The active surveillance management approach for patients with low risk papillary thyroid microcarcinomas: is China ready?

Due to exponential increases in incidences,low risk papillary thyroid microcarcinoma(PTMC)has become a clinical and social issue in recent years.An active surveillance(AS)management approach is an alternative to immediate surgery for patients with low risk PTMC.With decreased doubts about the safety and validity due to evidence from a large number of studies,the AS approach has become increasingly popular worldwide.However,Chinese thyroid surgeons still lag behind other countries in their knowledge of clinical practices and research related to AS.To promote the implementation of AS in China,thyroid surgeons should understand the implications,advantages,and disadvantages of management approaches for AS,and should also consider the willingness of Chinese patients,the impact on the medical billing system,and the enthusiasm of doctors.Thus,a management approach for AS based on the Chinese population should be developed to reduce the risk of disease progression and enhance patient adherence.Herein,we summarize the recent research achievements and deficiencies in AS approaches,and describe the initial experiences regarding AS in the Chinese population,in order to assist Chinese thyroid surgeons in preparing for AS management in the era of PTMC precision medicine.

Active surveillance as a management strategy for papillary thyroid microcarcinoma

Active surveillance(AS)can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma(PTMC),with the absence of clinically apparent lymph nodes,extrathyroidal extensions,and distant metastasis.After reviewing the reports on AS of low risk PTMCs worldwide,we introduced AS,and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up schedules.Moreover,the requirement of cytological diagnosis,progression evaluation methods,necessity of thyrotropin suppression,and medical costs were issues that both clinicians and patients considered.The usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient risk.Clinicians may adopt measures like dynamic monitoring,risk stratification,and making personal follow-up schedules to minimize these potential risks.By appropriately selecting PTMC patients,AS can be an effective alternative treatment to immediate surgery.

PSA-based prostate cancer screening： the role of active surveillance and informed and shared decision making

Since the first publication describing the identification of prostate-specific antigen （PSA） in the 1960s, much progress has been made. The PSA test changed from being initially a monitoring tool to being also used as a diagnostic tool. Over time, the test has been heavily debated due to its lack of sensitivity and specificity. However, up to now the PSA test is still the only biomarker for the detection and monitoring of prostate cancer. PSA-based screening for prostate cancer is associated with a high proportion of unnecessary testing and overdiagnosis with subsequent overtreatment. In the early years of screening for prostate cancer, high rates of uptake were very important. However, over time the opinion on PSA-based screening has shifted towards the notion of informed choice. Nowadays, it is thought to be unethical to screen men without them being aware of the pros and cons of PSA testing, as well as the fact that an informed choice is related to better patient outcomes. Now, as the results of three major screening studies have been presented and the downsides of screening are becoming better understood, informed choice is becoming more relevant.

Active surveillance in low risk papillary thyroid carcinoma

In recent decades,while the incidence of thyroid cancer has increased exponentially around the world,mortality has remained stable.The vast majority of this increase is attributable to the identification of intrathyroidal papillary microcarcinomas,which exhibit slow growth rates with indolent courses.A diagnosis of thyroid cancer based upon the presence of these small tumors could be considered as an overdiagnosis,as the majority of these tumors would not likely result in death if left untreated.Although surgical resection was the classical standard therapy for papillary microcarcinomas,active surveillance(AS)has emerged over the last three decades as an alternative approach that is aimed to recognize a minority group of patients who will clinically progress and would likely benefit from rescue surgery.Despite the encouraging results of AS,its implementation in clinical practice is strongly influenced by psychosocial factors.The aim of this review is to describe the epidemiology,clinical evolution,prognostic factors,and mortality of papillary thyroid microcarcinomas.We also summarize the AS strategy according to published evidence,characterize the criteria for selecting patients for AS according to risk factors and environmental characteristics,as well as analyze the current limitations for AS implementation.

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.

