Unfavorable Tumor Characteristics Research Articles

The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-G]) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and nonclassical MHC class I using the following monoclonal antibodies: 4H84 (anti-HLA-G), beta2-m (anti-beta-2-microglobulin) and HC-10 (MHC class I antigen heavy chain). Expression data were linked to known clinicopathological characteristics and survival. HLA-G upregulation and MHC class I downregulation in neoplastic cells was observed in 40% and 48%, respectively. Nonendometrioid tumor type, advanced stage disease (FIGO stage > or = II) and poorly or undifferentiated tumors were associated with MHC class I downregulation. Absence of HLA-G expression was independently associated with MHC class I downregulation. In univariate analysis, MHC class I downregulation was a predictor of worse disease-specific survival. Prognostic unfavorable tumor characteristics were correlated with downregulation of MHC class I expression in endometrial cancer cells. Furthermore, downregulated MHC class I has a negative impact on disease-specific survival, observed in a large cohort of patients with endometrial cancer. As there seems to be a relation between classical and nonclassical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism.

Body Mass Index and Prostate Specific Antigen as Predictors of Adverse Pathology and Biochemical Recurrence After Prostatectomy

Preoperative prostate specific antigen is widely used to predict unfavorable pathological features and biochemical relapse after radical prostatectomy. Recent reports that hemodilution may be responsible for lower prostate specific antigen in obese men led to concerns that prostate specific antigen may be less effective for prognosticating in men with increased body mass index. We determined whether the clinical usefulness of prostate specific antigen is negatively impacted by obesity by examining its operating characteristics and predictive accuracy as a function of body mass index. We performed a multicenter retrospective analysis of the records of 11,705 men who underwent radical prostatectomy from 1988 to 2007 from Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital Database, the Duke Prostate Center and Johns Hopkins Hospital. ROC curve analysis, the concordance index and the test for interaction were used to compare the ability of prostate specific antigen to predict unfavorable tumor characteristics and biochemical recurrence across body mass index categories. There were no significant differences in the area under ROC curves across increasing body mass index categories for prostate specific antigen to predict pathological Gleason sum (7 or greater, 7 [4 + 3] or greater, or 8 or greater), positive surgical margins, extracapsular extension or seminal vesicle invasion in all 3 cohorts. There was no significant difference in prostate specific antigen accuracy to predict biochemical failure across increasing body mass index categories. In 3 cohorts of men treated with radical prostatectomy the ability of preoperative prostate specific antigen to predict adverse pathological features and posttreatment biochemical recurrence is not significantly affected by obesity. However, adjusting for obesity related hemodilution may still be required to properly interpret prostate specific antigen results in men with increased body mass index.

Matched-pair analysis of female and male breast cancer: a comprehensive cohort study.

