Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model

BACKGROUND Cancer patients often suffer from severe stress reactions psychologically,such as anxiety and depression.Prostate cancer(PC)is one of the common cancer types,with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis.Therefore,attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment.AIM To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model.METHODS A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022.The patient cohort was divided into a training group(n=84)and a validation group(n=36)at a ratio of 7:3.The patients’anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale(SAS)and the Selfrating Depression Scale(SDS),respectively.Logistic regression was used to analyze the risk factors affecting negative mood,and a risk prediction model was constructed.RESULTS In the training group,35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50,respectively.Based on the scores,we further subclassified patients into two groups:a bad mood group(n=35)and an emotional stability group(n=49).Multivariate logistic regression analysis showed that marital status,castration scheme,and postoperative Visual Analogue Scale(VAS)score were independent risk factors affecting a patient's bad mood(P<0.05).In the training and validation groups,patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients(P<0.0001).The area under the curve(AUC)of the risk prediction model for predicting bad mood in the training group was 0.743,the specificity was 70.96%,and the sensitivity was 66.03%,while in the validation group,the AUC,specificity,and sensitivity were 0.755,66.67%,and 76.19%,respectively.The Hosmer-Lemeshow test showed aχ^(2) of 4.2856,a P value of 0.830,and a C-index of 0.773(0.692-0.854).The calibration curve revealed that the predicted curve was basically consistent with the actual curve,and the calibration curve showed that the prediction model had good discrimination and accuracy.Decision curve analysis showed that the model had a high net profit.CONCLUSION In PC patients,marital status,castration scheme,and postoperative pain(VAS)score are important factors affecting postoperative anxiety and depression.The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

Diabetes mellitus and prostate cancer risk:A mendelian randomization analysis

BACKGROUND Some studies have directed towards an association between diabetes mellitus(DM)and prostate cancer(PCa);however,this specific relationship remains inconclusive.In recent years,Mendelian randomization(MR)has become a widely used analytical method for inferring epidemiological causes.AIM To investigated the potential relationship between DM and PCa using MR.METHODS We downloaded relevant data on"diabetes"and"PCa"from the IEU OpenGWAS project database,performed three different methods to conduct MR,and carried out sensitivity analysis for verification.RESULTS The results indicated that DM was an independent risk factor for PCa.The odds ratio(OR)values obtained using the inverse variance weighted method in this study were as follows:OR=1.018(95%confidence interval:1.004-1.032),P=0.014.CONCLUSION We found that DM could increase the incidence rate of PCa.

Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on prostate cancer risk： an exploratory genotype-environment interaction study

Aim： To assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking. Methods： In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk. Results： The joint risk for smokers carrying Pro^＊ and MI^＊, Pro^＊ and GSTM1null or GSTM1 null and CYP1A1 MI^＊ variants was significantly higher （odds ratio [OR]： 13.13, 95% confidence interval [CI]： 2.41-71.36; OR： 3.97, 95% CI： 1.13-13.95 and OR： 6.87, 95% CI： 1.68-27.97, respectively） compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group （OR： 8.87, 95% CI： 1.25-62.71）. Conclusion： Our results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

Prostate cancer risk and aggressiveness associated with the CYPIB1 4326C/G （Leu432Val） polymorphism： a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B 1 （CYPIB1） 4326C/G variants and prostate cancer （PCa） risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYPIB1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians （OR= 1.52, 95% Ch 1.20-1.92）, and significant associations were also observed in a heterozygote comparison （OR= 1.40, 95% Ch 1.03-1.89）, a homozygote comparison （0R=2.38, 95% Ch 1.31-4.33） and in a dominant genetic model （OR = 1.52, 95% Ch 1.14-2.01）. Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa （OR= 1.13, 95% Ch 1.04-1.24）, and significant associations were observed in a heterozygote comparison （OR= 1.16, 95% Ch 1.02-1.33）, a homozygote comparison （OR= 1.24, 95% Ch 1.03-1.49） and a dominant genetic model （OR= 1.19, 95% Ch 1.05- 1.34）. The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYPIB1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.

The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism： a meta-analysis

To determine the risk, malignant degree and clinical progression of prostate cancer （PCa） associated with mouse double-minute 2 protein （MDM2） T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk （0R=0.85, 95% CI： 0.74-0.97）; this was also the case for the homozygous comparison （0R--0.72, 95% Ch 0.55-0.95） and the dominant genetic model （0R=0.79, 95% Ch 0.65-0.96）. The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy （0R=0.85, 95% Ch 0.75-0.96） in the overall analysis, as well as in the heterozygous comparison （0R=0.79, 95% Ch 0.65-0.96）, homozygous comparison （0R=0.76, 95% Ch 0.58-0.98） and dominant genetic model （0R=0.81, 95% CI： 0.68-0.96）. Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk （0R=0.77, 95% Ch 0.61-0.96）; this was also the case in the homozygous comparison （0R=0.51, 95% Ch 0.31-0.86）. The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

Identification of new genetic risk factors for prostate cancer

There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.

