical impact of local and systemic imaging in secondary breast angiosarcoma (SBAS) at diagnosis (DX) and in follow-up (FU). Singe-center retrospective review of SBAS treated from 1/2007-7/2020. Clinicopathologic data was collected, including local and systemic imaging at DX and FU. The clinical impact of imaging was evaluated. Twenty patients had SBAS diagnosed 10.6±6.7 years following their index BC. All were diagnosed on exam. Mammogram, ultrasound, and breast MRI were commonly performed concurrently with DX (2.4 studies per patient) but did not impact clinical management. In-breast imaging extent of disease did not correlate with pathologic extent of disease (p=0.49). Systemic staging uncommonly identified asymptomatic metastatic disease (5%). During FU, 90% of recurrences were identified by exam or new symptoms, not routine imaging. SBAS extent is not reliably estimated on targeted breast imaging. Asymptomatic metastatic disease is uncommon but targeted evaluation of new symptoms is warranted given high likelihood of identifying metastasis. Additional data is needed to define optimum imaging timing and modalities for SBAS.

Abstract PD13-09: Impact of neratinib on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial

Abstract Background: The development of central nervous system (CNS) metastases presents a considerable challenge in metastatic breast cancer (MBC) due to the limited availability of evidence-based treatments. Up to 50% of patients with HER2-positive (HER2+) MBC develop CNS metastases during the course of their disease. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated activity against CNS metastases in HER2+ MBC in two phase 2 studies (NEfERT-T, TBCRC 022) and one phase 3 study (NALA); significant benefits for predefined CNS endpoints were reported in NEfERT-T and confirmed in NALA. Here we present an exploratory analysis of patients from NALA with CNS involvement at enrollment. Methods: NALA was an international, randomized, open-label, active-controlled, phase 3 study in patients with HER2+ MBC who had received ≥2 lines of HER2-directed therapy in the metastatic setting (ClinicalTrials.gov: NCT01808573). Patients with asymptomatic metastatic brain disease managed with stable doses of corticosteroids for ≥14 days prior to randomization were eligible, whereas patients with symptomatic or unstable brain metastases were excluded. Patients were randomized (1:1 ratio) to neratinib (N; 240 mg qd po) + capecitabine (C; 750 mg/m2 bid po) or lapatinib (L; 1250 mg qd po) + C (1000 mg/m2 bid po). Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Intervention for symptomatic metastatic CNS disease was a secondary endpoint. CNS disease at baseline was defined as patients with treated or untreated disease in the ‘brain’ assessed by investigator at enrollment. CNS imaging was not mandatory at screening. Results: Of the 621 patients enrolled in NALA, 101 (16%) had documented baseline CNS disease and 520 (74%) had no CNS disease at baseline. Patients with CNS disease had a lower performance status and were more likely to have hormone receptor-negative disease than those with no CNS disease; no major imbalances of baseline characteristics were noted between treatment arms. Overall, 78 (77%) patients had previously received CNS radiation [whole brain, n=59 (58%); stereotactic, n=17 (17%); unknown, n=2 (2%)], and 5 (5%) patients had undergone CNS surgery. Median treatment duration was 5.7 (IQR 2.8-8.5) months for N, and 3.5 (IQR 2.1-6.9) months for L. PFS, OS, and cumulative incidence of interventions for symptomatic CNS disease are summarized in the table. No new safety signals were detected. Conclusions: Regardless of the status of CNS metastases at baseline, patients appeared to have better outcomes in the N+C arm compared with the L+C arm. Table. Efficacy outcomes in patients with and without CNS disease at baselineIntention-to-treat (n=621)CNS metastases at baseline – Yes (n=101)CNS metastases at baseline – No (n=520)N+C (n=307)L+C (n=314)N+C (n=51)L+C (n=50)N+C (n=256)L+C (n=264)PFSaHazard ratio (95% CI)0.76 (0.63–0.93)0.66 (0.41–1.05)0.76 (0.62–0.94)P-value0.00590.07410.0099Restricted mean PFSb, months8.86.67.85.59.06.9Difference, months2.22.32.1OSHazard ratio (95% CI)0.88 (0.72–1.07)0.90 (0.59–1.38)0.85 (0.68–1.06)P-value0.20860.63520.1517Restricted mean OSb, months24.022.216.415.425.623.6Difference, months1.71.02.0Incidence of CNS interventionOverall cumulative incidencec, %22.7629.1940.1347.7919.1624.65P-value0.0430.4300.067aCentrally confirmed; bRestriction prespecified as 24 months for PFS, and 48 months for OS; c % requiring intervention for CNS disease (competing risk model) Citation Format: Cristina Saura, Larisa Ryvo, Sara Hurvitz, William Gradishar, Beverly Moy, Suzette Delaloge, Sung-Bae Kim, Mafalda Oliveira, Maureen Trudeau, Ming-Shen Dai, Barbara Haley, Ron Bose, Luciana Landeiro, Judith Bebchuk, Aimee Frazier, Kiana Keyvanjah, Richard Bryce, Adam Brufsky. Impact of neratinib on outcomes in HER2-positive metastatic breast cancer patients with central nervous system disease at baseline: Findings from the phase 3 NALA trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-09.

