Adherence to capecitabine in preoperative treatment of stage II and III rectal cancer: do we need to worry?

BackgroundPreoperative oral capecitabine plus radiotherapy has been progressively adopted in oncology units to provide more convenient care to patients with rectal cancer, but little is known about adherence to this therapy.Patients and methodsProspective, multicentre observational study in six hospitals in metropolitan Barcelona (Spain), in patients with stage II and III rectal cancer. Assessment of adherence was based on the medical report in the clinical history, a patient questionnaire and a pill count in the pharmacy service upon finalization of treatment. Patients were considered adherent if they had taken 80%–110% of the prescribed treatment. We evaluated clinical variables, adverse effects, anxiety and depression (using the hospital anxiety depression scale [HADS]), and quality of life (EORTC QLQ-30). We analysed adherence-associated variables using a logistic regression model and concordance between adherence measures by means of the modified Kappa index.ResultsWe included 119 participants. Adherence measures showed little concordance between the assessment methods used: adherence was 100% according to the clinical history, 83.2% according to self-report and 67.9% according to the pill count. In the multivariable analysis, the most relevant variable associated with non-adherence was anxiety prior to treatment (adjusted odds ratio [ORa] 6.96, 95% confidence interval [CI] 1.48–32.7). We did not observe any relevant association between adherence and clinical variables and baseline quality of life parameters.ConclusionsAdherence to short-term oral neoadjuvant treatment in rectal cancer may be a clinical problem, and it should be acknowledged and systematically evaluated by clinicians during treatment. The limited concordance between different measures of adherence highlights the challenges in monitoring it and the need to use different approaches to assess its impact in clinical practice.     

Is screening for prostate cancer with prostate specific antigen an appropriate public health measure?

Screening and treatment for prostate cancer is controversial. In the absence of randomized trials, several prominent medical organizations in the United States and Europe have formulated policies that range from enthusiastic support to significant skepticism concerning the efficacy of screening and subsequent treatment for prostate cancer. Sharp rises in the incidence of prostate cancer have occurred whenever PSA testing has been introduced on a wide scale. Unfortunately, it is unclear whether declines in prostate cancer mortality can be attributed to PSA testing. Other explanations include the early use of anti-androgen therapy or changes in environmental factors such as diet. Repeated testing for serum PSA has produced significant shifts in the types of cases being identified and has raised the possibility of significant over-diagnosis of this disease. The European screening trial and the PLCO trial in the US will hopefully provide some insights into the value of population-based testing.     

Radical cystectomy: do we need standardization?

Introduction: The first series of radical cystectomy with a definition of surgical landmarks was published in 1949 and was characterized by a high perioperative mortality and a 5-year survival rate around 50%. Decades later, nevertheless many surgical progresses were made and the perioperative mortality dropped to 2,5%, this had not lead to an improvement of long term survival rates, also because a standardization of the procedure is still missing.

Areas covered: Radical cystectomy is performed with different surgical techniques obmitting a standardization. The comparability of many studies is therefore difficult or havely compromised. A paragon with other diciplines was made emphazing that there high surgical quality is defined, measured and controlled. A systematic literature search was made selecting finally 76 article adressing this issue.

Expert commentary: Surgical guidelines in uro-oncology are vague and a definition of surgical quality is missing. A view outside of the box could be very helpful. This is a plea for a change.     

Psychosocial determinants and outcomes of chemotherapy in older women with breast cancer: what do we know? What do we need to know?

