Differences according to socioeconomic status in the management and mortality in men with high risk prostate cancer

Background

Outcomes for many cancer forms are associated with socioeconomic status (SES).We investigated if SES was associated with management and mortality in men with high risk prostate cancer.

Material and methods

A nation-wide population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged database including data on incident prostate cancer identified in the National Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined as T3 tumour, and/or Gleason score 8-10 and/or PSA 20-50 ng/mL. Use of bone scan, curative treatment, and mortality in relation to SES was assessed by logistic, Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period and clinical subgroups.

Results

Amongst 17,522 high risk prostate cancer patients, a bone scan was more often performed in higher white-collar than in blue-collar workers (OR 1.30; 95% CI 1.21-1.40). Amongst men without metastases, the likelihood of intention to treat was higher in higher white-collar workers (OR 1.43; 95% CI 1.28-1.57). In men who received curative treatment, the likelihood was higher to undergo radical prostatectomy for higher white-collar patients (OR 1.29; 95% CI 1.10-1.47). In men without metastases, not only overall mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60-0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49-0.99).

Conclusions

We conclude that socioeconomic disparities in the management and mortality in men with high risk prostate cancer exist also within the setting of a National Health Care System aiming to provide care on equal terms to all residents.     

Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer

Background and purpose

Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer.

Methods

We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months.

Results

We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2-14 years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3-9.7).

Conclusion

Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region.     

Hormonal therapy or external-beam radiation with brachytherapy and the risk of death from prostate cancer in men with intermediate risk prostate cancer

Purpose

To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy.

Patients and Methods

A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer-specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category.

Results

Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively).

Conclusion

Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.     

Couples' communication before the wife's death to cancer and the widower's feelings of guilt or regret after the loss - a population-based investigation

Aim

To investigate the association between couples’ communication before the wife’s death to cancer and the widower’s feelings of guilt and regret after the loss, in a population-based data.

Methods

Men (n = 907) younger than 80 years and living in Sweden, who had lost their wives due to cancer, were asked 4-5 years after their loss to answer an anonymous postal questionnaire it included questions about the couple’s end-of-life communication during the last 3 months of life and the widower’s feelings of guilt or regret during the first 6 months after the wife’s death.

Results

During the last 3 months of their wives’ lives, men who had not talked about the impending death with their wives had a higher risk of experiencing feelings of guilt than men who did talk (relative risk (RR) 2.0, 95% confidence interval [CI] 1.2-3.4). Men who were not able to spend as much time as they wished with their wives had an increase in the risk of having feelings of guilt twice that of men who spent time (RR 2.0 95% CI 1.5-2.7). Men who did not talk with their wives about how they could cope practically or emotionally after the death had elevated risks of guilt feelings compared with men who talked (RR 1.8, 95% CI 1.0-3.0; RR 1.7, 95% CI 1.0-2.9, respectively). Men who realised it was too late to discuss the impending death had an increased risk of guilt feelings (RR 4.3, 95% CI 2.9-6.6). Men who thought that not everything had been brought to closure before their wives’ deaths had 3.3 times increased risk of guilt feeling (RR 3.3, 95% CI 1.7-6.4).

Conclusions

A man who does not have end-of-life discussions with his wife during the last 3 months before her death from cancer may be subject to a significantly greater risk of experiencing feelings of guilt or regret in widowhood than men who did engage in such discussions.     

Parity, early menopause and the incidence of bladder cancer in women: a case-control study and meta-analysis

Introduction

Incidence rates of bladder cancer are notably higher in men than in women. While there is evidence that reproductive and hormonal risk factors may influence risk of bladder cancer, data are inconclusive.

Materials and methods

We examined reproductive, menstrual and hormonal use history in our population-based case-control study of bladder cancer in New Hampshire (NH), USA (n = 207 women cases and n = 463 women controls). Additionally, we performed a meta-analysis of the published literature. We used unconditional logistic regression analysis to compute adjusted odds ratios associated with each risk factor in the NH study. We combined these estimates with those from the published literature using inverse variance effects models.

Results

In the NH study, a slightly decreased odds ratio was found among women who had ever had a birth compared to nulliparous women and an elevated odds ratio among women who underwent surgical menopause (bilateral oophorectomy), especially at an early age. No overall associations were found with oral contraceptive use or hormone replacement therapy. These findings were generally in agreement with the meta-analytic results for which the combined relative risk (RR) estimate was reduced among ever parous women (combined RR estimate for ever parous versus nulliparous = 0.66, 95% confidence intervals [95% CI] 0.55-0.79) and elevated among those undergoing an early menopause (combined RR estimate for early versus late menopause = 1.59, 95% CI 1.31-1.92). No consistent risk was observed for the other factors.