An Unusual Case of Metastatic Breast Cancer in the Colon

Brest cancer metastasis to the gastrointestinal tract is rare. The majority of reported cases include exams prompted by symptoms and are usually of lobular origin with gastric metastases being more common than colonic. We present a rare case of metastatic invasive ductal carcinoma of the breast diagnosed by polypectomy of a benign appearing colon polyp during a screening colonoscopy. A 70 year old female with past medical history significant for bilateral, triple negative, infiltrating ductal carcinoma status post resection, radiation and chemotherapy was referred for endoscopic ultrasound after surveillance imaging showed enlarging lymph nodes. There were no reported gastrointestinal symptoms on thorough history and exam and blood work showed no abnormality. She was scheduled to undergo both EGD with EUS and a colonoscopy as she was due for screening. EGD with EUS confirmed CT findings of lymphadenopathy; the largest node measured 22 x 11 mm in diameter was biopsied. Colonoscopy revealed one flat 4 mm polyp in the descending colon, which was resected. Surprisingly, pathology of the benign appearing colon polyp and the lymph node showed metastatic adenocarcinoma consistent with mammary primary. Unfortunately due to tumor biology she was not a candidate for available clinical trials and was initiated on palliative chemotherapy with gemcitabine, however her cancer was rapidly progressive and she entered hospice three months after EGD. This case highlights a rare location for metastasis that may have been missed without screening colonoscopy. Our patient's findings are unique in that the majority of metastatic breast cancer lesions to the colon are often identified on surveillance scans and/or symptoms that prompt diagnostic colonoscopies. Our patient's triple negativity most likely contributed to its rapid progression, which further confounds its benign appearance on colonoscopy. Though rare, cases like ours represent an opportunity to emphasize the importance of screening even if a patient's disease is stable. This case calls into question whether screening guidelines should be altered in patients with malignancy in order to identify GI metastases prior to symptom development. While in our patient, the early discovery of asymptomatic metastatic disease did not have a significant effect on progression, one must wonder if more aggressive surveillance with endoscopy could be helpful in patients with a more favorable cytogenetic profile.