With the aging of the U.S. population and rising breast cancer incidence with advancing age, the absolute number of women aged 65 years and older diagnosed with and surviving breast cancer will dramatically increase over the coming decades. Despite this demographic imperative, we know little about the impact of adjuvant therapies in this age group. We synthesized data to describe key findings and gaps in knowledge about the outcomes of adjuvant breast cancer treatment in women aged 65 years and and older ("older women"). We reviewed research published between 1995 and June 2005 on breast cancer outcomes among older women treated with adjuvant therapy for breast cancer. Outcomes included communication, emotional distress, satisfaction, and multiple quality-of-life domains. Only 16 articles focused exclusively on older women and chemotherapy; and only one included a large sample of older women (N = 1755). Most common domains included comorbidities, symptoms, and survival. Of the 13 clinical trials and three observational studies we reviewed, only one clinical trial measured quality of life and psychological factors such as coping. None of the studies examined patient preferences or patient-physician communication (processes of care) in older women. Few studies have been designed to specifically evaluate adjuvant therapy processes and outcomes among older women, especially interactions between treatment and comorbidity, and the impact of the processes of care on outcomes. In addition, only narrow segments of the older population with breast cancer (e.g., well-educated, nonminority women) have been included in trials to date. Thus, at present we do not have sufficient data to assist physicians and their older patients in developing adjuvant treatment decisions and plans tailored to older women's needs, preferences, and concerns.     

Economical data and advanced prostate carcinoma: do we need new guidelines for decision making?

Based on epidemiological data of incidence, estimated prevalence of advanced prostate carcinoma in Germany, and the cost of androgen deprivation of different regimens were determined in a study model. We analyzed data, published by the Tumor Registry of Munich, which indicate that from 3,838 patients with carcinomas of the prostate, 38% has been treated exclusively with hormone suppression therapy, 14% of patients had undergone a combined radiation therapy and hormone suppression therapy and 9% underwent combined surgical therapy and hormone suppression therapy. The mean survival time of patients treated with medical therapy alone, for patients treated with combined radiation therapy and medical therapy were 60, 24, and 120 months, respectively. The cost for orchiectomy was estimated as $1,072, and for LH-RH therapy as $224/month. We estimated an incidence of 17,700 (per year) and a prevalence of 115,000 patients with advanced prostate cancer for Germany. Provided all patients received LH-RH treatment a total cost of $308,000,000/year would arise. Provided, all patients underwent surgery a total cost of $19,000.000/year would arise. If all patients received LH-RH agonists, the treatment would amount to $16,944 per patient, independently of the prognostic group; and for surgery $1,072 per patient would arise. Limited health care budgets mandate critical determination and evaluation of costs to provide a component for the complex decision making process. However, they must be complimented by validated data of quality of life, which can than be a basis for new guidelines of decision making.     

Can initial prostate specific antigen determinations eliminate the need for bone scans in patients with newly diagnosed prostate carcinoma? A multicenter retrospective study in Japan

BACKGROUND: The objective of the current study was to assess rigorously whether serum prostate specific antigen (PSA) determination can eliminate the need for bone scans in Japanese patients with newly diagnosed prostate carcinoma with serum PSA levels < or = 10 ng/mL. METHODS: A retrospective assessment of 1294 patients with newly diagnosed, untreated prostate carcinoma was conducted at the authors' institutions. All patients underwent a bone scan, serum PSA measurement, and core needle biopsy of the prostate. The receiver operating characteristic curve for identifying a positive bone scan based on serum PSA levels and a decision tree were analyzed to determine the expected 10-year cumulative cost and disease specific survival rate. Two competing strategies were used: PSA alone and PSA plus baseline bone scan. For the PSA-alone strategy, a baseline bone scan was performed only when the patient had a serum PSA level > 10 ng/mL. RESULTS: The proportion of positive bone scans in patients with serum PSA levels < or = 10.0 ng/mL was 1.33%. The area under the receiver operating characteristic curve was 0.870. Patients with a Gleason Grade > or = 3 tumors or with a Gleason score > or = 7 had a higher proportion of positive bone scans. The 10-year disease specific survival rates with the PSA-alone strategy and the PSA-plus-bone-scan strategy were the same. The PSA-alone strategy was minimally cost effective, with a savings of $16.00 (U.S.) in the cumulative net cost per patient over the PSA-plus-bone-scan strategy. CONCLUSIONS: The current results suggest that baseline bone scans can be eliminated in patients with newly diagnosed prostate carcinoma in Japan who have serum PSA levels < or = 10 ng/mL. Apparently, it is possible to omit baseline bone scans for patients with a Gleason Grade < or = 2 tumors or with a Gleason score < or =6.     

Prognostic factors in chronic lymphocytic leukemia-what do we need to know?

