The Association Between Modifiable Lifestyle Factors and Postoperative Complications of Elective Surgery in Patients With Colorectal Cancer.

BACKGROUND: Research has demonstrated a possible relation between patients' preoperative lifestyle and postoperative complications. OBJECTIVE: This study aimed to assess associations between modifiable preoperative lifestyle factors and postoperative complications in patients undergoing elective surgery for colorectal cancer. DESIGN: This is a retrospective study of a prospectively maintained database. SETTING: At diagnosis, data on smoking habits, alcohol consumption, BMI, and physical activity were collected by using questionnaires. Postoperative data were gathered from the nationwide database of the Dutch ColoRectal Audit. PATIENTS: Patients (n = 1564) with newly diagnosed stage I to IV colorectal cancer from 11 Dutch hospitals were included in a prospective observational cohort study (COLON) between 2010 and 2018. MAIN OUTCOME MEASURES: Multivariable logistic regression models were used to identify which preoperative lifestyle factors were associated with postoperative complications. RESULTS: Postoperative complications occurred in 28.5%, resulting in a substantially prolonged hospital stay (12 vs 5 days, p < 0.001). Independently associated with higher postoperative complication rates were ASA class II (OR, 1.46; 95% CI, 1.05-2.04; p = 0.03) and III to IV (OR, 3.17; 95% CI, 1.96-5.12; p < 0.001), current smoking (OR, 1.62; 95% CI, 1.02-2.56; p = 0.04), and rectal tumors (OR, 1.81; 95%CI, 1.28-2.55; p = 0.001). Body mass index, alcohol consumption, and physical activity did not show an association with postoperative complications. However, in a subgroup analysis of 200 patients with ASA III to IV, preoperative high physical activity was associated with fewer postoperative complications (OR, 0.17; 95% CI, 0.03-0.87; p = 0.04). LIMITATIONS: Compared with most studied colorectal cancer populations, this study describes a relatively healthy study population with 87.2% of the included patients classified as ASA I to II. CONCLUSIONS: Modifiable lifestyle factors such as current smoking and physical activity are associated with postoperative complications after colorectal cancer surgery. Current smoking is associated with an increased risk of postoperative complications in the overall study population, whereas preoperative high physical activity is only associated with a reduced risk of postoperative complications in patients with ASA III to IV. See Video Abstract at http://links.lww.com/DCR/B632. LA ASOCIACIN ENTRE FACTORES MODIFICABLES DEL ESTILO DE VIDA Y COMPLICACIONES POSOPERATORIAS EN CIRUGA ELECTIVA EN PACIENTES CON CNCER COLORECTAL: ANTECEDENTES:Estudios han demostrado una posible relación entre el estilo de vida preoperatorio de los pacientes y las complicaciones posoperatorias.OBJETIVO:Evaluar las asociaciones entre los factores de estilo de vida preoperatorios modificables y las complicaciones posoperatorias en pacientes llevados a cirugía electiva por cáncer colorrectal.DISEÑO:Estudio retrospectivo de una base de datos continua de forma prospectiva.ESCENARIO:En el momento del diagnóstico se recopilaron mediante cuestionarios datos sobre tabaquismo, consumo de alcohol, el IMC y la actividad física. Los datos posoperatorios se obtuvieron de la base de datos nacional de la Auditoría Colorectal Holandesa.PACIENTES:Se incluyeron pacientes (n = 1564) de once hospitales holandeses con cáncer colorrectal en estadio I-IV recién diagnosticado incluidos en un estudio de cohorte observacional prospectivo (COLON) entre 2010 y 2018.PRINCIPALES VARIABLES ANALIZADAS:Se utilizaron modelos de regresión logística multivariable para identificar qué factores de estilo de vida preoperatorios y se asociaron con complicaciones posoperatorias.RESULTADOS:Las complicaciones posoperatorias se presentaron en el 28,5%, lo que resultó en una estancia hospitalaria considerablemente mayor (12 contra 5 días, p <0,001). De manera independiente se asociaron con mayores tasas de complicaciones posoperatorias la clasificación ASA II (OR 1,46; 95% IC 1,05-2,04, p = 0,03) y III-IV (OR 3,17; 95% IC 1,96-5,12, p <0,001), tabaquismo presente (OR 1,62; IC 95% 1,02-2,56, p = 0,04) y tumores rectales (OR 1,81; IC 95% 1,28-2,55, p = 0,001). El IMC, el consumo de alcohol y la actividad física no mostraron asociación con complicaciones posoperatorias. Sin embargo, en un análisis de subgrupos de 200 pacientes ASA III-IV, la actividad física íntensa preoperatoria se asoció con menos complicaciones posoperatorias (OR 0,17; IC del 95%: 0,03-0,87, p = 0,04).LIMITACIONES:En comparación con las poblaciones de cáncer colorrectal más estudiadas, este estudio incluyó una población relativamente sana con el 87,2% de los pacientes incluidos clasificados como ASA I-II.CONCLUSIONES:Los factores modificables del estilo de vida, como son el encontrarse fumando y la actividad física, se asocian con complicaciones posoperatorias después de la cirugía de cáncer colorrectal. El encontrarse fumando se asocia con un mayor riesgo de complicaciones posoperatorias en la población general del estudio, mientras que la actividad física íntensa preoperatoria se asocia con un menor riesgo de complicaciones posoperatorias únicamente en pacientes ASA III-IV. Consulte Video Resumen en http://links.lww.com/DCR/B632.