Meta-analysis of colorectal cancer follow-up after potentially curative resection

BackgroundAfter potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier.MethodsA systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer.ResultsThere were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5–24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11).ConclusionBased on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

MP73-12 UNSUSPECTED METASTASES FOUND DURING SCREENING FOR A TRIAL OF PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2015MP73-12 UNSUSPECTED METASTASES FOUND DURING SCREENING FOR A TRIAL OF PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER E. David Crawford, Jannell R. DePalantino, Philip W. Kantoff, Neal Shore, Willie Underwood, Vijay Reddy, Jim Wang, Suneel Mundle, Zane Yang, Tracy McGowan, and Charles J. Ryan E. David CrawfordE. David Crawford More articles by this author , Jannell R. DePalantinoJannell R. DePalantino More articles by this author , Philip W. KantoffPhilip W. Kantoff More articles by this author , Neal ShoreNeal Shore More articles by this author , Willie UnderwoodWillie Underwood More articles by this author , Vijay ReddyVijay Reddy More articles by this author , Jim WangJim Wang More articles by this author , Suneel MundleSuneel Mundle More articles by this author , Zane YangZane Yang More articles by this author , Tracy McGowanTracy McGowan More articles by this author , and Charles J. RyanCharles J. Ryan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2688AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Factors associated with rates of progression from non-metastatic to metastatic castration resistant prostate cancer (CRPC) have been described.1,2 We used this information to identify patients at high risk for progression from non-metastatic to metastatic disease (MD) for entry into the IMpact of Abiraterone Acetate in Prostate Specific AntiGEN (IMAAGEN) trial. To report the high rate of unsuspected metastases in asymptomatic patients with CRPC, leading to screen failure. METHODS From April 2011-July 2013, patients were screened for entry into the IMAAGEN trial. Key entry criteria included having CRPC as defined by a rising PSA and a serum T < 50 ng/dL and a PSA ≥ 10 ng/mL or PSA doubling time (PSADT) ≤ 10 months. Primary endpoint of IMAAGEN was proportion of subjects achieving a ≥ 50% reduction in PSA by 6 cycles of treatment. During screening, patients who met entry criteria based on laboratory results underwent imaging studies to screen for local disease progression or MD. RESULTS 298 patients were screened. 167 (56%) patients screen failed. 77 patients had MD, which represents 37% of 208 patients who, by lab results, were eligible for and underwent imaging studies. We will report on the relationship of unsuspected MD to PSA/PSADT entry criteria. CONCLUSIONS A high rate of unsuspected asymptomatic MD was found in this high-risk CRPC patient population (PSA ≥ 10 ng/mL or PSADT ≤ 10months). Our findings build upon other reported data on MD discovered during screening for non-metastatic CRPC trials.3 These findings suggest the need to prospectively define risk factors for development of MD in CRPC to assure timely identification, especially in light of new treatment options. 1Smith MR, Kabbinavar F, Saad F et al. Natural History of Rising Serum Prostate-Specific Antigen in Men with Castrate Nonmetastatic Prostate Cancer. J Clin Oncol 2005;23:2918-2925. 2Smith MR, Cook R, Lee K et al. Disease and Host Characteristics as Predictors of Time to First Bone Metastasis and Death in Men with Progressive Castration-Resistant Nonmetastatic Prostate Cancer. Cancer 2011;117:2077-85. 3Yu EY, Miller K, Nelson J et al. Detection of previously unidentified metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer. J Urol 2012;188:103-109. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e934 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information E. David Crawford More articles by this author Jannell R. DePalantino More articles by this author Philip W. Kantoff More articles by this author Neal Shore More articles by this author Willie Underwood More articles by this author Vijay Reddy More articles by this author Jim Wang More articles by this author Suneel Mundle More articles by this author Zane Yang More articles by this author Tracy McGowan More articles by this author Charles J. Ryan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD38-02 METASTATIC PROSTATE CANCER IN THE MODERN ERA OF PSA SCREENING