Discussion

Some reproductive and menstrual factors appear to be related to the incidence of bladder cancer among women; but whether effects are due to female hormones is uncertain.     

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: A systematic review

Background and Purpose

For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be given by dose-escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR) brachytherapy (EBTI). Differences in outcome between the modalities were assessed by a systematic review.

Materials and methods

A systematic search was performed resulting in 40 articles to be used. Data were extracted on biochemical control and overall survival at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. Comparison of the modalities was done by a Weibull survival analysis and estimation of Hazard Ratio’s (HR) was done with 95% confidence intervals (95% CIs).

Results

The HR for biochemical recurrence was 1.40 (95% CI 1.31-1.51) for EBRT relative to EBTI, and was 1.37 (95% CI 1.26-1.49) for EBSeeds relative to EBTI. The HR for overall survival was 1.50 (95% CI 1.29-1.73) for EBRT relative to EBTI, and was 2.33 (95% CI 2.04-2.66) for EBSeeds relative to EBTI.

Conclusion

The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer.     

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis

Aims

Whether gemcitabine based chemoradiotherapy (GEM-based CRT) is superior to 5-fluorouracil based chemoradiotherapy (5-FU-based CRT) for locally advanced pancreatic cancer (LAPC) remains uncertain. The aim of the present study was to evaluate the effect of GEM-based CRT compared with 5-FU-based CRT.

Methods

Electronic database including Medline, Embase, Cochrane controlled trials register, PubMed (update to December 2010) and manual bibliography searches were carried out. A meta-analysis of all randomized clinical trials (RCTs) or other comparative studies comparing GEM-based CRT and 5-FU-based CRT were performed.

Results

Three RCTs and one retrospective comparative study including 229 patients were assessed. Meta-analysis showed survival advantage of GEM-based CRT compared with 5-FU-based CRT for 12-month (12-mo) survival rates (SRs) (RR = 1.54, 95% CI 1.05-2.26, p = 0.03). Moreover, there were also trends of benefit for SR after 6-months (RR 1.13, 95% CI 0.98-1.30, p = 0.09) and 24-months (24-mo: RR 2.41, 95% CI 0.90-6.48, p = 0.08), though the trends did not reach statistical significance. More frequent severe acute hematologic toxicities were found in the GEM-based CRT group.

Conclusions

The meta-analysis found that GEM-based CRT was better than 5-FU-based CRT in the treatment of LAPC, especially for 12-mo SRs. However, the acute toxicity should be carefully regarded.     

Urethral stricture following high dose rate brachytherapy for prostate cancer

Purpose

To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.

Methods and materials

Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results

At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008).

Conclusions

BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.     

Risk of coronary heart disease in patients with cancer: a nationwide follow-up study from Sweden

Background

Risk of coronary heart disease (CHD) in cancer patients has not been thoroughly investigated. The aim of the present study was to examine whether there is an association between cancer and first hospitalisation for CHD.

Methods

All individuals in Sweden with a diagnosis of cancer between 1st January 1987 and 31st December 2008 were followed for first hospitalisation for CHD. The reference population was the total population of Sweden without cancer. Standardised incidence ratios (SIRs) for CHD were calculated.

Results

The overall CHD risk during the first 6 months after diagnosis of cancer was 1.70 (95% confidence interval (95% CI) 1.66-1.75). For 26 of the 34 cancers studied, the risk of CHD was increased during the first 6 months after diagnosis of cancer. The overall CHD risk decreased rapidly, but remained slightly elevated, even 10+ years after diagnosis of cancer (SIR 1.07; 95% CI 1.04-1.11). The cancer sites/types for which risk of CHD was highest during the first 6 months were small intestine (SIR 2.88; 95% CI 2.02-3.99), leukaemia (SIR 2.84; 95% CI 2.37-3.37), kidney (SIR 2.65; 95% CI 2.30-3.04), lung (SIR 2.56; 95% CI 2.35-2.80) and liver (SIR 2.28; 95% CI 1.91-2.71). Metastases were associated with an increased risk of CHD (SIR 1.46; 95% CI 1.28-1.65).

Interpretation

Most cancers were associated with an increased risk of CHD during the first 6 months after diagnosis. CHD risk was related to the presence of metastates. Cancer patients may need a more aggressive treatment of classical CHD risk factors.     