An increase in physical activity after colorectal cancer surgery is associated with improved recovery of physical functioning: a prospective cohort study.

BACKGROUND: The influence of physical activity on patient-reported recovery of physical functioning after colorectal cancer (CRC) surgery is unknown. Therefore, we studied recovery of physical functioning after hospital discharge by (a) a relative increase in physical activity level and (b) absolute activity levels before and after surgery. METHODS: We included 327 incident CRC patients (stages I-III) from a prospective observational study. Patients completed questionnaires that assessed physical functioning and moderate-to-vigorous physical activity shortly after diagnosis and 6 months later. Cox regression models were used to calculate prevalence ratios (PRs) of no recovery of physical functioning. All PRs were adjusted for age, sex, physical functioning before surgery, stage of disease, ostomy and body mass index. RESULTS: At 6 months post-diagnosis 54% of CRC patients had not recovered to pre-operative physical functioning. Patients who increased their activity by at least 60 min/week were 43% more likely to recover physical function (adjusted PR 0.57 95%CI 0.39-0.82), compared with those with stable activity levels. Higher post-surgery levels of physical activity were also positively associated with recovery (P for trend = 0.01). In contrast, activity level before surgery was not associated with recovery (P for trend = 0.24). CONCLUSIONS: At 6 month post-diagnosis, about half of CRC patients had not recovered to preoperative functioning. An increase in moderate-to-vigorous physical activity after CRC surgery was associated with enhanced recovery of physical functioning. This benefit was seen regardless of physical activity level before surgery. These associations provide evidence to further explore connections between physical activity and recovery from CRC surgery after discharge from the hospital.

The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life.

BACKGROUND: There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the "COlorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life" - COLON - study. The main aim of this study is to assess associations of diet and other lifestyle factors, with colorectal cancer recurrence, survival and quality of life. We extensively investigate diet and lifestyle of colorectal cancer patients at diagnosis and during the following years; this design paper focusses on the initial exposures of interest: diet and dietary supplement use, body composition, nutrient status (e.g. vitamin D), and composition of the gut microbiota. METHODS/DESIGN: The COLON study is a multi-centre prospective cohort study among at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in the Netherlands. Patients with colorectal cancer are invited upon diagnosis. Upon recruitment, after 6 months, 2 years and 5 years, patients fill out food-frequency questionnaires; questionnaires about dietary supplement use, physical activity, weight, height, and quality of life; and donate blood samples. Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal muscle, subcutaneous fat, visceral fat and intermuscular fat, and to assess muscle attenuation. Blood samples are biobanked to facilitate future analyse of biomarkers, nutrients, DNA etc. Analysis of serum 25-hydroxy vitamin D levels, and analysis of metabolomic profiles are scheduled. A subgroup of patients with colon cancer is asked to provide faecal samples before and at several time points after colon resection to study changes in gut microbiota during treatment. For all patients, information on vital status is retrieved by linkage with national registries. Information on clinical characteristics is gathered from linkage with the Netherlands Cancer Registry and with hospital databases. Hazards ratios will be calculated for dietary and lifestyle factors at diagnosis in relation to recurrence and survival. Repeated measures analyses will be performed to assess changes over time in dietary and other factors in relation to recurrence and survival.

Body mass index is not a predictor of biochemical recurrence after radical prostatectomy in Dutch men diagnosed with prostate cancer.