Abstract Abstract #4129 Introduction:
 Male breast cancer (MBC) is a rare disease accounting for approximately 1% of all breast carcinomas. Due to the low incidence treatment guidelines based on prospective studies are lacking. Presently treatment recommendations are derived from the standards for female breast cancer. However, those approaches might be inadequate because of distinct gender specific differences in tumor biology of breast cancer. This study was planned in order to elucidate potential differences between female and male breast cancer in both tumor biological behavior and clinical practice.
 Patients and Methods:
 MBC diagnosed 1995-2007 (region Chemnitz/Zwickau, Saxony, Germany) was retrospectively analyzed. Tumor characteristics, treatment and follow-up of the patients were documented. In order to highlight potential differences matched-pairs of female and male breast cancer patients were created. Each MBC was matched with a female counterpart (FBC) that showed accordance in at least 5-7 tumor characteristics (age, TNM, grade, hormone receptors, HER2 stage).
 Results:
 FBC and MBC (n=113 patients each) were evaluable for this analysis. For MBC the following tumor characteristics were documented: >60% advanced stages (T2-4), only 6% well differentiated, 42.5% nodal-positive, 86% hormone-sensitive (ER-positive 79.2%, PR-positive 76.9%), 6.2% HER2 positive.
 83.2% of MBC had a mastectomy/axillary dissection (FBC 49.0%), 55% adjuvant radiotherapy (FBC 66.7%), 64% adjuvant systemic therapy (FBC 80.6%), 32.7% chemotherapy (FBC 49.5%) and 47.8% endocrine treatment (FBC 60.1%). 31% of MBC had a relapse (FBC 25.9%), 68.1% overall survival (OS) (FBC 70.4%), 98 months (FBC 76 months) median survival time. In univariate analyses reduced OS of MBC was significant associated with advanced tumor stages (p<.005), poor histological grade (p<.05), receptor negative (p<.05) and nodal-positive tumors (p<.05). Furthermore adjuvant radiotherapy showed survival benefit. However, in multivariate analysis only tumor stage showed statistical significance (p<.01). Regarding these tumor characteristics no OS differences could be observed between FBC and MBC. However, MBC showed a trend to a shortened survival for receptor negative tumors in comparison to FBC (p=.055).
 Discussion:
 1. Delayed diagnosis of MBC; 2. Our study showed more advanced and undifferentiated tumors with a high percentage of nodal positivity; 3. In our analysis these unfavorable tumor characteristics were not related to a poor OS; 4. We found no significant differences regarding disease outcome between FBC and MBC; despite of a more aggressive adjuvant treatment for FBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4129.

Distinct Subcellular Expression Patterns of Neutral Endopeptidase (CD10) in Prostate Cancer Predict Diverging Clinical Courses in Surgically Treated Patients

Neutral endopeptidase (CD10), an ectopeptidase bound to the cell surface, is thought to be a potential prognostic marker for prostate cancer. Prostate cancer patients (N = 3,261) treated by radical prostatectomy at a single institution were evaluated by using tissue microarray. Follow-up data were available for 2,385 patients. The cellular domain (membranous, membranous-cytoplasmatic, and cytoplasmatic only) of CD10 expression was analyzed immunohistochemically and correlated with various clinical and histopathologic features of the tumors. CD10 expression was detected in 62.2% of cancer samples and occurred preferentially in higher Gleason pattern (P < 0.0001). CD10 expression positively correlated with adverse tumor features such as elevated preoperative prostate-specific antigen (PSA), higher Gleason score, and advanced stage (P < 0.0001 each). Survival analyses showed that PSA recurrence was significantly associated with the staining pattern of CD10 expression. Outcome significantly declined from negative over membranous, membranous-cytoplasmatic, to exclusively cytoplasmatic CD10 expression (P < 0.0001). In multivariate analysis, CD10 expression was an independent predictor for PSA failure (P = 0.0343). CD10 expression is an unfavorable independent risk factor in prostate cancer. The subcellular location of CD10 protein is associated with specific clinical courses, suggesting an effect on different important biological properties of prostate cancer cells. The frequent expression of CD10 in prostate cancer and the strong association of CD10 with unfavorable tumor features may qualify this biomarker for targeted therapies.