Contemporary approach to active surveillance for favorable risk prostate cancer

The approach to favorable risk prostate cancer known as“active surveillance”was first described explicitly in 2002.This was a report of 250 patients managed with a strategy of expectant management,with serial prostate-specific antigen and periodic biopsy,and radical intervention advised for patients who were re-classified as higher risk.This was initiated as a prospective clinical trial,complete with informed consent,beginning in 2007.Thus,there are now 20 years of experience with this approach,which has become widely adopted around the world.In this chapter,we will summarize the biological basis for active surveillance,review the experience to date of the Toronto and Hopkins groups which have reported 15-year outcomes,describe the current approach to active surveillance in patients with Gleason score 3þ3 or selected patients with Gleason score 3þ4 with a low percentage of Gleason pattern 4 who may also be candidates,enhanced by the use of magnetic resonance imaging,and forecast future directions.

Arg462Gln and Asp541Glu polymorphisms in ribonuclease L and prostate cancer risk:a meta-analysis

Objective：The association between ribonuclease L（RNASEL）gene polymorphisms and prostate cancer risk has been widely reported,but the results of these studies remained controversial and underpowered.We performed a meta-analysis of 28 studies to evaluate the association between Arg462Gln and Asp541Glu polymorphisms in the RNASEL gene and prostate cancer risk.Methods：Odds ratios（ORs）with 95%confidence intervals（CIs） were estimated to assess the association between RNASEL polymorphisms and prostate cancer risk.Results：A significantly increased prostate cancer risk was found for the Arg462Gln polymorphism in Africans（Gln/Gln vs Arg/Arg：OR=2.50,95%CI=1.28-4.87;Gln/Gln vs Gln/Arg＋Arg/Arg：OR=2.54,95%CI=1.30-4.95）,but not in Europeans and Asians.Additionally,the Asp541Glu polymorphism was associated with increased total prostate cancer risk（Glu-allele vs Asp-allele：OR=1.04,95%CI=1.01-1.07;Glu/Glu vs Asp/Asp：OR=1.22,95%CI= 1.03-1.46;Glu/Glu vs Glu/Asp＋Asp/Asp：OR=1.09,95%CI=1.02-1.16）.In the stratified analysis for the Asp541Glu polymorphism,there was a significantly increased prostate cancer risk in Africans and Europeans,and in hospital-based prostate cancer cases.Conclusion：The meta-analysis results showed evidence that RNASEL Arg462Gln and Asp541Glu polymorphisms are associated with prostate cancer risk and could be low-penetrance prostate cancer susceptibility biomarkers.

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

In European populations,7 single nucleotide polymorphisms(SNPs) on chromosome 17q,3 SNPs on 17q12,and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study.In Japanese populations,the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment.However,whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown.Therefore,we conducted a case-control study in a northern Chinese population and tested 2 SNPs,rs4430796 and rs1859962,on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve(PCR-HRM) combined with sequencing.We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles,onset ages,Gleason scores,PSA levels,and pathologic stages.We found a significant difference in the G allele of SNP rs1859962(P = 0.035,OR = 1.51,95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls(P > 0.05).Neither of the SNPs was significantly associated with the onset age,Gleason score,PSA level,pathologic stage,or other clinical indicators of patients with prostate cancer(P > 0.05).Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.

Association between p53 Pro72Arg polymorphism and prostate cancer risk:a meta-analysis

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios （RR） with 95% confidence intervals （CIs） were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found （Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, P heterogeneity = 0.016, I 2 = 55.8%; Pro/Pro＋Pro/Arg vs Arg/ Arg, RR = 1.05, 95%CI=1.00-1.11, P heterogeneity = 0.077, I 2 = 51.1%）. In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model （RR = 0.31, 95%CI=0.10- 0.91, P heterogeneity = 0.110, I 2 =60.8%）. This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.