You have accessJournal of UrologyProstate Cancer: Detection and Screening III1 Apr 2015PD38-02 METASTATIC PROSTATE CANCER IN THE MODERN ERA OF PSA SCREENING Philip Fontenot, Avinash Nehra, Hadley Wyre, Moben Mirza, Jeffrey Holzbeierlein, J. Brantley Thrasher, Peter Van Veldhuizen, and Eugene Lee Philip FontenotPhilip Fontenot More articles by this author , Avinash NehraAvinash Nehra More articles by this author , Hadley WyreHadley Wyre More articles by this author , Moben MirzaMoben Mirza More articles by this author , Jeffrey HolzbeierleinJeffrey Holzbeierlein More articles by this author , J. Brantley ThrasherJ. Brantley Thrasher More articles by this author , Peter Van VeldhuizenPeter Van Veldhuizen More articles by this author , and Eugene LeeEugene Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2423AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer continues to be the second leading cause of cancer death in American men. Studies evaluating the benefit of screening have been controversial and there has been no universal consensus. Our objective was to characterize the initial presentation and PSA screening in men who have metastasis and/or have died of disease in a contemporary cohort. METHODS After IRB approval, the medical records of 93 men diagnosed with metastatic prostate cancer or who died of disease between 2008 to 2014 were evaluated. First, we assessed the method of initial presentation and placed them into four groups. Groups 1 and 2 presented initially with presumed localized disease and were treated with surgery or radiation but recurred late (>1 year; Group 1) or early (<1 year; Group 2). Groups 3 and 4 were patients who presented with asymptomatic (Group 3) and symptomatic (Group 4) metastatic disease. For each group, we evaluated the trend of PSA screening. Patients who had their first PSA test prior to the age of 55 were considered to have undergone standard screening. RESULTS In our cohort, groups 1, 2, 3 and 4 had 22 (24%), 4 (4%), 35 (38%) and 32 (34%) patients, respectively. In Group 1, while 20/22 (91%) patients had a PSA prior to primary treatment, only 4 (18%) had undergone standard PSA screening with a first test before the age of 55. In Group 2, we had PSA data on 3 patients of which 0/3 (0%) received standard screening. In Group 3, 9/33 (28%) underwent standard screening prior to presentation with asymptomatic metastatic disease. In Group 4, 3/32 (9%) patients had undergone standard screening prior to presentation with symptomatic metastatic disease. CONCLUSIONS Despite widespread screening efforts during the timeframe of this analysis, the majority of patients with clinically relevant prostate cancer (metastasis and/or death from prostate cancer) presented with metastatic disease 67/93 (72%). Furthermore, in the entire cohort, only 19/90 (21%) patients had received standard PSA screening before the age of 55. This data underscores the notion that despite mass screening, patients who develop incurable disease are not failures of screening but never undergo appropriate testing in the first place. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e824-e825 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Philip Fontenot More articles by this author Avinash Nehra More articles by this author Hadley Wyre More articles by this author Moben Mirza More articles by this author Jeffrey Holzbeierlein More articles by this author J. Brantley Thrasher More articles by this author Peter Van Veldhuizen More articles by this author Eugene Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Osteopoikilosis: A Benign Condition With the Appearance of Metastatic Bone Disease

Case Report A 37-year-old woman with a history of migraines and gastritis presented to the emergency department with 1 day of right adnexal pain. A computed tomography (CT) scan of the pelvis performed to evaluate the pelvic pain showed a fluid-filled structure in the right adnexa, indicating a possible tubo-ovarian abscess. The patient was subsequently admitted to the hospital for treatment with antibiotics. Incidentally found on CT imaging were diffuse sclerotic foci (Fig 1) throughout the visualized spine and pelvis, suggesting asymptomatic metastatic disease. Physical examination was only significant for right lower quadrant tenderness, corresponding to the CT findings. There was no lymphadenopathy, mass, or obvious tenderness of her spine and pelvis. Initial laboratory results showedanormalcompletebloodcountandserumchemistries, including calcium of 9.8 mg/dL, and alkaline phosphatase of 63 U/L, and normal CA125 level. CT imaging of the chest showed diffuse blastic-appearing lesions throughout the skeleton without notable lymphadenopathy or mass. A nuclear bone scan was found to be normal, without evidence of any blastic metastatic lesions (Fig 2). The patient was ultimately given the diagnosis of osteopoikilosis, a rare benign condition of the bone.