PCN94 COST-EFFECTIVENESS AND PREFERENCE FOR FOLLOW-UP SCENARIOS FOLLOWING BREAST CANCER

OBJECTIVES: About one in every eight women in The Netherlands develops breast cancer. Every year, 11,000 new cases are registered and about 3500 women die of breast cancer. Prognosis after primary treatment for patients with breast cancer is improving. This leads to an increased number of patients in follow-up, which leads to increased workload. One of the main goals of follow-up is to improve the survival of patients. This study aims to determine a more individualized follow-up by modelling costeffectiveness of various follow-up scenarios and by determining individual preferences by using a discrete choice experiment (DCE). METHODS: A discrete-event state-transition model was developed to estimate the cost-effectiveness of all scenarios for all patient groups. In addition, a discrete choice experiment (DCE) was designed to establish patient preferences. The DCE incorporated three process attributes (duration of follow-up, frequency and type of consult) and data were collected in a sample of 125 breast cancer patients. Patients had to complete all 18 choice sets that were generated from the three attributes. RESULTS: The modelling study revealed recommendations for follow-up in different age categories. Patients younger than 40 and patients with unfavorable tumor characteristics (>3 lymph nodes, tumor size >2 cm) can benefit from a more intensive follow-up of five or possibly ten years. Patients older than 40 but younger than 70 years old sometimes benefit from a more intensive follow-up; e.g. when younger than 50 and tumor size >2 cm. The DCE, however, showed that patients chose maximum levels of follow-up independent from age and their individual clinical risk profile. Duration of follow-up and type of consult (either hospital visit or telephone) weighted approximately 0.43 and 0.50 respectively. The frequency of follow-up (either once or twice a year) was least important (0.07). CONCLUSIONS: The model showed that follow-up may be individualized according to risk profile and age. However, patients preferred long and intensive follow-up strategies after breast cancer treatment. Taking into account individual patient preferences it may be recommended to reduce the frequency of follow-up to once a year. The service delivery by nurse practioners is well appreciated and another means for improving cost-effective follow-up.

Obesity and Cancer Treatment: Weighing the Evidence

Obesity rates in the United States have increased tremendously over the past few decades. 1 Obesity is associated with an increased risk of several cancers, including breast cancer, colorectal cancer, and endometrial cancer, and is associated with higher cancer mortality rates. 2,3 Multiple factors contribute to the unfavorable survival rates in obese patients with cancer, including a higher likelihood of comorbid conditions and a higher likelihood of unfavorable tumor characteristics. In addition, systematic underdosing of chemotherapy in overweight and obese patients with breast cancer, 4-7 which occurs in up to 40% of patients, may contribute to the poorer survival rates, particularly among those with estrogen receptor (ER)–negative cancers. 8 This issue of theJournalofClinicalOncology features three studies that broadly address the complicated relationship between weight, factors associated with obesity, and cancer, spanning the bench to the bedside. Creighton and colleagues 9 examined the effect of insulinlike growth factor-2 (IGF-1) exposure on gene expression profiles in MCF-7 breast cancer cells. After developing an IGF-1 gene signature, the investigators assessed the IGF activation score in tumor samples contained within publicly available expression profile databases. The IGF gene signature was associated in this study with other known poor prognostic factors, such as ER-negative status, higher tumor grade, and higher stage. The authors conclude “Transcriptional targets of IGF-1 represent pathways of increased aggressiveness and possibly hormone independence i n... breast cancer.” The findings of this study contribute to our understanding of cancer biology in obese patients, who have higher levels of IGF-1 activity 10 and, in some studies (including the paper by Litton and colleagues in this issue of the Journal 11 ), a higher likelihood of ER-negative breast cancer.

Improved survival for children with parameningeal rhabdomyosarcoma: Results from the AIEOP soft tissue sarcoma committee

Parameningeal rhabdomyosarcoma (PM-RMS) is a rare, highly malignant pediatric tumor arising from locations adjacent to the meninges, from where it can spread intracranially. We reviewed 109 children with non-metastatic PM-RMS enrolled in the Italian RMS79, RMS88 and RMS96 protocols over a 24-year period. All patients received intensive chemotherapy and standard or hyperfractionated and accelerated radiotherapy. Some had delayed surgery. Five-year overall survival rose from 40% in the RMS79 to 72% in the RMS88 and RMS96 protocols (P = 0.01), where more intensive chemotherapy and hyperfractionated accelerated radiotherapy (HART) was used. Delayed surgery after initial treatment was statistically associated with a better prognosis. Unfavorable tumor characteristics for RMS arising in other sites, for example, histology, invasiveness or node involvement, did not predict outcome for PM-RMS. Outcome in PM-RMS patients enrolled in three consecutive Italian protocols has progressively improved, as a result of intensive chemotherapy, delayed surgery and, possibly, HART, though improved imaging and radiotherapeutic tools may have had a role as well.

