When and how should surgery be performed in senior colorectal cancer patients?

Older studies reported high rates of postoperative morbidity and mortality in the senior population, which lead to a tendency to withhold curative surgery in the older population. However, more recent studies showed impressing developments in postoperative outcomes in seniors. Probably, these improvements are due to enhancements in both surgical and non-surgical aspects in the pre-, peri- and postoperative period, such as minimally invasive techniques and anesthesiological insights. The postoperative survival gap seen earlier between younger and older patients is fading. For optimal treatment in the older population, special awareness and care on several aspects is needed. As only a minority of the seniors are frail, a quick frailty assessment is crucial to distinguish the fit from the frail in the decision-making process. In addition, it could be valuable to improve the lacks in physical condition in the preoperative period with the use of prehabilitation programs. Furthermore, it is important to evolve an emergency to an elective setting by postponing emergency surgery to prevent any high-risk situation. In conclusion, based on modern insights, surgery is a valid option in the curative treatment of colorectal cancer in seniors, however individual attention and care is required.     

Quality of life assessments in advanced breast cancer: should there be more consistency?

REED E., KÖSSLER I. & HAWTHORN J. (2012) European Journal of Cancer Care 21 , 565–580 Quality of life assessments in advanced breast cancer: should there be more consistency? Quality of life (QOL) measures have assumed increasing importance in assessing the impact of therapeutic drugs and interventions on patients and in making judgements about their cost‐effectiveness. Important treatment decisions and crucial funding strategies involve QOL data and, for patients with a disease such as advanced breast cancer that impinges on their life expectancy, QOL can become a hugely important consideration. Yet, despite this, there is a lack of consensus on what defines an appropriate QOL measure, and inconsistency in the instruments that are chosen to measure it. The National Institute for Health and Clinical Excellence (NICE) is seen as a model for appraising the value of new treatments and NICE approval is required for treatments to be funded in the UK. In order to compare different disease conditions they use a generic measure, preferring the EQ‐5D. We have performed a literature search of clinical trials in advanced breast cancer to establish which QOL measures have been used. Our findings show marked heterogeneity in terms of which QOL tools are used. It is suggested that there should be more consensus on which QOL instruments are used, not only between researchers, but between them and the bodies that approve funding.     

When should trastuzumab be stopped after achieving complete response in HER2-positive metastatic breast cancer patients?

We report the case of a woman with HER2-positive metastatic breast cancer who achieved prolonged complete remission of multiple liver metastases after treatment with weekly trastuzumab plus paclitaxel but relapsed in the brain soon after stopping trastuzumab maintenance therapy which had been prosecuted for almost three years. In the absence of randomized trials, the optimal duration of trastuzumab administration after achieving complete remission of metastatic breast cancer remains questionable.     

Who should be included in a clinical trial of screening for bladder cancer?

BACKGROUND:

Because of its relatively low incidence, bladder cancer screening might have a better ratio of benefits to harms if it is restricted to a high‐risk population. Data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were used and simple decision analytic techniques were applied to compare different eligibility criteria for a screening trial.

METHODS:

For a variety of possible eligibility criteria, the percentage of the population aged 55 years to 74 years and classified as being at high risk for developing invasive or high‐grade carcinoma, and therefore likely to benefit from screening, was calculated. Regression models were used to calculate a risk score based on age, sex, smoking history, and family history of bladder cancer. The reduction in cases was calculated given hypothetical risk reductions associated with screening. The trade‐off between patients screened and tumors avoided was calculated as a net benefit.

RESULTS:

The 5‐year probability of being diagnosed with invasive bladder cancer was 0.24%. Using a risk score > 6 or > 8 as the eligibility criterion for a trial was generally superior to including all older adults. In a typical scenario, a risk score > 6 would result in approximately 25% of the population being screened to prevent 57 invasive or high‐grade bladder cancers per 100,000 population; screening the entire population would prevent only an additional 38 cases.

CONCLUSIONS:

Screening for bladder cancer can be optimized by restricting it to a subgroup of patients considered to be at elevated risk. Different eligibility criteria for a screening trial can be compared rationally using decision‐analytic techniques. Cancer 2013. © 2012 American Cancer Society.     

Breast cancer in elderly women: Can radiotherapy be omitted?