Active surveillance as a practical strategy to differentiate lethal and non-lethal prostate cancer subtypes

Differentiation between lethal and non-lethal prostate cancer subtypes has become a very important issue in avoiding excessive treatment in an era when prostate-specific antigen （PSA） screening has reduced the rate of prostate cancer deaths by more than 20%. However, it is difficult to determine the patients who may or may not benefit from immediate treatment interventions at the time of the initial diagnosis. The selection of candidate patients who can postpone immediate treatment and undergo follow-ups with a specific surveillance program, or ＇active surveillance,＇ is a practical way to minimize overtreatment. In this review, the benefits and risks of active surveillance are discussed. Future perspectives, including imaging and new biomarkers for improving the outcomes of active surveillance programs, are also discussed.

Outcomes of combination MRI-targeted and transperineal template biopsy in restaging low-risk prostate cancer for active surveillance

Objective:Active surveillance(AS)offers a strategy to reduce overtreatment and now is a widely accepted treatment option for low-risk prostate cancer.An ideal tool for risk-stratification would detect aggressive cancers and exclude such men from taking up AS in the first place.We evaluate if a combination of transperineal template biopsy with magnetic resonance imaging(MRI)-targeted biopsy identifies significant prostate cancer amongst men initially diagnosed with low-risk prostate cancer.Methods:This prospective,single-blinded study included men with low-risk prostate cancer(D’Amico’s Criteria)diagnosed on conventional transrectal ultrasound-guided biopsy.Patients first underwent multiparametric MRI of the prostate
6 weeks after initial biopsy.Each suspicious lesion is mapped and assigned a Prostate Imaging Reporting and Data System(PIRADS)score.Template biopsy is first performed with the surgeon blinded to MRI findings followed by MRI-targeted biopsy using a robotic transperineal biopsy platform.Results:The age of the 19 men included is 65.4±4.9 years(mean±SD).Prostate specific antigen(PSA)at diagnosis and at the time of transperineal biopsy were comparable(7.3±1.7 ng/mL and 7.0±1.8 ng/mL,p Z 0.67),so were prostate volumes(34.2±8.9 mL and 32.1±13.4 mL,p Z 0.28).MRI-targeted biopsy had a higher percentage of cancer detection per core compared to template biopsy(11.7%vs.6.5%,p Z 0.02),this was more than 3 times superior for Gleason 7 disease(5.9%vs.1.6%,p<0.01).Four of 18(22.2%)patients with MRI lesions had significant disease with MRI-targeted biopsy alone.Three of 19 patients(15.8%)had significant disease with template biopsy alone.In combination,both techniques upclassified five patients(26.3%),all of whom underwent radical prostatectomy.Whole mount histology confirmed tumour location and grade.All six patients with PIRADS 5 lesions had cancer detected(66.6%significant disease).Conclusion:A combination of MRI-targeted and template biopsy may optimally risk-classify“low-risk”patients diagnosed on initial conventional transrectal ultrasonography(TRUS)prostate biopsy.

Active surveillance in metastatic pancreatic neuroendocrine tumors:A 20-year single-institutional experience

BACKGROUND Pancreatic neuroendocrine tumors(PanNETs)are heterogeneous and indolent;systemic therapy is not essential for every patient with metastatic PanNET.The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis,if the patient has stable disease.However,specific factors that influence surveillance were not mentioned.In addition,data regarding the period of active surveillance in patients with metastatic PanNET are lacking.AIM To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs(NF-PanNETs).METHODS Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled.Time to disease progression(TTP)and time to initiation of systemic therapy were determined.RESULTS Thirty-one(40.8%)patients had recurrent liver disease after R0 resection;45(59.2%)were diagnosed with liver metastasis.The median follow-up period was 42 mo and 90.7%patients were observed to have disease progression.The median TTP(mTTP)was 10 mo.Multivariate analysis showed that the largest axis of the liver metastasis>5 mm(P=0.04),non-resection of the primary tumor(P=0.024),and T3-4 stage(P=0.028)were associated with a shorter TTP.The mTTP in patients with no risk factors was 24 mo,which was significantly longer than that in patients with one(10 mo)or more(6 mo)risk factors(P<0.001).A nomogram with three risk factors showed reasonable calibration,with a C-index of 0.603(95%confidence interval:0.47-0.74).CONCLUSION Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors,and other patients progressed rapidly without treatment.Further studies with a larger sample size and a control group are needed.