Elective Nephron Sparing Surgery for Renal Cell Carcinoma Larger Than 4 cm

Elective nephron sparing surgery is established as an alternative to radical nephrectomy for renal cell carcinoma if tumors are small (4 cm or less, stage T1a). We compared outcomes in patients with renal cell carcinoma 4 cm or less (small) vs more than 4 cm (large) who were treated with nephron sparing surgery. Between 1979 and 2006, 618 patients underwent elective nephron sparing surgery at our institution. Of these patients 474 (76.7%) had renal cell carcinoma, which was 4 cm or less in 372 (78.5%) and more than 4 cm in 102 (21.5%). Followup was 4.7 (range 0.1 to 23.9) years for small and 4.7 (range 0.1 to 24.1) years for large tumors. Cancer specific survival and local recurrence free survival were estimated. The estimated cancer specific survival rate at 5 years was 97.9% and 95.8%, and at 10 years it was 94.9% and 95.8% for small and large tumors, respectively (log rank p = 0.583). The survival rate free of local recurrence at 5 years was 98.5% and 98.3%, and at 10 years it was 93.9% and 98.3% for small and large tumors, respectively (log rank p = 0.282). In contrast to tumor size, stage 3 was associated with a significant higher risk of tumor related death. Elective nephron sparing surgery is oncologically safe in select patients with localized renal cell carcinoma more than 4 cm. In our series the selection criterion for choosing elective nephron sparing surgery rather than radical nephrectomy over the years has consistently been safe surgical resectability rather than tumor size. However, there is a correlation between tumor size and unfavorable pathological tumor characteristics, which prompts caution when choosing elective nephron sparing surgery for all large tumors.

Social class is an important and independent prognostic factor of breast cancer mortality

Reasons of the important impact of socioeconomic status on breast cancer prognosis are far from established. This study aims to evaluate and explain the social disparities in breast cancer survival in the Swiss canton of Geneva, where healthcare costs and life expectancy are among the highest in the world. This population-based study included all 3,920 female residents of Geneva, who were diagnosed with invasive breast cancer before the age of 70 years between 1980 and 2000. Patients were divided into 4 socioeconomic groups, according to the woman's last occupation. We used Cox multivariate regression analysis to identify reasons for the socioeconomic inequalities in breast cancer survival. Compared to patients of high social class, those of low social class had an increased risk (unadjusted hazard ratio [HR] 2.4, 95% CI: 1.6-3.5) of dying as a result of breast cancer. These women were more often foreigners, less frequently had screen-detected cancer and were at more advanced stage at diagnosis. They less frequently underwent breast-conserving surgery, hormonal therapy, and chemotherapy, in particular, in case of axillary lymph node involvement. When adjusting for all these factors, patients of low social class still had a significantly increased risk of dying of breast cancer (HR 1.8, 95% CI: 1.2-2.6). Overmortality linked to low SES is only partly explained by delayed diagnosis, unfavorable tumor characteristics and suboptimal treatments. Other factors, not measured in this study, also could play a role. While waiting for the outcome of other researches, we should consider socioeconomic status as an independent prognostic factor and provide intensified support and surveillance to women of low social class.

Racial and Ethnic Disparities in Breast Cancer Mortality: Are We Doing Enough to Address the Root Causes?

Breast cancer is the most common noncutaneous malignancy and the second most lethal form of cancer among women in the United States. Mortality from breast cancer has declined since the late 1980s, but this decline has been steeper among white women compared with black women. As a result, the black:white mortality rate ratio has increased over the last two decades. Other ethnic minorities also suffer from disproportionately high breast cancer mortality rates. This review discusses the causes of racial and ethnic disparities in breast cancer mortality and describes the most common approaches to reducing these disparities. The literature suggests that outcome disparities are related to patient-, provider-, and health system-level factors. Lack of insurance, fear of testing, delay in seeking care, and unfavorable tumor characteristics all contribute to disparities at the patient level. At the provider level, insufficient screening, poor follow-up of abnormal screening tests, and nonadherence to guideline-based treatments add to outcome disparities. High copayment requirements, lack of a usual source of care, fragmentation of care, and uneven distribution of screening and treatment resources exacerbate disparities at the health system level. Although pilot programs have increased breast cancer screening among select populations, persistent disparities in mortality suggest that changes are needed at the policy level to address the root causes of these disparities.