CT or not CT? How should we look for distant metastases in invasive breast cancer in NHS highland?

Introduction Invasive breast cancer can metastasize to distant organs. SIGN (1) Guidelines (84) suggest that no staging is required for T1-2 N0-1 tumours in asymptomatic women . Aims To identify an effective strategy for staging investigations in NHS Highland. M et hod s (including ethical approval) Data from all patients with invasive breast cancer diagnosed over a 6 month period were retrieved from a prospectively maintained database. Investigations used as a staging strategy were recorded. Ethical approval not required Results 111 patients were diagnosed with invasive breast cancer. 98 patients went on to have surgery. 5 patients with asymptomatic metastatic disease were identified in the pre/peri-operative period. 3 of patients did not have surgery due to advanced disease. Conclusions CT chest/abdomen/pelvis is now used as the primary staging investigation for asymptomatic metastases in patients with: Preoperative clinically bulky nodes 4 nodes positive on post-operative histology Patients considered for reconstruction References (1) SIGN 84 Management of Breast Cancer in Women: A National Clinical Guideline December 2005

Quality of post-treatment surveillance of early stage breast cancer in Texas

Only annual mammography and physical examination are recommended for the post-treatment surveillance of early stage breast cancer. We used Texas Cancer Registry-Medicare linked data (2001-2007) to identify physician visits and use of mammography, magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) CT in patients ≥ 66 years old with ductal carcinoma in situ and stage I-III ductal carcinoma who underwent curative-intent operations. We also evaluated the trends in use of recommended and nonrecommended tests. We identified 8,598 patients with resected ductal carcinoma in situ (37.3%) or invasive ductal cancer (62.7%). Breast-conserving therapy was performed in 59%. Only 55% saw a physician twice a year for 2 years and underwent annual mammography for 2 consecutive years in the surveillance period. Mammography use decreased from 81% in 2001 to 75% in 2007 (P < .0001), and breast MRI use rose from 0.5% to 7.0% (P < .0001). For asymptomatic patients, the use of CT/MRI of the abdomen, chest, and head was 27%, 23%, and 22%, and this slightly increased during the study period. There was a significant increase in PET/PET CT use, from 2% in 2001 to 9% in 2007 (P < .0001). There was a concomitant decrease in bone scan use from 21% in 2001 to 13% in 2007 (P < .0001). Adherence to evidence-based guidelines has been substandard and the use of nonrecommended tests has persisted over the study period. The rise in PET use and attendant decrease in bone scan implicates a population receiving PET scan in lieu of bone scan for surveillance of asymptomatic metastatic disease. In an elderly population of breast cancer patients in Texas, these findings imply both underuse and overuse.

Detection of metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

4655 Background: Many patients with biochemical relapse after definitive therapy for prostate cancer receive androgen deprivation therapy. PSA levels eventually will rise despite castrate levels of testosterone. Many of these patients have nonmetastatic disease and do not develop metastases for a median of 30 mos (Smith MR JCO, 2005). However, there is no standard therapy for patients with nonmetastatic CRPC. ENTHUSE M0 (Study 15) is a global phase III study, now closed to enrollment, comparing zibotentan 10 mg vs placebo in nonmetastatic CRPC patients. Coprimary endpoints are overall survival and radiographic progression or death. Patients are screened for metastases by bone and CT/MRI scans. An unexpectedly high number of patients failed screening, prompting this analysis. Methods: All screened patients were included. For each investigator, the number of patients who enrolled and who failed screening were recorded. Screen fail reasons were recorded. Screen failure rates were computed by clinical specialty (oncology or urology) and geographic region by dividing the number of screen failures by the number of enrolled patients in each category. Results: As of January 14, 2011, 2583 patients completed screening, and 1169 (45%) failed screening. Screen failure rates were not different by clinical specialty or by geographic region. The leading causes of screen failures by clinical specialty are listed in the table. Conclusions: These data suggest that detectable asymptomatic metastatic disease may exist in about 30% of presumed nonmetastatic CRPC. These findings stress the value of periodic staging studies in men with CRPC, as those with detectable metastatic CRPC may benefit from emerging therapies. Screen failure criteria, n (%) Oncology (631 patients enrolled) Urology (1,885 patients enrolled) Detection of metastatic disease 184 (29) 566 (30) Creatinine clearance of <50 mL/min 45 (7) 156 (8) Long QTc interval 24 (4) 82 (4) Absence of biochemical progression 27 (4) 76 (4) Testosterone level >70 ng/dL (noncastrate) 15 (2) 71 (4) Total screen failures, n 283* 873* * Some patients had >1 reason for screening failure.