It is tempting to spare elderly women the burden of adjuvant radiotherapy after breast cancer surgery, even if such a treatment would be justified in light of the available clinical evidence. The reason is that evidence-based radiotherapy derives from clinical trials that excluded elderly women, and that breast cancer is often believed to be more indolent at advanced ages. Unfortunately, the epidemiological evidence, and the few clinical trials recruiting patients over 65 or 70 year of age, all point to the need for postoperative irradiation in a similar set-up as in younger patients. So far, there is no evidence that a subgroup exists in which radiotherapy can be safely omitted. Therefore, the decision to treat or not to treat should be openly discussed with the patient, addressing risks and benefits of both attitudes. Only in frail patients, with an obviously limited life expectancy (months or at most a few years), can omission of radiotherapy be considered, as the burden of local recurrence is likely not to appear before the patient dies from an other cause.     

Cervical cancer incidence in elderly women-biology or screening history?

AimIn many countries, the age-specific pattern of cervical cancer incidence is currently bipolar with peaks at for instance 45 and 65 years of age. Consequently, a large proportion of cervical cancer cases are presently diagnosed in women above the screening age. The purpose of the study was to determine whether this bipolar pattern in age-specific incidence of cervical cancer reflects underlying biology or can be explained by the fact that the data come from birth cohorts with different screening histories.MethodsCombination of historical data on cervical screening and population-based cancer incidence data from Denmark 1943–2013, Finland and Norway 1953–2013, and Sweden 1958–2013.ResultsSince the implementation of screening, the incidence of cervical cancer has decreased for each successive birth cohort. All birth cohorts showed a unipolar age-specific pattern. In unscreened women in Denmark and Sweden, the incidence peaked around the age of 50; the peak was less marked in Finland; while peak age for unscreened women could not be determined for Norway due to widespread opportunistic screening. The current old-age peak in the incidence of cervical cancer represents residuals from unscreened or underscreened birth cohorts.ConclusionThe current bipolar pattern in age-specific incidence of cervical cancer can largely be explained by the different screening histories of successive birth cohorts. While it is reasonable to offer screening to elderly women today, birth cohort trends in disease burden should be carefully monitored to justify permanent changes in upper screening age.     

Should radiotherapy be avoided or delivered differently in elderly patients with rectal cancer?

Purpose is to give an overview of treatment possibilities of rectal cancer over time, but also of the real management of rectal cancer especially in relation to age. From literature search representative randomised studies on patients with resectable rectal cancer, comparing only surgery, post- and preoperative radiotherapy with or without chemotherapy, are reviewed. We also reviewed the literature regarding radiotherapy for rectal cancer described in population-based studies. The overview of the trials showed that preoperative radiotherapy improves local control in relation to no or postoperative radiotherapy. Adding chemotherapy did not significantly improve survival. No relations were seen between age and complications. All population-based studies showed that increasing age is associated with less (neo)adjuvant treatment. To avoid local recurrence, the best possible treatment, being preoperative RT, should be given to all patients with resectable rectal cancer, irrespective of age.     

Is endometrial carcinoma intrinsically more aggressive in elderly patients?

BACKGROUND: The current study was conducted to determine the influence of old age (age >/= 70 years) on outcome in a group of patients with endometrial carcinoma who were treated with simple hysterectomy followed by adjuvant radiation therapy (RT). METHODS: Between November 1987 and May 2000, 405 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IB-II endometrial carcinoma were treated with postoperative RT. Intravaginal RT alone was given to 77% of patients (median dose, 21grays [Gy] given in 3 fractions). Additional postoperative external beam radiation therapy (EBRT) was given to 23% of patients (median dose, 45 Gy). Eighty-four patients were age >/= 70 years and 321 patients were age < 70 years. The two groups were well balanced with regard to race, comprehensive surgical staging, aggressive histology, lymphovascular invasion, lower uterine segment involvement, cervical involvement, and the use of postoperative EBRT. Significantly more patients in the age >/= 70 years group had other comorbidities such as obesity, diabetes mellitus, or hypertension (P = 0.02) and were found to have deep (> 50%) myometrial invasion (P = 0.008). RESULTS: With a median follow-up time of 48 months, the 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were 95%, 91%, and 90% respectively. On multivariate analysis, poor LRC was found to be correlated with age >/= 70 years (P = 0.019) and lymphovascular invasion (P = 0.001). Poor DFS was found to be correlated with age >/= 70 years (P = 0.03), lymphovascular invasion (P = 0.01), and aggressive histology (P = 0.001). Similarly, poor OS was found to correlate with age >/= 70 years (P = 0.001), lymphovascular invasion (P = 0.01), aggressive histology (P = 0.01), and cervical involvement (P = 0.02). The same factors that were found to correlate with OS (age >/= 70 years, lymphovascular involvement, aggressive histology, and cervical involvement) also appeared to correlate with disease-specific survival (P = 0.03, P = 0.008, P = 0.001, and P = 0.04, respectively). The 5-year actuarial rates of Radiation Therapy Oncology Group late complications that were >/= Grade 3 (gastrointestinal tract, genitourinary tract, or vagina) were 3% in both groups. CONCLUSIONS: Even when treated in a similar fashion, endometrial carcinoma patients age >/= 70 years appear to fare worse than younger patients independent of other poor prognostic factors. The rate of complications from adjuvant RT, despite a higher rate of comorbidity in elderly patients, was found to be similar in both age groups. Endometrial carcinoma appears to be intrinsically more aggressive in older patients, thus mandating further improvement in their treatment strategies.     