Gender-Related Differences in Outcome for Melanoma Patients

To better understand the factors associated with the well-established gender difference in survival for patients with melanoma. Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood. This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001). Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: A population-based study

There are several treatment alternatives available for patients diagnosed with hepatocellular carcinoma (HCC). Yet, neither the extent to which potentially curative or palliative therapy is used to treat HCC, nor the determinants of using such therapies are known. Further, it is unclear how effective different modalities are for treating HCC. We used the linked SEER-Medicare dataset to identify patients diagnosed with HCC between 1992 and 1999. We identified 2963 patients with continuous Medicare enrollment who were not enrolled in a Medicare-HMO. HCC treatments were categorized as potentially curative therapy (resection, transplant, local ablation), or palliative (trans-arterial chemoembolization (TACE), chemotherapy), and no therapy. Demographic (age, sex, race, geographic region), clinical (comorbidity, risk factors and severity of liver disease) and tumor factors (tumor size, extent of disease) were examined as potential determinants of therapy, as well as survival in univariate and multivariable analyses. Survival curves were also generated and compared among the different treatment modalities. The median age at diagnosis was 74 years (range: 32-105), and most patients (91%) were older than 65 years. Approximately 68% were White, 10% Black, 4% Hispanic, 8% Asian, and 9% were of other race. Thirteen percent of the patients received potentially curative therapy (transplant 0.9%, resection 8.2%, local ablation 4.1%), 4% received TACE, 57% received other palliative therapy, and 26% received no specific therapy. Only 34% of 513 patients with single lesions, and 34% of 143 patients with lesions <3.0 cm received potentially curative therapy. However, 19.2% of patients with unfavorable tumor features (lesion >10.0 cm) received such therapy. Among patients who received potentially curative therapy (n=392), resection was the most common procedure (n=243, 62%) followed by local ablation (n=122, 31%) and finally transplantation (n=27, 7%). In regression analyses, geographic variations in the extent and type of curative therapy persisted after adjusting for demographic, clinical, and tumor features. Median overall survival was 104 days following HCC diagnosis with the longest survival in the transplant group (852 days) and the shortest survival in the group with no treatment (58 days). In the survival analysis, transplantation led to the longest survival, followed by resection. Neither ablation nor TACE yielded prolonged survival (3 year survival was less than 10%). In this predominantly 65 years and older Medicare population, there are marked geographic variations in the management of HCC that seem to be at least as important as clinical and tumor-related features in determining the extent and type of HCC therapy. There is underutilization of potentially curative therapy, even among those with favorable tumor features.

Special issues related to the adjuvant therapy in very young women

A small minority of breast cancer patients consists of young women (<40 years: <6%). Thus, they may not be properly represented in clinical trials. They present with unfavorable tumor characteristics, but young age is an independent negative prognosticator: age is a surrogate for biological mechanisms determining an aggressive cancer phenotype. In premenopausal patients with estrogen receptor-positive (ER+) tumors, adjuvant ovarian function suppression (OSF) was as effective as chemotherapy in ten randomized clinical trials. Chemotherapy reduces the risks of recurrence and death irrespective of endocrine responsiveness of the tumor; however, in patients with ER+ tumors this might result in chemotherapy-induced menopause. Accordingly, OFS did not prolong survival in addition to chemotherapy in meta-analyses and recent clinical trials except in subgroups of particularly young women. Adjuvant tamoxifen is efficient in premenopausal patients with ER+ tumors irrespective of age and the use of chemotherapy. Clinical trials addressing the role of OFS are underway, and future trials should be planned so that the population of young women can be properly analyzed.

Does oncologic specialization influence outcomes following surgery in early stage adenocarcinoma of the endometrium?