PURPOSE: To determine the effect of body mass index (BMI) on clinical and pathological characteristics at time of diagnosis and on risk of biochemical recurrence after radical prostatectomy among Dutch men diagnosed with prostate cancer. METHODS: In total, 1,116 prostate cancer patients with known BMI, diagnosed between 2003 and 2006, were identified from the population-based cancer registry held by the Comprehensive Cancer Centre East, The Netherlands. Of these, 504 patients underwent a radical prostatectomy. Patients were categorized as normal weight (BMI < 25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI ≥ 30 kg/m(2)). Multivariable proportional hazards regression models, adjusted for age, prediagnostic PSA levels, and pathological characteristics were used to evaluate BMI as a prognostic factor for biochemical recurrence after radical prostatectomy. RESULTS: Overall, clinical and biopsy characteristics did not significantly differ among BMI groups. Pathological characteristics after radical prostatectomy did not significantly differ among BMI groups, except for tumor stage, which was highest in obese patients (P = 0.017). For patients treated with radical prostatectomy, 5-year risk (95% Confidence Intervals) of biochemical recurrence was 30% (23-37%) for normal weight, 32% (25-39%) for overweight, and 25% (9-41%) for obese patients (log rank P = 0.810). BMI was not an independent prognostic factor for biochemical recurrence in multivariable proportional hazards regression analyses (HR 0.99 per kg/m(2), 95% CI: 0.93-1.06). CONCLUSIONS: Compared with non-obese men, pathological tumor stage tended to be higher in obese men. Clinical relevance of this finding is unclear, because BMI was not an independent predictor of biochemical recurrence after radical prostatectomy.

Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas.

Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the "Metabolomic profiles throughout the continuum of colorectal cancer" (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the "Colorectal Cancer Study of Austria" (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.

Body mass index as a prognostic marker for biochemical recurrence in Dutch men treated with radical prostatectomy.

OBJECTIVE: To investigate whether body mass index (BMI) is a prognostic factor for biochemical recurrence (BCR) in Dutch men after radical prostatectomy (RP), as although epidemiological studies of obesity in relation to prostate cancer have provided conflicting results, recent studies from the USA suggest that a higher BMI is a risk factor for progression of prostate cancer. PATIENTS AND METHODS: Of the 1417 patients with prostate cancer who had RP at two University hospitals, 1302 were included in the present study. BMI (kg/m(2)) classes were defined as normal (<25), overweight (25-30) and obese (> or =30). The median follow-up was 59 months and clinical data were obtained retrospectively from charts. BCR was defined as two consecutive prostate-specific antigen (PSA) levels of >0.1 ng/mL. RESULTS: In all, 600 patients were classified as having normal weight (43.9%), 665 as overweight (48.6%) and 103 as obese (7.5%). Overall, 297 patients developed BCR after RP; the 10-year risk (95% confidence interval) of BCR was 31.9 (26.6-37.2)%, 30.5 (25.8-35.2)% and 23.9 (14.9-32.9)% for patients in the three categories, respectively (P = 0.836). Multivariable proportional hazard regression analyses of BMI and established prognostic factors for BCR did not change these results. CONCLUSION: BMI appeared to have no prognostic value for BCR in Dutch patients with clinically localized prostate cancer and treated with RP.

The prognostic role of the pathological T2 subclassification for prostate cancer in the 2002 Tumour-Nodes-Metastasis staging system.

OBJECTIVE: To evaluate the prognostic role of the 2002 Tumour-Nodes-Metastasis (TNM) pT2 subclassification for biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: The 1997 TNM staging system is based on one subdivision for organ-confined prostate tumours (T2a, unilateral; T2b, bilateral involvement). The 2002 TNM staging system subdivides unilateral involvement into T2a (half of one lobe or less) and T2b (more than one half of one lobe), while bilateral involvement is classified as T2c. In all, 542 patients were treated with RP at our institute; the RP specimens were completely embedded and histopathologically evaluated for Gleason grade, tumour volume and anatomical extent, and were staged according to the 2002 TNM staging criteria. Patients were followed for a median of 39.5 months. BCR was defined as two subsequent increasing prostate-specific antigen (PSA) levels of >0.10 ng/mL. Kaplan-Meier and proportional hazards regression analyses were used to evaluate the univariable and multivariable prognostic effect of tumour stage. RESULTS: According to the 2002 TNM staging system, 360 specimens were found to have pT2 tumours; 79 (22%) of the RP specimens were staged as pT2a and 281 (78%) as pT2c; no pT2b specimens were identified. Patients with unilateral involvement (pT2a) had a 5-year risk of BCR of 13%, while those with bilateral involvement (pT2c) had a risk of 23% (log rank test, P = 0.056). Patients with pT2c disease were more likely to have a larger tumour volume (Mann-Whitney U-test P < 0.001) and positive surgical margins (Fishers' exact test, P = 0.001)than those with pT2a tumours. Mann-Whitney U-tests showed no differences between the groups for preoperative PSA levels (P = 0.167). Also, the RP Gleason score was no different between groups (Pearson chi-square, P = 0.807). In the multivariable analyses, positive surgical margins appeared to increase the risk of BCR (hazard ratio 4.4, 95% confidence interval 2.5-7.9); pT2c vs pT2a had only a marginally (insignificant) additional effect (1.3, 0.6-2.7). CONCLUSION: The absence of a true unilateral pathological T2b tumour in a series of 360 pT2 RP specimens questions the relevance of substaging unilateral disease. The limited differences in BCR and in pathological features of unilateral vs bilateral pT2 prostate cancer justify modifying the TNM staging system to one with no subclassification of pT2 disease, or at most as only one subdivision into unilateral (T2a) and bilateral (T2b) disease, combining the T2b and T2c substages.