Douglas peritonectomy compared to recto-sigmoid resection in optimally cytoreduced advanced ovarian cancer patients: analysis of morbidity and oncological outcome

Background

Rectosigmoidectomy (RR) with primary anastomosis or pelvic peritonectomy (PP) are often part of an optimal en bloc tumor resection in advanced ovarian cancer (AOC) patients with contiguous extension to or encasement of the reproductive organs, peritoneum of the cul-de-sac and sigmoid colon. We report our experience with two different surgical approaches in optimally cytoreduced AOC patients evaluating oncologic outcome and surgically associated morbidities

Methods

Data from all consecutive AOC patients undergoing PP or RR as part of the surgical procedure during primary cytoreduction from 2004 through 2009 were extrapolated and analyzed using the chi-squared test, Cox proportional hazard model and Kaplan-Meier method including log-rank test.

Results

During the study period, we identified 187 AOC patients, fitting the inclusion criteria: 71 (38%) were submitted to RR and 116 (62%) were managed with PP. The estimated mean disease-free survival (DFS) was 30.7 months (95% CI 24.6-36.8) in the RR arm vs. 25.9 months in the PP arm (95% CI 21.9-29.9) (p 0.299); similarly, the estimated mean overall survival (OS) was 38.8 months (95% CI 33.4-44.2) in the RR arm and 48.2 months in the PP arm (95% CI 43.1-53.3) (p = 0.122). No statistically significant differences were found in terms of DFS and OS according to the mesocolic lymphnode status (p = 0.65 and p = 0.81, respectively).

Conclusions

In conclusion, the current study clearly supports evidence that survival rates are similar for patients who achieved optimal residual tumor (RT), independent to whether they had RR or PP.     

Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection

Background

Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy.

Methods

One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009.

Results

The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval [CI], 5-15%), 44% (95% CI, 35-53%), and 2.0 months (95% CI, 1.4-2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4-16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12-43%); DCR, 72% (95% CI, 53-86%); and median PFS, 3.4 months (95% CI, 2.4-4.9 months).

Conclusions

Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies.     

The potential role of G2- but not of G0-radiosensitivity for predisposition of prostate cancer

Purpose

Comparing the chromosomal radiosensitivity of prostate cancer patients with that of healthy donors.

Materials and methods

The study was performed on 81 prostate cancer patients characterised by a clinical stage of predominantly pT2c or pT3a and a median age of 67 years. As healthy donors 60 male monozygotic twin pairs were recruited with a median age of 28 years. Chromosomal radiosensitivity was measured using both G0- and G2-assay.

Results

No difference between healthy donors and prostate cancer patients was detected concerning G0-radiosensitivity, since medians were similar (Hodges-Lehmann estimate: −0.05, 95% CI: −0.18-0.08, p = 0.4167). However, a pronounced difference was determined for G2-radiosensitivity with prostate cancer patients showing a significantly higher sensitivity compared to healthy donors (Hodges-Lehmann estimate: −0.41, 95% CI: −0.53 to −0.30, p = 1.75⁻⁹). Using the 90% quantile of G2-radiosensitivity in healthy donors as a threshold for discrimination the fraction of prostate cancer patients with elevated radiosensitivity increased to 49%.

Conclusion

G2-, but not G0-radiosensitivity is a promising marker for predisposition of prostate cancer.     

Radiotherapy for pituitary adenomas: Long-term efficacy and toxicity

Background

Radiotherapy for pituitary adenomas is an effective treatment but remains controversial due to toxicity concerns.

Materials and methods

A retrospective audit of patients referred for radiotherapy during 1974-2003 was conducted, the case records were examined and data linkage to cancer registry and hospital discharge records was performed to assess the overall survival (OS), progression-free survival (PFS) and late effects (hormone deficiency, reduced vision, second cancer and stroke).

Results

Three hundred and eighty-five patients had radiotherapy (median 45 Gy). The OS was 74% and 49%, PFS was 97% and 96%, at 10 and 20 years, respectively. No specific factors influenced local control. Additional hormone deficiencies occurred in 19% (ACTH) and 26% (TSH). Actuarial rate optic neuropathy at 10 years was 0.8%. Seventy-eight patients had a stroke, a RR for a matched Scottish population of 1.45 (CI 1.05-1.18, p = 0.03) men and 2.22 (1.56-3.08, p < 0.01) women. Four intra-cranial tumours were identified; 20-year actuarial risk 1.9% (CI 0-2.6%), a RR of 5.65 (0.53-20.77, p = 0.10) men and 9.94 (0.94-36.56, p = 0.04) women.