Replication of Prostate Cancer Risk Variants in a Danish Case-Control Association Study

Background: Prostate cancer is one of the main causes for cancer morbidity and mortality in Western countries. Recently, several single nucleotide polymorphisms (SNPs) associated with prostate cancer have been identified in genome-wide association studies and multiple variant models have been developed to predict prostate cancer risk. The association between genetic markers and clinico-pathological tumor variables has, however, been inconsistent. Methods and Materials: A total of 32 previously identified prostate cancer-associated risk SNPs were genotyped in 648 prostate cancer cases and 526 age-matched controls. Family history was obtained by questionnaire. Age at diagnosis, clinical tumor variables including pre- and postoperative PSA, Gleason score, and T stage were obtained from prospectively collected clinical data (Aarhus Prostate Cancer Study). The SNPs were genotyped using Sequenom and Taqman assays and associations between SNPs, prostate cancer risk, and clinico-pathological variables were assessed. Results: Seventeen SNPs were successfully replicated in our case-control study and the association estimates were consistent with previous reports. Four markers were excluded from further analysis due to linkage disequilibrium. The cumulative effect of having the disease-associated genotype at five SNPs (rs4430796, rs6983267, rs1859962, rs1447295 and rs16901979) increased the prostate cancer risk with odds ratio 6.02 (95% CI: 2.21 - 16.38;P = 1.0 × 10–4) in patients with any combination of ≥4 markers compared with patients without any of the five SNPs (P for trend = 1.0 × 10–4). Six markers were significantly associated with clinico-pathological variables: SNP rs2735839 (GG) at locus 19q13, which is in the KLK3 gene encoding PSA, was associated with high preoperative PSA (P = 0.04), low Gleason score (P = 0.01) and low T stage (P = 0.02). Variants rs5759167 (GG/GT) (22q13) and rs7679673 (CC/CA) (4q24) were correlated with low risk for biochemical relapse (P = 0.015 and P = 0.009, respectively), whereas rs6983267 (GG) (8q24) was significantly associated with biochemical recurrence (P = 0.045). In addition, variants rs6983267 (GG) and rs5759167 (GG/GT) were significantly associated with negative family history (P = 0.04 and P = 0.02, respectively). Conclusion: We replicated 17 previously identified prostate cancer-associated risk SNPs in a Danish case-control study and found a cumulative and significant association between five SNPs and prostate cancer. Overall, we noted significant associations between several prostate cancer-associated risk genotypes and less aggressive tumor variables, high level of PSA, and low risk for biochemical reccurrence.

Influence of Dosimetric Considerations in Evaluating Second Cancer Risks in Prostate Cancer

Influence of dosimetric considerations in evaluating second cancer risks in prostate cancer. Material and methods: Fifteen patients in this study suffering from early stage of prostate cancer, each patient underwent three plans: 1) Three-dimensional conformal radiation therapy (3DCRT), 2) Rotation therapy (Arc therapy), and 3) intensity-modulated radiation therapy (IMRT) plan. Estimate secondary metastasis risk models: Excess Relative Risk (ERR) and Excess absolute risk (EAR) based on age of exposure by taking dosimetry data from Dose Volume Histograms (DVHs) to calculate risk models. Result: The second cancer risk models (ERR and EAR) for organs at risk OARs decrease with increasing age of exposure for 3D-CRT, ARC and IMRT and there is no significant difference for ERR and EAR model for developing second cancer risk in 3D-CRT, ARC and IMRT.

Locally advanced and high risk prostate cancer:The best indication for initial radical prostatectomy?

High risk prostate cancer is a deadly disease that needs aggressive treatment.High risk prostate cancer is often treated with androgen deprivation therapy or combined radiohormonotherapy while there is a place for surgery in cases of operable and resectable locally advanced or high risk disease.This review summarises the results of the different treatment strategies for locally advanced and high risk prostate cancer.Radical prostatectomy monotherapy or in combination with radiotherapy and/or hormonal treatment are analysed.They show that radical prostatectomy is an effective treatment modality for these tumours.After surgery,the results of the pathology and the follow-up of serum PSA may indicate the need of additional adjuvant or salvage treatment strategies.

High Grade Prostatic Intraepithelial Neoplasia and the Risk of Prostate Cancer

Introduction: High Grade Prostatic Intraepithelial Neoplasia (HGPIN) was originally thought to be a cancer precursor, but subsequent data has questioned its prognostic significance. We analyzed a large cohort of men diagnosed with HGPIN for subsequent occurrence of prostate cancer. Methods: From 2001 to 2011, we identified 567 men with isolated HGPIN and followed them for subsequent diagnosis of prostate cancer. Results: Two hundred and five patients were followed (median 5.9 years) without biopsy and remained clinically free of prostate cancer. The remaining 362 men underwent repeat biopsies and 133 (37%) were diagnosed with prostate cancer. The number of cores of HGPIN and whether they were unilateral or bilateral was not predictive for subsequent diagnosis of cancer. Prostate specific antigen was the only statistically significant predictor for prostate cancer. Conclusions: We found the incidence of cancer after a diagnosis of HGPIN to be 37%, which is consistent with other published series. This is only marginally higher than in patients re-biopsied after a prior benign biopsy. It appears that isolated HGPIN has only a small predictive value for subsequent diagnosis of prostate cancer. Therefore the finding of HGPIN should be used only in conjunction with other risk factors and patient considerations in deciding whether to proceed with further prostate biopsies.