Thyroid cancer: burden of illness and management of disease.

The incidence of thyroid cancer, the most common endocrine malignancy, has increased dramatically in the last fifty years. This article will review the standard approach to thyroid cancer treatment as well as novel therapies under investigation. We will also address potential cost considerations in the management of thyroid cancer. A comprehensive literature search was performed. Review article. The high prevalence of thyroid cancer and the availability of novel therapies for patients with metastatic disease have potential economic implications that have not been well-studied. Because many patients likely have very low morbidity from their cancers, better tools to identify the lowest risk patients are needed in order to prevent overtreatment. Improved risk stratification should include recognizing patients who are unlikely to benefit from radioactive iodine therapy after initial surgery and identifying those with indolent and asymptomatic metastatic disease that are unlikely to benefit from novel therapies. In patients with advanced incurable disease, randomized-controlled studies to assess the efficacy of novel agents are needed to determine if the costs associated with new agents are warranted. Health care costs associated with the increased diagnosis of thyroid cancer remain unknown but are worthy of further research.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case against.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case against.

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for

Extended follow-up of breast cancer patients in clinic wastes time for both patients and doctors: the case for

Chemotherapy for Hormone-Refractory Prostate Cancer: Now It's a Question of “When?”

Recently, data from two randomized phase III studies that compared docetaxel-based chemotherapy to mitoxantrone-based therapy demonstrated that treatment with docetaxel can prolong life in a significant way for patients with hormone-refractory prostate cancer. For many patients who experience disease progression after androgen-deprivation therapy, however, chemotherapy may not be immediately indicated. Such cases include those individuals with hormone-refractory disease in the absence of clinical metastases, and those with asymptomatic metastatic disease, for example. As a result, clinicians treating patients with hormone-refractory disease must weigh the benefits of earlier chemotherapy against its risks, and may consider other therapies such as secondary hormonal approaches before initiating chemotherapy. This decision is further complicated by the fact that a phase III study designed to compare secondary hormonal therapy with chemotherapy has failed due to lack of accrual. Furthermore, the limitations of chemotherapy for prostate cancer are being clarified and include a lack of standard second-line therapy as well as uncertain benefits for those with nonmetastatic disease. In this review, we will highlight some of the issues that impact on the decision of when to start chemotherapy and in whom as well as the potential benefits of secondary hormonal approaches.

Variates of Survival in Metastatic Uveal Melanoma

The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.

Differentiation and Definition of Vascular-Targeted Therapies

The therapeutic potential of targeting the tumor vascular supply is now widely recognized. Intense research and development activity has resulted in a variety of investigational agents, a number of which are currently in clinical development. As these novel agents are quite distinct from the cytotoxic drugs conventionally used in the treatment of solid tumors, it will be particularly important to ensure early differentiation of these vascular-targeted therapies in order to encourage widespread understanding of their potential benefits and application in the clinic. Two distinct groups of vascular-targeted therapies have evolved: antiangiogenic agents and vascular-disrupting approaches. These differ in three key respects: their physiologic target, the type or extent of disease that is likely to be susceptible, and the treatment scheduling. Inhibitors of angiogenesis interfere with new vessel formation and therefore have a preventative action, require chronic administration, and are likely to be of particular benefit in early-stage or asymptomatic metastatic disease. Vascular-disrupting agents target the established tumor blood vessels, resulting in tumor ischemia and necrosis. These agents are therefore given acutely, show more immediate effects, and may have particular efficacy against advanced disease. It is essential that these agents can be readily distinguished from conventional therapies and that an understanding of key differences between the two types of vascular-targeted therapies is fostered. Here, a simple taxonomy and nomenclature is proposed in anticipation that the therapeutic potential of this novel class can be realized as these approaches advance in clinical settings and a new anticancer strategy becomes available in the clinic.