Dietary Intake of Magnesium or Calcium and Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer Patients.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe side-effect in colorectal cancer (CRC) patients. This study assessed the association between habitual dietary intake of magnesium or calcium and prevalence and severity of chronic CIPN in CRC patients receiving adjuvant chemotherapy. For this prospective cohort study, 196 CRC patients were considered. Magnesium and calcium intake was determined using a food frequency questionnaire at diagnosis, during and after chemotherapy. Chronic CIPN was assessed 12 months after diagnosis using the quality of life questionnaire CIPN20. Prevalence ratios were calculated to assess the association between magnesium or calcium intake and the prevalence of CIPN. Multivariable linear regression analysis was used to assess the association between magnesium or calcium intake and severity of CIPN. CIPN was reported by 160 (82%) patients. Magnesium intake during chemotherapy was statistically significantly associated with lower prevalence of CIPN (prevalence ratio (PR) 0.53, 95% confidence interval (CI) 0.32, 0.92). Furthermore, higher dietary intake of magnesium during (ß -1.08, 95% CI -1.95, -0.22) and after chemotherapy (ß -0.93, 95% CI -1.81, -0.06) was associated with less severe CIPN. No associations were found for calcium intake and the prevalence and severity of CIPN. To conclude, we observed an association between higher dietary magnesium intake and lower prevalence and severity of CIPN in CRC patients.

Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice.

The aging process is associated with diminished colonic health. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice.

Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin-6 and lower levels of various metabolites, among which are bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 µg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.

The effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjects.

BACKGROUND: Folate and its synthetic form folic acid function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF) study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of 2 years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n = 44 folic acid/vitamin B12, n = 43 placebo) using the Infinium HumanMethylation450 BeadChip. RESULTS: After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8, and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425, and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. CONCLUSIONS: Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.

Comparison of methods to assess body fat in non-obese six to seven-year-old children.

BACKGROUND & AIM: Different non-invasive methods exist to evaluate total body fat in children. Most methods have shown to be able to confirm a high fat percentage in children with overweight and obesity. No data are available on the estimation of total body fat in non-obese children. The aim of this study is to compare total body fat, assessed by different methods in non-obese children. METHODS: We compared total body fat, assessed by isotope dilution, dual energy X-ray, skinfold thickness, bioelectrical impedance analysis, combination of these methods as well as BMI in 30 six to seven-year-old children. RESULTS: The children had a mean BMI of 16.01kg/m(2) (range 13.51-20.32) and five children were overweight according to international criteria. Different methods showed rather different absolute values for total body fat. Bland-Altman analysis showed that the difference between the DEXA method and isotope dilution was dependent on the fat percentage. Children with the same BMI show a marked variation in total body fat ranging from 8% to 22% as estimated from the isotope dilution method. CONCLUSION: Non-invasive methods are presently not suited to assess the absolute amount of total body fat in 6-7 years old children.

A single institution experience with biochemical recurrence after radical prostatectomy for tumors that on pathology are of small volume or "insignificant".

OBJECTIVE: Small volume prostate cancers (<0.5 cc, svPC), and insignificant prostate cancers (<0.5 cc and Gleason scores <7, InsigPC) are considered clinically insignificant by some investigators. The aim of this study is to determine the biochemical recurrence rate (BCR) of svPC and InsigPC in prostatectomy specimens. METHODS: In total, 502 patients with prostate cancer, treated with radical prostatectomy (RP) between 1992 and 2005 and with detailed pathological classification, were included in the present study. Patients were postoperatively followed for a median period of 39.5 months (0.6-150). A total of 82 specimens (16.3%) with svPC including 64 (12.8%) with InsigPC were identified. BCR was defined as 2 consecutive PSA levels >0.10 ng/ml. RESULTS: In the total group, the median age at the time of surgery was 62.7 years (42.4-73.4) and the median preoperative PSA level was 8.0 ng/ml. Patients with InsigPC had Gleason scores of 4 in 7%, 5 in 37%, and 6 in 56%. Positive surgical margins were identified in 13 (15.9%) svPC and in 8 (12.7%) InsigPC specimens. The 5-year risk of BCR for the svPC group and the insigPC group was 10% (95% CI 2-18%, 7 and 5 patients, respectively) vs. 35% (95% CI 29-41%) in the rest of the cohort (log rank P = 0.001). CONCLUSION: Patients with svPC and patients with InsigPC have a significantly lower risk of BCR. However, even in this seemingly very favorable patient group, 1 in 10 patients will develop a BCR after RP. Therefore, new studies are needed to examine what the prognostic relevance is of small-volume tumors.