Objective. To evaluate treatment outcomes in women with early-stage endometrial cancer (FIGO IA, IB, IC, or IIA) surgically managed by a general gynecologist (GYN) or a gynecologic oncologist (GYO). Methods and results. 349 women treated from 1990–2003 were studied. Median follow-up was 3.7 years. Ninety-five were classified as high-intermediate risk (HIR: stages IB grade III, IC grade II or III, any stage IIA). 110 women received adjuvant radiotherapy. The GYO group had more unfavorable tumor characteristics based on stage and grade ( P < 0.0001), shorter follow-up (median 3.1 vs. 5.1 years, P = 0.0002), and an absolute 12% less likelihood of receiving adjuvant radiotherapy ( P = 0.04). Local and distant failures were not significantly different. Overall survival favored GYN patients ( P = 0.02) with no difference in disease-specific survival ( P = 0.38). Multivariate analysis for disease-free survival revealed HIR disease ( P = 0.04) and GYO treatment ( P = 0.049) to be significant, with a trend for age ≤64 ( P = 0.05). Multivariate analysis for overall survival found age ≤64 ( P = 0.0001), HIR disease ( P = 0.01), and adjuvant radiotherapy ( P = 0.0055) to be significant. Conclusions. Women primarily managed by a GYO for early-stage disease were significantly less likely to receive adjuvant radiotherapy. Despite significantly more unfavorable disease characteristics among GYO-managed women, disease-free and cause-specific survival were equivalent between the two groups. Favorable disease characteristics and adjuvant radiotherapy correlated with improved survival on multivariate analysis.

Early versus late local recurrences after conservative treatment of breast carcinoma. Are there differences in primary tumor characteristics

To investigate whether some aspects of patient or tumor characteristics influence the timing of local recurrence in breast cancer treated conservatively. A retrospective analysis was conducted on patients treated with conservative breast surgery followed by radiotherapy for breast carcinoma, and who developed local recurrence. Out of 2037 cases treated in our Institute, 59 local recurrences were observed within 36 months after treatment, called early local recurrence (ELR), and 87 local recurrences occurred after 60 months, called late local recurrence (LLR). Patient and tumor characteristics were analyzed in the 2 groups and compared. In patients with ELR, the mean age was 53, versus 54 in patients with LLR (ns). Likewise, the menopausal status was evenly distributed in the 2 groups. Primary tumors greater than 20 mm were more frequently found in patients with ELR: 35% vs. 19% in patients with LLR (p = 0.03). Grade 3 tumors were more encountered in patients with ELR: 35% vs. 8% in patients with LLR (p < 0.0001). Tumor ploidy was evenly distributed within the 2 groups. Patients with ELR had tumors with negative estrogen receptors more frequently than patients with LLR: 42% vs. 19% (p = 0.006), and negative progesterone receptors more frequently than patients with LLR: 54% vs. 22% (p = 0.0003). There was no statistically significant difference in the axillary lymph node (LN) status between patients with ELR and those with LLR: respectively 37% and 27% of positive LN (p = 0.18). The specific mortality was higher in patients with ELR: 63% vs. 24% for patients with LLR (p < 0.0001). Unfavorable tumor characteristics as big size, high grade, lack of hormone receptors, but not lymph node status were associated with ELR. The first 3 factors are often linked to tumor cell kinetics. These findings suggest that patients with such aggressive tumor characteristics who do not recur early will have a lower risk of LLR than patients with more favorable factors

PROSTATE CANCER DETECTION IN THE PROSTATE SPECIFIC ANTIGEN RANGE OF 2.0 TO 3.9 NG/ML: VALUE OF PERCENT FREE PROSTATE SPECIFIC ANTIGEN ON TUMOR DETECTION AND TUMOR AGGRESSIVENESS