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,China.We investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease progression.Moreover,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 lesions.The study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated biopsy.The combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

Treatment of intermediate-risk prostate cancer with active surveillance in the routine care—Long-term outcomes of a prospective noninterventional study(HAROW)

Background:We report here the long-term outcomes of patients with intermediate-risk prostate cancer(PCa)treated with active surveillance(AS)in a daily routine setting.Material andmethods:HAROW(2008–2013)was a noninterventional,health service research study investigating themanagement of localized PCa in a community setting.A substantial proportion of the study centers were office-based urologists.A follow-up examination of all intermediate-risk patients with AS was conducted.Overall,cancer-specific,metastasis-free,and treatment-free survival rates,as well as reasons for discontinuation,were determined and discussed.Results:Of the 2957 patients enrolled,52 with intermediate-risk PCa were managed with AS and were available for evaluation.The median follow-up was 6.8 years(interquartile range,3.4–8.6 years).Seven patients(13.5%)died of causes unrelated to PCa,of whom 4 were under AS or under watchful waiting.Two patients(3.8%)developed metastasis.The estimated 8-year overall,cancer-specific,metastasis-free,and treatment-free survival rates were 85%(95%confidence interval[CI],72%–96%),100%,93%(95%CI,82%–100%),and 31%(95%CI,17%–45%),respectively.Onmultivariable analysis,prostate-specific antigen density of≥0.2 ng/mL2 was significantly predictive of receiving invasive treatment(hazard ratio,3.29;p=0.006).Reasons for discontinuation were more often due to patient's or physician's concerns(36%)than due to observed clinical progression.Conclusions:Although survival outcome data for intermediate-risk patients managed with AS in real-life health care conditions were promising,rates of discontinuation were high,and discontinuation was often a patient's decision,even when the signs of disease progression were absent.This might be an indication of higher levels of mental burden and anxiety in this specific subgroup of patients,which should be considered when making treatment decisions.From a psychological perspective,not all intermediate-risk patients are optimal candidates for AS.

Can testosterone therapy be offered to men on active surveillance for prostate cancer？ Preliminary results

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance （AS） for Gleason 3 ＋ 3 and Gleason 3 ＋ 4 prostate cancer （PCa）. A retrospective chart review identified 28 men with T deficiency who underwent T therapy （T group） for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency （no-T group） was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 ＋ 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 （10.7%） men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 ＋ 3 disease, 7 （31.8%） men developed biopsy progression including 3 men （13.6%） who developed Gleason 3 ＋ 4 PCa. Of 6 men with Gleason 3 ＋ 4 disease at baseline, 2 （33.3%） men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 ＋ 4. All 96 men in the no-T group had Gleason 3 ＋ 3 disease at baseline and, 43 （44.7%） developed biopsy progression, including 9 men （9.38%） with upgrading to Gleason 7 （3 ＋ 4）. Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer:a real-world study from the SEER database