Of all leukemias, chronic lymphocytic leukemia (CLL) shows the highest variability in its clinical presentation and course. CLL can present as an aggressive and life threatening leukemia or as an indolent form that will not require treatment over decades. The currently available clinical staging systems for CLL are simple and inexpensive but lack accuracy to predict disease progression and survival on an individual basis. The increased understanding of the key events of molecular pathogenesis has provided a plethora of novel molecular and biological factors that correlate with the outcome of CLL. This Review provides a concise discussion of the most important discoveries and gives guidance on how to implement novel prognostic tools in the clinical management of CLL by applying the criteria of evidence, relevance, and simplicity to the selection of prognostic markers.     

A whole systems research approach to cancer care: why do we need it and how do we get started?

Because cancer care is presently developing into a complicated network of interventions delivered at different times and places with different intentions, there is a need to consider whether the current research approaches in clinical cancer care adequately cover the ongoing treatment choices and combinations. Researchers in complementary and alternative medicine (CAM) are proposing whole systems research as an additional research approach for modern systems of care, whether they include complementary and alternative medicine or not. The current status of whole systems research methodology development is mainly theoretical. Necessary components of the methodology include focus on interventions, context, process, outcomes, and philosophy. Further development should be based on observational studies using both qualitative and quantitative approaches, often combined. Only when modern healthseeking systems of treatment behaviors are thoroughly understood should fine-tuning of hypothesis-testing research methods be continued.     

Prostate cancer diagnosis: should patients with prostate specific antigen >10 ng/mL have stratified prostate biopsy protocols?

Background: Trans-rectal ultrasound (TRUS) guided systematic prostate biopsy is a standard tool in prostate cancer (CaP) diagnosis. Extended biopsy techniques using 10-12 cores are the norm. Controversy exists on extended TRUS biopsy in men with PSA >10 ng/mL. We evaluated cancer detection rates on an individual core basis, to stratify prostate biopsy protocols based on PSA levels. Patients and methods: Over a five-year period, 1036 patients underwent TRUS guided prostate biopsy for raised serum PSA (>2.5 ng/mL). 436 patients had PSA >10 ng/mL. Patients with PSA <50 ng/mL underwent a 12-core TRUS guided prostate biopsy including six peripheral biopsies. The six peripheral biopsies were directed laterally towards the base, mid-zone and apices. Remainder were standard para-sagittal sextant biopsies. Patients were stratified into three groups (PSA 10-20 ng/mL, 20-50 ng/mL and >50 ng/mL). Results: Mean age of 436 patients with PSA >10 ng/mL was 70.3years. 270 (62%) men had cancer. Cancer detection rates for different PSA levels were 46% (10-20 ng/mL), 76% (20-50 ng/mL) and 93% (>50 ng/mL). Higher PSA levels and advanced clinical stage were associated with increased cancer detection rates. All patients with clinical T3 and T4 disease had biopsy diagnosed CaP. Conclusion: TRUS guided prostate biopsy in patients with PSA >10 ng/mL did not require 12 cores to diagnose CaP. CaP diagnosis required 8 cores in men with PSA 10-20 ng/mL. These cores were right and left peripheral basal and apical, and right and left para-sagittal basal and apical biopsy. Only 6 cores were necessary to diagnose CaP in men with PSA >20 ng/mL which were right and left peripheral basal and apical, and para-sagittal apical biopsies. We suggest limited TRUS prostate biopsy protocols for men with PSA >10 ng/mL.     

Prostate specific antigen: a useful screening test?

The role of prostate specific antigen (PSA) as a screening test for prostate cancer is controversial. Proponents of screening emphasize that early detection can lead to discovery of organ-confined disease and the potential for cure. Opponents point to the lack of credible evidence that screening is associated with a decrease in mortality. In addition, population-based screening (with subsequent diagnosis and treatment in many men) can be associated with considerable morbidity and mortality in the context of a disease that is often not fatal. This report examines the limitations of PSA as a screening test and supports an approach using "verbal informed consent" to identify patients who should be tested.     

Use of radiomics in the radiation oncology setting: Where do we stand and what do we need?