We evaluated the positive predictive value and cancer detection rate in the prostate specific antigen (PSA) range of 2.0 to 3.9 ng/ml and assessed the value of percent free (F) PSA (FPSA) on tumor detection and tumor aggressiveness in this low PSA range. Of 3623 men who were attending the second round of screening within the European Randomized Study of Screening for Prostate Cancer, section Rotterdam 883 had PSA values of 2.0 to 3.9 ng/ml. These men were offered laterally directed sextant biopsy. FPSA was prospectively determined from pretreatment serum. Cancers were classified as prognostically favorable and unfavorable using biopsy results and other pretreatment diagnostic features. Using the PSA range of 2.0 to 3.9 ng/ml as a biopsy indication 126 cancers were detected, resulting in a positive predictive value of 17.1% and a cancer detection rate of 14.3%. By using percent FPSA and setting relative sensitivity at 95% 9% of biopsies could have been avoided. Unfavorable tumor characteristics were found in 46.9% of the men with T1C tumors. Mean percent FPSA was significantly lower in such men compared to men with favorable tumor characteristics. Of the men with percent FPSA lower than 10% 90% had unfavorable tumor characteristics. The PSA range 2.0 to 3.9 ng/ml is accessible for prostate cancer screening. Percent FPSA is of moderate value in avoiding unnecessary biopsies in the PSA range of 2.0 to 3.9 ng/ml. However, when assessing tumor aggressiveness in biopsy results, percent FPSA is predictive and can be used to select treatment options, such as watchful waiting.

Is information from axillary dissection relevant to patients with clinically node-negative breast cancer?

The changing trends in the diagnosis and management of women with invasive breast cancer have prompted an examination of the need for routine axillary lymph node dissection (ALND) in women with a clinically negative axilla. The objective of this study was to examine the value of information from an ALND in guiding the selection of adjuvant systemic therapy for women with clinically node-negative breast cancer. Between January 1996 and June 2000, 447 clinically node-negative women underwent an ALND as part of their treatment for invasive breast cancer at Westmead Hospital. Three categories of risk of recurrence were devised, based on the primary tumor characteristics alone, without information from an ALND. Recommendations for adjuvant systemic therapy with and without information from an ALND were compared, and the frequency of change was calculated. Overall, 12% of women had their treatment recommendation altered by their pathologic nodal status based on the model treatment algorithm. For women in the low-risk category (pathologic tumor size </=10 mm, grade 1, lymphovascular invasion [LVI] negative, and estrogen receptor [ER] positive), 17% of those less than 50 years old and 14% of those 50-69 years old would have a shift in their treatment recommendations based on the pathologic nodal status. In addition, 13% of the women less than 50 years old and 10% of those 50-69 years old were recommended for more intensive chemotherapy on the basis of four or more involved nodes. For women in the high-risk category (pathologic tumor size greater than 20 mm or greater than 10 mm associated with any unfavorable prognostic factor [grade 3, LVI, or negative ER]), 19% of those less than 50 years old and 18% of those 50-69 years old were recommended for more intensive chemotherapy. Information from ALND did not alter the treatment recommendation for women >/=70 years old, as they were not recommended chemotherapy in the model algorithm. If women >/=70 years old who were node positive and had an ER-negative tumor were recommended chemotherapy, 14% in the high-risk category would have had their treatment recommendation altered as a result of the information from ALND. The continued utilization of ALND is appropriate in women less than 70 years old in the high-risk category. In other patients less than 70 years old, the pathologic nodal status is of value in guiding the selection of women for adjuvant systemic therapy. For women >/=70 years old, information from an ALND adds little to the selection of patients for adjuvant systemic therapy. However, in selected patients >/=70 years old who are classified as high risk on the basis of unfavorable primary tumor features, and are potential candidates for chemotherapy, an ALND would be appropriate.

Adjuvant hormone therapy after radiation or surgery for localized or locally advanced prostate cancer.