Conclusions

This treatment is effective with good local control rates at 20 years. A significant proportion developed hypo-pituitarism. The risk of optic neuropathy was low but risk of stroke increased, particularly in women who had slight increased risk of intra-cranial tumours.     

C-reactive protein-associated genetic variants and cancer risk: Findings from FINRISK 1992, FINRISK 1997 and Health 2000 studies

Background

Evidence from prospective observational studies suggests that elevated circulating C-reactive protein (CRP) concentrations are associated with cancer risk, but it is unclear whether this association is causal. In order to examine this, we investigated whether genetic variants that are associated with circulating CRP concentrations are associated with cancer risk.

Methods

We pooled data from three population-based prospective Finnish studies: FINRISK 1992 (n = 5289), FINRISK 1997 (n = 7160) and Health 2000 (n = 6299). Cancer cases were identified from cancer registrations. Thirteen CRP-associated SNPs, identified from genome-wide association studies, were genotyped. We examined the associations of the SNPs and cancer risk using Cox, probit and instrumented probit regression models.

Results

Compared to common allele homozygotes, individuals carrying one or two variant T alleles at rs1892534 had 1.05-fold (95% confidence interval (CI): 0.90, 1.23) and 1.2-fold (95% CI: 1.01, 1.42) increased overall cancer risk, respectively. Individuals with one or two variant A alleles at rs1169300 or rs2464196 had approximately 1.5- and 2-fold increased risk of lung cancer, respectively (p trend for both: 0.007). CRP SNPs were not associated with colorectal, prostate or breast cancer risk nor was CRP-associated with the probability of developing cancer in the instrumented probit analyses.

Conclusions

We found some evidence for an association of a small number of CRP-associated SNPs with the overall cancer risk and lung cancer risk. Our instrumental variable analyses provided no clear evidence for a causal association of CRP and cancer. These findings suggest that circulating CRP concentrations are unlikely to have a causal role in cancer.     

Increased cancer risks among arthroplasty patients: 30 year follow-up of the Swedish Knee Arthroplasty Register

Background

An increasing number of young patients are undergoing knee arthroplasties. Thus, the long-term risks of having a knee prosthesis must be evaluated. This study focuses on the potential carcinogenic effects of the prosthesis; it is a long-term follow-up of all patients in Sweden between 1975 and 2006.

Methods

The incidence of cancer in a total population of operated individuals was compared to the overall national cancer incidence in Sweden by means of standardised incidence ratios. Analysis of cancer latency period was performed to identify potential aetiological factors.

Results

For male and female patients with rheumatoid arthritis (RA) or osteoarthritis (OA), the overall cancer risks were elevated, ranging from 1.10 (95% confidence interval (CI): 1.03-1.18) for men with OA to 1.26 (1.23-1.29) for men with RA. The greatest increases in risk were observed for the leukaemia subtypes, myelodysplastic syndromes (MDS) and essential thrombocytosis (ET), ranging from 3.31 (1.24-8.83) for ET in men with OA to 7.38 (1.85-29.51) for ET in women with RA. Increases in risk were also observed for breast cancer, prostate cancer and melanoma. The latency analysis revealed elevated risks late in the study period for both solid and haematopoietic cancers. However, only increases in MDS and possibly prostate cancer and melanoma rates appeared to be connected to the operation.

Conclusion

This study showed that OA and RA arthroplasty patients have a significantly higher risk of cancer than the general population. Elevated risks of MDS and possibly prostate cancer and melanoma indicated a potential connection to exposure to metals in the implant. The observed excessive incidence of ET was likely associated with the inflammatory disease.     

Prostate cancer in the senior men from rural areas in east district of China: contemporary management and 5-year outcomes at multi-institutional collaboration

Objective

Prostate cancer is an underreported and emerging problem in China. Here we summarize the data for Chinese patients with prostate cancer (PCa), describe available treatment options, and report 5-year outcomes at multiple tertiary care institutions.

Patients and methods

A series of 1611 patients (mean age 76.51 years) diagnosed with PCa were enrolled. Survival rates for patients were analyzed using the Kaplan-Meier method. Prognostic factors for disease-specific survival were analyzed using the log-rank test and Cox proportional hazards model.