To reduce treatment-related side effects in low-risk prostate cancer(PCa),both focal therapy and deferred treatments,including active surveillance(AS)and watchful waiting(WW),are worth considering over radical prostatectomy(RP).Therefore,this study aimed to compare long-term survival outcomes between focal therapy and AS/WW.Data were obtained and analyzed from the Surveillance,Epidemiology,and End Results(SEER)database.Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included.Focal therapy included cryotherapy and laser ablation.Multivariate Cox proportional hazards models were used to compare overall mortality(OM)and cancer-specific mortality(CSM)between AS/WW and focal therapy,and propensity score matching(PSM)was performed to reduce the influence of bias and unmeasured confounders.A total of 19292 patients with low-risk PCa were included in this study.In multivariate Cox proportional hazards model analysis,the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW(hazard ratio[HR]=1.35,95%confidence interval[CI]:1.02–1.79,P=0.037),whereas no significant difference was found in CSM(HR=0.98,95%CI:0.23–4.11,P=0.977).After PSM,the OM and CSM of focal therapy and AS/WW showed no significant differences(HR=1.26,95%CI:0.92–1.74,P=0.149;and HR=1.26,95%CI:0.24–6.51,P=0.782,respectively).For patients with low-risk PCa,focal therapy was no match for AS/WW in decreasing OM,suggesting that AS/WW could bring more overall survival benefits.

The comparison of survival between active surveillance or watchful waiting and focal laser ablation in patients with low-risk prostate cancer

Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the choice between these options in clinical practice needs further study.Therefore,this study aims to compare and analyze their effects based on overall survival(OS)and cancer-specific survival(CSS)to obtain better long-term benefits.We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010–2016.Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups.To eliminate bias,this study applied a series of sensitivity analyses.Moreover,Kaplan–Meier curves were plotted to obtain survival status.A total of 18841 patients with low-risk PCa were included,with a median of 36-month follow-up.According to the multivariate Cox proportional hazard regression,the FLA group presented inferior survival benefits in OS than the AS/WW group(hazard ratio[HR]:2.13,95%confidence interval[CI]:1.37–3.33,P<0.05).After adjusting for confounders,the result persisted(HR:1.69,95%CI:1.02–2.81,P<0.05).According to the results of the sensitivity analysis,the inverse probability of the treatment weighing model indicated the same result in OS.In conclusion,AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment.Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa.More relevant researches and data will be needed for further clarity.

The current role of prostate multiparametric magnetic resonance imaging

Prostate multi-parametric magnetic resonance imaging(mpMRI)has shown excellent sensitivity for Gleason
7 cancers,especially when their volume is
0.5 mL.As a result,performing an mpMRI before prostate biopsy could improve the detection of clinically significant prostate cancer(csPCa)by adding targeted biopsies to systematic biopsies.Currently,there is a consensus that targeted biopsies improve the detection of csPCa in the repeat biopsy setting and at confirmatory biopsy in patients considering active surveillance.Several prospective multicentric controlled trials recently showed that targeted biopsy also improved csPCa detection in biopsy-naǐve patients.The role of mpMRI and targeted biopsy during the follow-up of active surveillance remains unclear.Whether systematic biopsy could be omitted in case of negative mpMRI is also a matter of controversy.mpMRI did show excellent negative predictive values(NPV)in the literature,however,since NPV depends on the prevalence of the disease,negative mpMRI findings should be interpreted in the light of a priori risk for csPCa of the patient.Nomograms combining mpMRI findings and classical risk predictors(age,prostatespecific antigen density,digital rectal examination,etc.)will probably be developed in the future to decide whether a prostate biopsy should be obtained.mpMRI has a good specificity for detecting T3 stage cancers,but its sensitivity is low.It should therefore not be used routinely for staging purposes in low-risk patients.Nomograms combining mpMRI findings and other clinical and biochemical data will also probably be used in the future to better assess the risk of T3 stage disease.

Nuclear morphometry, nucleomics and prostate cancer progression

Prostate cancer （PCa） results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults （such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks）, followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the ＇tumor microenvironment＇ in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a ＇seed and soil＇ site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin （DNA transcription） organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management.