Prostate cancer is being diagnosed at an earlier age and earlier disease stage than previously and increasing numbers of relatively young men are receiving potentially curative radical prostatectomy or radiotherapy for early prostate cancer. Although many of these men have an excellent outcome, a significant proportion subsequently experience disease recurrence or cancer-related death. Men with unfavorable tumor characteristics at the time of radical prostatectomy or radiotherapy are particularly at high risk of experiencing disease recurrence. One strategy to improve outcome for these men is adjuvant hormone therapy (hormone therapy administered immediately after therapy of primary curative intent). Surgical castration (bilateral orchiectomy), medical castration using the luteinizing hormone-releasing hormone (LHRH) agonist goserelin, and antiandrogen monotherapy have been investigated as adjuvant hormone therapy to radical prostatectomy and radiotherapy, and each therapy has demonstrated clinical benefits because of a significant improvement in disease-free survival. Furthermore, data are available to indicate that adjuvant hormone therapy achieved by goserelin or bilateral orchiectomy improves overall survival, particularly in men at high risk of progression. Because the effects of LHRH agonists are reversible, they provide a more acceptable method of adjuvant therapy compared to bilateral orchiectomy, particularly in the adjuvant setting, and are preferred by patients. However, the adverse effects on quality of life, in particular on sexual interest and function and bone mineral density, may limit the use of LHRH agonists in some patients. However, these parameters are maintained with nonsteroidal antiandrogens. The first data from the Early Prostate Cancer program indicate that adjuvant bicalutamide 150 mg is associated with a significant improvement in progression-free survival after radical prostatectomy or radiotherapy. Gynecomastia and breast pain are the most common side effects associated with bicalutamide therapy. Medical or surgical castration in combination with an antiandrogen (combined androgen blockade) is another option for use as an adjuvant hormone therapy. However, no study has reported on the use of combined androgen blockade in this setting. Adjuvant hormone therapy provides clinicians with another treatment option for patients with early prostate cancer and unfavorable tumor characteristics.

Lung tumor markers of cytokeratin origin: an overview

Lung tumor markers fall into several categories including oncofetal proteins, structural proteins and their fragments, enzymes, membrane antigens, peptide and non-peptide hormones. Cytokeratins (CK) are well known structural proteins whose degradation gives rise to soluble fragments, measurable in the blood of patients and capable of cancer marking. Among them, Tissue Polypeptide Antigen (TPA), Tissue Polypeptide-Specific Antigen (TPS) and Cytokeratin-19-Fragments (Cyfra 21-1) are the most studied CK fragments' complexes. This article will review biological characteristics and clinical properties of these substances, emphasizing as their concentration in the peripheral blood might reflect the mass of tumor, the rate of cancer cell lysis, and other potentially unfavorable tumor characteristics. Assaying the concentration of CK fragments in the blood is an easy and effective way to assess lung cancer and monitor its clinical evolution.

Treatment of hepatocellular carcinoma by percutaneous laser hyperthermia

The majority of patients with hepatocellular carcinoma (HCC) are unsuitable for partial liver resection or transplantation because of unfavorable tumor characteristics or underlying severe liver disease. Techniques of in situ tumor ablation may be an alternative to resection and have the advantage of reduced morbidity and mortality. Percutaneous laser-induced hyperthermia produces predictable areas of tumor necrosis with minimal complications. This study assesses the effectiveness of percutaneous interstitial laser hyperthermia in eight patients with hepatocellular carcinoma occurring on a background of chronic liver disease. Patients with confirmed HCC with less than five tumor nodules of less than 7 cm maximum diameter were selected for treatment. Tumor response was monitored by dynamic CT, alpha-fetoprotein levels and liver function tests. Patients were discharged within 24 h. There were six males and two females, with liver disease of Child-Pugh grade C in five, and grade B in the others. Two patients had tumor recurrence following previous segmental resection. Four had solitary lesions, and individual lesion size ranged between 3 and 7 cm. Avascularity and significant necrosis of the tumor was achieved on all lesions less than 4 cm, but was unsuccessful in tumors greater than 5 cm despite repeated treatments. Survival of patients ranged from 3 to 18 months. Percutaneous laser hyperthermia produces significant tumor necrosis and has the advantage of low morbidity, and cost effectiveness. Further refinement is needed to achieve elimination of viable tumor cells at the tumor host interface by further knowledge of appropriate dosimetry levels, manipulation of blood flow and synergistic effects with other therapeutic modalities.