Results

Seven hundreds and thirty-two patients with a prostate tumor clinical stage of III or IV and 879 with a tumor clinical stage of I or II were diagnosed. The disease-specific survival rates at 1, 3 and 5 years were 94.6%, 81.3% and 72.6%, respectively. Five-year disease-specific survival rates were 99.2% for patients with low clinical stage PCa who underwent radical prostatectomy, 76.5% for those who underwent transurethral resection of the prostate plus hormone therapy, 38% for those who received hormone therapy plus radiation therapy and 29% for those that received hormone therapy alone.

Conclusions

In keeping with a lack of prostate-specific antigen (PSA)-based screening, Chinese men present later in life and course of their disease, with over 27% men dying of PCa at five years. Debulking of tumors by surgery and radiation therapy for high grade tumor may provide some survival benefit in the senior men but further study is required to validate these findings. It is important of the annual use of PSA test for men over 50 years old to detect the PCa in the early stage in this nation.     

False-positive screening results in the European randomized study of screening for prostate cancer

Background

Screening for prostate cancer (PC) with prostate-specific antigen (PSA) has been shown to decrease mortality, but has adverse effects, such as false-positive (FP) screening results. We describe the frequency of FP results and assess their relation to subsequent screening attendance, test results and prostate cancer risk in a large randomized trial.

Materials and methods

We included data from five centres of the European Randomized Study of Screening for Prostate Cancer, altogether over 61,000 screened men. Men were screened with PSA test at a 2-7 year interval depending on the centre; PSA cut-off was 3.0-4.0 ng/ml. A positive screen with no histologically confirmed PC in biopsy within 1 year was defined as an FP result.

Results

Of the 61,604 men who were screened at least once, 17.8% had one or more FP result(s). Almost 20% of men who participated at all screening rounds had one or more FP result(s). More than half of the men with an FP result had another FP if screened again. Men with FP results had a fourfold risk of PC at subsequent screen (depending on the round, 10.0% versus 2.6-2.7% of men with negative screen, risk ratio 3.8-3.9). The PCs following an FP result were in 92.8% of cases localised and low-grade versus 90.4% following a screen-negative result.

Conclusions

Our results show that FP results are common adverse effects in PC screening, as they affect at least one in six screened men. False-positive men are more prone to be diagnosed with PC but are also likely to have consistently high PSA levels.     

Risk for second primary non-breast cancer in pre- and postmenopausal women with breast cancer not treated with chemotherapy, radiotherapy or endocrine therapy

Introduction

We investigated the risk for a second primary cancer in pre- and postmenopausal women with breast cancer treated by surgery alone, to assess the importance of non-treatment factors and menopausal status.

Patients and methods

The cohort comprised 14,151 women with breast cancer diagnosed during 1977-2006, who did not receive radiotherapy or systemic adjuvant therapy. They were identified in the nationwide clinical database of the Danish Breast Cancer Cooperative Group. The women were followed for a second primary cancer other than breast cancer in the Danish Cancer Registry, and risk was quantified as standardised incidence ratios (SIRs).

Results

Women with breast cancer diagnosed before menopause had an 18% greater overall risk for a second primary non-breast cancer than the general female population (95% confidence interval [CI], 1.06-1.32). The excess was confined to cancers of the endometrium (1.5; 95% CI, 1.0-2.0) and ovaries (1.8; 95% CI, 1.2-2.4). Rare histological subtypes of breast cancer were associated with these two cancer sites. Women with breast cancer after menopause had no overall excess risk for a second cancer (SIR, 0.98; 95% CI, 0.92-1.04).

Conclusion

An excess risk for second non-breast cancers related to non-treatment factors is seen primarily in breast cancer patients who were premenopausal at diagnosis.     

Loose seeds versus stranded seeds in I-125 prostate brachytherapy: Differences in clinical outcome

Purpose

To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy.

Methods

From December 2000 until October 2006, we treated 896 T?2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n = 538) or loose seed (n = 358) I-125 implants. A total of 211 patients received a 6 months course of anti-androgen therapy, before treatment, for prostate volume reduction to <50 cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary.

Results

The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82-90) and 90% (85-95), the total 5-year bNED rate was 87% (85-90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34-0.97) for loose seeds versus stranded seeds.

Conclusions

These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants.     

Survival after radiotherapy in gastric cancer: Systematic review and meta-analysis

Background and purpose

A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer.

Methods

Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers’ score.

Results

Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT = 17) and 1.31 (95% CI: 1.04-1.66; NNT = 13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found.

Conclusion

This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.