Disclosure of cancer diagnosis and quality of life in cancer patients: should it be the same everywhere?

Background  

Evidence suggests that truth telling and honest disclosure of cancer diagnosis could lead to improved outcomes in cancer patients. To examine such findings in Iran, this trial aimed to study the various dimensions of quality of life in patients with gastrointestinal cancer and to compare these variables among those who knew their diagnosis and those who did not.     

Can cervical cancer screening be stopped at 50? The prevalence of HPV in elderly women

Although the relation between cervical cancer and the human papillomavirus (HPV) has been established beyond doubt, the introduction of HPV detection in cervical cancer screening is halted, primarily by the high rate of false positivity in relation to morbidity, since the majority of women infected with HPV will not develop lesions. To counteract overconsumption of cervical cancer screening in elderly women, we wanted to test the hypothesis that women of 50 years or older who are HPV-negative and have a cytologically normal smear might be encouraged to refrain from further screening. As a first step, the prevalence of high-risk HPV in a population of 1,936 women of 50 years and older was investigated. After an initial decline, a slightly higher prevalence can be seen with increasing age. There is a decrease in the prevalence of multiple infections with age, paralleled by an increase in single infections, especially of HPV type 16 in the eldest-age group. However, neither the decrease in multiple infections nor the increase in single infections is statistically significant. The data obtained in this study show that, even in the presence of a slight increase in the HPV prevalence in elderly women, approximately 94% of the elderly women can be withdrawn from the cervical cancer screening. However, a follow-up study will be necessary to determine the frequency of (re)infection as well as the course of an HPV infection in elderly women.     

Chemotherapy in elderly small-cell lung cancer patients: yes we can,but should we do it?

BackgroundTwenty percent of all newly diagnosed patients with small-cell lung cancer (SCLC) are >75 years. Elderly patients may show more toxicity due to co-morbidity. We evaluated motives for adherence to treatment guidelines, completion of treatment and toxicity.Patients and methodsPopulation-based data from patients aged ≥75 years and diagnosed with SCLC in 1997–2004 in The Netherlands were used (368 limited disease and 577 extensive disease). Additional data on co-morbidity (Adult Co-morbidity Evaluation 27), World Health Organisation performance status (PS), treatment, motive for no chemotherapy, adaptations and underlying motive and grade 3 or 4 toxicity were gathered from the medical records.ResultsForty-eight percent did not receive chemotherapy. The most common motives were refusal by the patient or family, short life expectancy or a combination of high age, co-morbidity and poor PS. Although only relatively fit elderly were selected for chemotherapy, 60%–75% developed serious toxicity, and two-thirds of all patients could not complete the full chemotherapy.ConclusionsWe hypothesise that a better selection by proper geriatric assessments is needed to achieve a more favourable balance between benefit and harm.     

Breast cancer incidence after the introduction of mammography screening: what should be expected?

BACKGROUND: A prevalence peak is expected in breast cancer incidence when mammography screening begins, but afterward the incidence still may be elevated compared with prescreening levels. It is important to determine whether this is due to overdiagnosis (ie, the detection of asymptomatic disease that would otherwise not have arisen clinically). In the current study, the authors examined breast cancer incidence after the introduction of mammography screening in Denmark. METHODS: Denmark has 2 regional screening programs targeting women ages 50 years to 69 years. The programs were initiated in 1991 and 1993, respectively. No screening takes place in the 13 other Danish regions. Data regarding incident breast cancers detected between 1979 and 2001 were retrieved from the Danish Cancer Registry for each screening region and for the rest of Denmark, and time trends in rates for women ages 50 years to 69 years were compared. From 1 program, individual screening data were used to analyze breast cancer incidence in women who were never screened, those who were screened for the first time, or those who previously were screened. RESULTS: The incidence of breast cancer was found to have increased regardless of screening. In the screening regions, a marked prevalence peak was observed, and the incidence hereafter was compatible with the level indicated by the 95% confidence limits for the regression curves for the rates in the prescreening period, taking into account the artificial ageing in the program, the influx of newcomers, and variations in the data. Women who had undergone previous screening were found to have the same incidence of breast cancer as women who were never screened. CONCLUSIONS: The data from the current study do not provide evidence of overdiagnosis of invasive breast cancer in the 2 Danish screening programs or, if overdiagnosis was found to occur, it was only of limited magnitude.     

Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy.     

Colorectal cancer in young patients: is it a distinct clinical entity?

Background

The incidence of colorectal cancer in young patients is increasing. It remains unclear if the disease has unique features in this age group.

Methods

This was a single-center, retrospective cohort study which included patients diagnosed with colorectal cancer at age ≤40 years in 1997–2013 matched 1:2 by year of diagnosis with consecutive colorectal cancer patients diagnosed at age >50 years during the same period. Patients aged 41–50 years were not included in the study, to accentuate potential age-related differences. Clinicopathological characteristics, treatment, and outcome were compared between groups.

Results

The cohort included 330 patients, followed for a median time of 65.9 months (range 4.7–211). Several significant differences were noted. The younger group had a different ethnic composition. They had higher rates of family history of colorectal cancer (p = 0.003), hereditary colorectal cancer syndromes (p < 0.0001), and inflammatory bowel disease (p = 0.007), and a lower rate of polyps (p < 0.0001). They were more likely to present with stage III or IV disease (p = 0.001), angiolymphatic invasion, signet cell ring adenocarcinoma, and rectal tumors (p = 0.02). Younger patients more frequently received treatment. Young patients had a worse estimated 5-year disease-free survival rate (57.6  vs. 70 %, p = 0.039), but this did not retain significance when analyzed by stage (p = 0.092). Estimated 5-year overall survival rates were 59.1 and 62.1 % in the younger and the control group, respectively (p = 0.565).

Conclusions

Colorectal cancer among young patients may constitute a distinct clinical entity. Further research is needed to validate our findings and define the optimal approach in this population.

     

Fatigue in female breast cancer patients: might its origins be more generic than we think?

DE JONG N. (2011) European Journal of Cancer Care 20 , 701–702 Fatigue in female breast cancer patients: might its origins be more generic than we think?     

Oesophageal cancer: How radical should surgery be?

Introduction

Oesophagectomy for carcinoma can be viewed as comprising two components: resection of the oesophagus and resection of the enveloping lymphatics. Controversy exists regarding how extensive these two components should be.

Methods

Through a literature overview, the aim of this educational article is to provide surgeons with arguments to understand which operation is the most oncologically sound according to patient and tumour parameters.

Results

Non-randomised comparative studies evaluating radical lymphadenectomy have reported controversial survival benefit. Independent association found between the number of surgically removed lymph nodes and overall survival is an indirect evidence supporting radical lymphadenectomy. The only phase III trial comparing non-radical transhiatal oesophagectomy with transthoracic oesophagectomy for patients with oesophageal adenocarcinoma found 5-year survival rates of 29% vs. 39%, respectively. Although not statistically significant due to underpowered study, specialists would consider less of an increase in survival to be clinically relevant. For squamous OC, the first small randomised controlled trial comparing 2-field lymphadenectomy to 3-field lymphadenectomy did not found significant 5-year survival difference (48% vs. 66%) and the second one comparing 2-field lymphadenectomy to lymph node sampling identified a survival benefit favoring radical resection (36% vs. 25%).

Conclusion

Radical transthoracic oesophagectomy with two-field lymphadenectomy appears to offer an optimal balance between benefits and risks to a majority of OC patients, especially in the growing area of neoadjuvant treatments. Non-radical resection should be probably reserved for patients with a poor general status whereas 3-field lymphadenectomy may be reserved to selected patients with loco-regional disease in experienced hands, surely for patients with upper OC.     

Should mammographic screening be done in primary ovarian cancer?

Breast cancer is a significant global health problem. It is the most common malignancy in women. Mammographic screening is recommended for women older than 40 yr for early detection of breast cancer. The aim of this study is to evaluate the role of screening mammography in ovarian cancer independent of age. Eighty-four patients with ovarian cancer were evaluated with bilateral mammography. Two hundred asymptomatic healthy controls with a similar age distribution were also imaged with screening mammography. Mammography results were classified according to the American College of Radiology criteria in five groups. The median age of the study group was 51.4 (range, 27–77) and 49.3 (range, 30–75) in the control group. Screening mammography detected four cases of malignancy (4.8%) in patients with ovarian cancer; two were the primary breast carcinomas (2.5%) and two were metastatic cancers from the ovary. Five subjects (2.5%) among healthy controls were also found to have breast cancer. Although the incidence of primary breast carcinoma was found to be similar in the two groups (2.5%), mammographic imaging detected metastatic disease to the breast from the ovaries. Mammography should therefore be considered in patients with ovarian cancer independent of age.