L?hormonoth�rapie de la phase m�tastatique, n�o-adjuvante et adjuvante

For more than 60 years, the treatment of metastatic prostate cancer has been based on andro- gen deprivation. In the case of asymptomatic metastatic disease, the timing of hormonal therapy remains controversial. No evidence of a beneficial effect of neoadjuvant hormonal therapy before radical prostatectomy has been docu- mented. Radical prostatectomy and adjuvant therapy cannot be consi- dered as a standard treatment. There is a general consensus at this time that patients with high-grade localized tumors benefit from hormone therapy (2-3 years) in conjunction with external beam radiation therapy.

Early versus late hormonal therapy for prostate cancer.

Hormonal therapy remains the critical therapeutic option for men with advanced prostate cancer. However, considerable uncertainty remains regarding the appropriate choice/timing and actual benefits of hormonal therapy in various situations. This article reviews the relevant studies of immediate versus deferred hormonal therapy in patients with prostate cancer. The evidence from the data supports that early treatment is beneficial to many patients. Significant survival benefit of early hormonal therapy has been observed among patients with asymptomatic metastatic disease, node-positive but clinically localized disease after radical prostatectomy and lymphadenectomy, and advanced local/regional disease during and after radiotherapy.

British urological surgery practice: 1. Prostate cancer.

To investigate the treatment of prostate cancer in the United Kingdom. A postal survey was conducted of consultant urologists and general surgeons with an interest in urology to assess the current patterns of management of patients with prostate cancer in the UK and to determine patterns of clinical practice. Two-hundred and seventy-four replies were analysed. Radical radiotherapy (50%) and radical prostatectomy (29%) were the most favoured treatment options for patients < 70 years old with poorly differentiated T1 disease; for those aged > 70 years, active treatment was favoured by 183 (67%) consultants with radical radiotherapy (37%) and hormonal intervention (29%) the most frequent choices. In well-differentiated T1 disease, active treatment was favoured by 226 (83%) of consultants for patients < 70 years, with radical prostatectomy (44%) the most frequent choice. For patients > 70 years, observational management was preferred by 190 (69%) of consultants. In poorly differentiated T1 prostate cancer, active treatment was favoured by 252 (91%) for patients < 70, with radiotherapy (50%) the most frequent choice and for patients > 70 years, active treatment was favoured by 67% with radical radiotherapy the most common preference being chosen, by 102 (37%). For asymptomatic locally advanced disease, 55% of consultants favoured active treatment, whilst 63% favoured the active treatment of asymptomatic metastatic disease. For patients with symptomatic metastatic disease, GnRH agonist therapy was the treatment of choice of 66% of urologists and was given as monotherapy by 44% or as part of maximal androgen blockade by 22%. In clinical practice, 82% of urologists have close links with oncology, available through joint clinics or on-site referral. However, < 5% of urologists refer patients to an oncologist before the development of hormone refractory disease. At relapse, only 53% of urologists referred their patients to oncologists or palliative-care clinicians. A wide variety of hormonal treatments was offered at relapse; only 24% of urologists treated their patients by antiandrogen withdrawal or introduction, which is currently the most effective second-line hormonal treatment for recurrent prostate cancer. There is a wide variation in the clinical management of prostate cancer and we recommend the establishment of standards of practice.