Up to Date Management of DCIS and Future Directions

Ductal carcinoma in situ (DCIS) is a non-invasive malignancy confined within the basement membrane of the breast ductal system. There is a lot of disparity in the natural history of DCIS with an estimated incidence of progression to invasive ductal carcinoma between 20% to 53% over ten or more years after initial diagnosis. The surgical and adjuvant management of DCIS has advanced significantly in the last couple of decades. Nonetheless, surgeons, medical oncologists, and radiation oncologists, along with their patients, still depend on conventional clinical and pathologic risk factors to make management decisions. Irrespective of the management strategy, long-term survival is excellent. The debate around DCIS relates to preventing either under-treatment or over-treatment. In this paper, we will review the incidence and management options of DCIS. Additionally, we will focus on several current disputes related to the management of DCIS, including breast conserving surgery, the role of radiation in breast conservation surgery, sentinel node biopsy in DCIS, hormonal therapy, various risk stratification schemes, and the option of active surveillance for low-risk DCIS.

Molecular profiling of indolent human prostate cancer： tackling technical challenges to achieve high-fidelity genome-wide data

The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded （FFPE） tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.

Treatment of clinical stage I non-seminoma

Germ cell cancers are the most common solid tumors among men between 15 and 40 years.Non-seminomatous germ cell tumors(NSGCTs)represent a unique and exclusive cohort of germ cell tumor patients.Non-seminoma can harbor different histologic components.The most commonly found histologies are embryonal cell cancer,teratoma,yolk sack tumor and choriocarcinoma,as well as teratocarcinoma and seminoma,in combination with non-seminomatous germ cell tumors histologic types.The clinical definition of stage I nonseminoma is the absence of metastatic lesions on imaging and normal tumor markers.The cure rate for clinical stage I NSGCT is 99%and this can be achieved by three therapeutic strategies:Active surveillance with treatment at the time of relapse,retroperitoneal lymph node dissection or adjuvant chemotherapy.The balancing of these various strategies should always be based on an individual risk profile of NGSCG patient depending on the lymphovascular invasion of the tumor.

Oesophageal cancer metastases:An observational study of a more aggressive approach

BACKGROUND The prognosis for oesophageal carcinoma is poor,but once distant metastases emerge the prognosis is considered hopeless.There is no consistent protocol for the early identification and aggressive management of metastases.AIM To examine the outcome of a policy of active postoperative surveillance with aggressive treatment of confirmed metastases.METHODS A prospectively maintained database of 205 patients diagnosed with oesophageal carcinoma between 1998 and 2019 and treated with curative intent was interrogated for patients with metastases,either at diagnosis or on follow-up surveillance and treated for cure.This cohort was compared with incomplete clinical responders to neoadjuvant chemoradiotherapy(nCRT)who subsequently underwent surgery on their primary tumour.Overall survival was estimated using the Kaplan-Meier method,and the log-rank test was used to compare survival differences between groups.RESULTS Of 205 patients,11(5.4%)had metastases treated for cure(82%male;median age 60 years;9 adenocarcinoma and 2 squamous cell carcinomas).All had undergone neoadjuvant chemotherapy or chemoradiotherapy,followed by surgery in all but 1 case.Of the 11 patients,4 had metastatic disease at diagnosis,of whom 3 were successfully downstaged with nCRT before definitive surgery;2 of these 4 also developed oligometastatic recurrence and were treated with curative intent.Following definitive treatment,7 had treatment for metachronous oligometastatic disease;5 of whom underwent metastasectomy(adrenal×2;lung×2;liver×1).The median overall survival was 10.9 years[95%confidence interval(CI):0.7-21.0 years],which was statistically significantly longer than incomplete clinical responders undergoing surgery on the primary tumour without metastatic intervention[n=62;median overall survival=1.9(95%CI:1.1-2.7;P=0.012].The cumulative proportion surviving 1,3,and 5 years was 100%,91%,and 61%,respectively compared to 71%,36%,and 25%for incomplete clinical responders undergoing surgery on the primary tumour who did not undergo treatment for metastatic disease.CONCLUSION Metastatic oesophageal cancer represents a unique challenge,but aggressive treatment can be rewarded with impressive survival data.In view of recent advances in targeted therapies,intensive follow-up may yield a greater number of patients with curative potential and thus improved long-term survival.

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.