Expending the Paradigm: Active Surveillance for Intermediate Risk Prostate Cancer

Prostate cancer is the leading male cancer worldwide. There remains a controversy as to which patients have indolent disease and which patients present an aggressive disease needing treatment with intent to cure. Because of quality of life impairment associated with treatment by radiation or surgery, active surveillance (AS) is a valid management option to avoid or differ aggressive treatment. Traditionally, AS was reserved for men with low risk prostate cancer, however intermediate risk patients are more and more found in AS cohorts. The aim of this review is to describe the place of AS in intermediate risk patients and the perspectives offered by such a treatment modality.

Combined cryotherapy and external beam radiation therapy for the treatment of intermediate-risk localized prostate cancer: A case series

Introduction: Routine PSA screening for prostate cancer (PCa) has increased the detection of intermediate-risk, localized disease. Conventional treatments for localized PCa include surgery, brachytherapy, cryotherapy or external beam radiotherapy (EBRT). However, for intermediate risk patients, rates of recurrence are moderately high and a multi-modal treatment approach for these patients may be necessary. We treated patients with a combination of cryotherapy and low dose EBRT to assess the safety and feasibility of this combinatory approach as well as to evaluate early oncological outcomes. Case Presentation: Men with intermediate risk (PSA = 10-20 ng/ml and/or Gleason = 7 and/or clinical T2b) localized PCa were prospectively enrolled in this study. Patients underwent cryotherapy and then 39 Gy EBRT 4-6 weeks after surgery. After completing EBRT, the men were followed every 3 months for 2 years. Adverse events, PSA, urinary and erectile function were assessed during each follow-up. Three patients completed the study. Preoperative PSA ranged from 3.5 to 7.9 ng/ml. There were no intraoperative complications and the treatment was well tolerated. Following cryotherapy and EBRT, all patients were pad-free within 6 months and remained continent for the duration of the study. Bother index remained stable throughout the study for all patients. No urethral strictures or rectal toxicities were observed. PSA remained undetectable for all patients. Conclusions: In this prospective study, cryotherapy combined with low dose EBRT was a safe approach for the treatment of intermediate-risk, localized PCa. Early oncological outcomes appeared to be favorable with all patients having undetectable PSA during the 2-year follow-up period. Further studies are warranted to confirm these preliminary results.

The Impact of Variation in Bladder Volume on the Doses of Target and Organ-at-Risk in Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%];the maximum dose to the small bowel [cGy];and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

Image-Guided Radiotherapy Dose Escalation in Intermediate and High Risk Cancer Prostate Patients and Its Effect on Treatment Toxicity

Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.

Pathologic and Prognostic Outcomes of Very Low- and Low-Risk Prostate Cancer According to the National Comprehensive Cancer Network Guidelines in Japanese Patients with Radical Prostatectomy

Background: The purpose of this study was to validate the treatment strategy for a cohort of Japanese patients with very low-risk (VLR) and low-risk (LR) prostate cancer according to the National Comprehensive Cancer Network (NCCN) guidelines. Methods: We studied 751 patients with T1- 3N0M0 prostate cancer treated with radical prostatectomy at our institution between 2000 and 2012. Patients with neoadjuvant treatments were excluded. We retrospectively reviewed the clinical and pathological outcomes for patients with VLR or LR prostate cancers that were classified by NCCN guidelines. Results: We identified 45 patients with VLR and 137 with LR prostate cancer. Non-biochemical recurrence rate at 5-year for 45 patients with VLR was 86.9% and 81.2% for 137 patients with LR (p = 0.56). However, none of the 19 patients >65 years old with VLR progressed, while 19% of 26 patients ≤65 years old with VLR cancer, 14% of patients >65 years old with LR cancer, and 17% of patients ≤65 years old with LR cancer progressed during the follow-up period (p = 0.04, p = 0.04 and p = 0.05, respectively). In analyses of prostatectomy specimens, both VLR and LR had similarly favorable outcomes, but patients >65 years old with VLR had the smallest tumors, with a mean of 5 mm in diameter. Conclusions: Our results support the treatment strategy of the NCCN that patients with VLR cancer and age >65 years old are good candidates for active surveillance, and that other treatment options—including active surveillance and aggressive treatments—can be applied to the remaining patients with VLR or LR cancers.