Radiomics is a field that has been growing rapidly for the past ten years in medical imaging and more particularly in oncology where the primary objective is to contribute to personalised and predictive medicine. This short review aimed at providing some insights regarding the potential value of radiomics for cancer patients treated with radiotherapy. Radiomics may contribute to each stage of the patients’ management: diagnosis, planning, treatment monitoring and post-treatment follow-up (toxicity and response). However, its applicability in clinical routine is currently hindered by several factors, including lack of automation, standardisation and harmonisation. A major effort must be carried out to automate the workflow, standardise radiomics good practices and carry out large-scale studies before any transfer to daily clinical practice.     

Aggressive variants of prostate cancer – Are we ready to apply specific treatment right now?

Recently, adoption of novel drugs for systemic treatment of metastatic prostate cancer has led to a striking improvement of response rate and survival in both hormone-sensitive and castration-resistant disease. In most cases, prostate cancer essentially depends on androgen receptor signaling axis, even in castration-resistant setting, and hence may be targeted by second generation hormonal therapy. However, a subset of patients bears androgen-independent cancer biology with a short-term response to hormonal treatment, early and extensive visceral metastases, low PSA levels and poor outcomes. Identification and specific management of these rapidly fatal malignancies is of an unmet medical need since their classification and utilized therapeutic regimens vary significantly. Unfortunately, molecular pathways have not been sufficiently elucidated yet in order to provide an effective targeted treatment with a prolonged response. Lack of diagnostic and predictive biomarkers for these cancers makes successful counteractions against them even more sophisticated. In this comprehensive review, we aimed at summarizing the current body of literature reporting on causal molecular machinery as well as diagnostic and therapeutic concepts of aggressive prostate tumors and draw clinically relevant conclusions for the up-to-date sensible disease management.     

Cord stem-cell transplantation in Ontario: do we need a public bank?

It has been 21 years since the first successful use of umbilical cord blood as a source of donor cells for hematopoietic stem cell transplantation (HSCT). Over those years, cord blood transplantation (CBT) has shown marked success as an effective modality in the treatment of children and adults with hematologic malignancies, marrow failure, immunodeficiency, hemoglobinopathy, and inherited metabolic diseases. Furthermore, transplantation without full human leukocyte antigen (HLA) matching is possible and, despite a lower incidence of graft-versus-host disease, graft-versus-leukemia effect is preserved. More than 20,000 cbts have been performed worldwide. Ontario is the most populated province in Canada, and its cbt numbers have increased dramatically in recent years, but most of the umbilical cord blood units are purchased from unrelated international registries. There is no public cord bank in Ontario, but there is a private cord banking option, and notably, Ontario has the largest number of live births in Canada [approximately 40% of all Canadian live births per year occur in Ontario (Statistics Canada, 2007)]. In this brief review, the pros and cons of private and public cord banking and the feasibility of starting an Ontario public cord bank are discussed.     

Prostate specific antigen as a clinical biomarker for prostate cancer: what's the take home message?

Prostate specific antigen (PSA) continues to be challenged as a legitimate clinical biomarker in early detection of prostate cancer due to lack of specificity for malignant transformation. Skepticism surrounding the utility of serum PSA as a clinical marker is not new and many questioned its initial use in widespread prostate cancer screening due to non-specific expression and low predictive value for cancer detection. Despite these initial concerns, serum PSA measurement along with digital rectal examination (DRE) is currently the accepted practice for prostate cancer screening in the United States with hundreds of thousands of men undergoing serum PSA measurement annually. In contrast to its role for early detection, serum PSA measurement as a surrogate for prostate cancer recurrence (biochemical failure) following curative intent therapy has consummate clinical utility in post-treatment surveillance. As thousands of men each year are aggressively treated for potentially curable prostate cancer, development of simple and effective diagnostic tools for detecting treatment failures should be an important area of biomedical and clinical investigation. We have constructed and tested a home-based prostate cancer surveillance device for use by patients to detect PSA from blood obtained by finger stick. Our initial results suggest that home based PSA testing is feasible and may have clinical utility in management of men treated for prostate cancer.