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.

Survival in men older than 75 years with low- and intermediate-grade prostate cancer managed with watchful waiting with active surveillance

Objective:Recent studies have reported the underuse of active surveillance or watchful wait-ing for low-risk prostate cancer in the United States.This study examined prostate cancer-specific and all-cause death in elderly patients older than 75 years with low-risk tumors managed with active treatment versus watchful waiting with active surveillance(WWAS).Methods:We performed survival analysis in a cohort of 18,599 men with low-risk tumors(early and localized tumors)who were 75 years or older at the time of prostate cancer diagnosis in the linked Surveillance,Epidemiology,and End Results(SEER)-Medicare database(from 1992 to 1998)and who were followed up through December 2003.WWAS was defined as having an-nual screening for prostate-specific antigen and/or digital rectal examination during the follow-up period.The risks of prostate cancer-specific and all-cause death were compared by Cox regression models.The propensity score matching technique was used to address potential selection bias.Results:In patients with well-differentiated(Gleason score 2-4)and localized disease,those managed with WWAS without delayed treatment had higher risk of all-cause death(hazard ratio 1.20,95%confidence interval 1.13-1.28)but a substantially lower risk of prostate cancer-specific death(hazard ratio 0.62,confidence interval 0.51-0.75)than patients undergoing active treatment.Patients managed with WWAS with delayed treatment had comparable mortality outcomes.Sensi-tivity analyses based on propensity score matching yielded similar results.Conclusion:In men older than 75 years with well-differentiated and localized prostate cancer,WWAS without delayed treatment had a lower risk of prostate cancer-specific death and compa-rable all-cause death as compared with active treatment.Those patients in whom treatment was delayed had comparable mortality outcomes.Our results support WWAS as an initial management option for older men with well-differentiated and localized prostate cancer.

Neoadjuvant treatment of rectal cancer: Where we are and where we are going

Locally advanced rectal cancer requires a multidisciplinary approach based on total neoadjuvant treatment with radiotherapy(RT)and chemotherapy(ChT),followed by deferred surgery.Currently,alternatives to the standard total neoadjuvant therapy(TNT)are being explored,such as new ChT regimens or the introduction of immunotherapy.With standard TNT,up to a third of patients may achieve a complete pathological response(CPR),potentially avoiding surgery.However,as of now,we lack predictive markers of response that would allow us to define criteria for a conservative organ strategy.The presence of muta-tions,genes,or new imaging tests is helping to define these criteria.An example of this is the diffusion coefficient in the diffusion-weighted sequence of magnetic resonance imaging and the integration of this imaging technique into RT treatment.This allows for the monitoring of the evolution of this coefficient over successive RT sessions,helping to determine which patients will achieve CPR or those who may require intensification of neoadjuvant therapy.

Recent advances in the management of rectal cancer: No surgery, minimal surgery or minimally invasive surgery

Over the last decade,with the acceptance of the need for improvements in the outcome of patients affected with rectal cancer,there has been a significant increase in the literature regarding treatment options available to patients affected by this disease.That treatment related decisions should be made at a high volume multidisciplinary tumor board,after pre-operative rectal magnetic resonance imaging and the importance of total mesorectal excision(TME)are accepted standard of care.More controversial is the emerging role for watchful waiting rather than radical surgery in complete pathologic responders,which may be appropriate in 20%of patients.Patients with early T1 rectal cancers and favorable pathologic features can be cured with local excision only,with transanal minimal invasive surgery(TAMIS)because of its versatility and almost universal availability of the necessary equipment and skillset in the average laparoscopic surgeon,emerging as the leading option.Recent trials have raised concerns about the oncologic outcomes of the standard"top-down"TME hence transanal TME(Ta TME"bottom-up")approach has gained popularity as an alternative.The challenges are many,with a dearth of evidence of the oncologic superiority in the long-term for any given option.However,this review highlights recent advances in the role of chemoradiation only for complete pathologic responders,TAMIS for highly selected early rectal cancer patients and Ta TME as options to improve cure rates whilst maintaining quality of life in these patients,while we await the results of further definitive trials being currently conducted.

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.

Watch and wait approach in rectal cancer:Current controversies and future directions

According to the main international clinical guidelines,the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery.However,doubts have been raised about the appropriate definition of clinical complete response(cCR)after neoadjuvant therapy and the role of surgery in patients who achieve a cCR.Surgical resection is associated with significant morbidity and decreased quality of life(QoL),which is especially relevant given the favourable prognosis in this patient subset. Accordingly, therehas been a growing interest in alternative approaches with less morbidity,including the organ-preserving watch and wait strategy, in which surgery isomitted in patients who have achieved a cCR. These patients are managed with aspecific follow-up protocol to ensure adequate cancer control, including the earlyidentification of recurrent disease. However, there are several open questionsabout this strategy, including patient selection, the clinical and radiologicalcriteria to accurately determine cCR, the duration of neoadjuvant treatment, therole of dose intensification (chemotherapy and/or radiotherapy), optimal followupprotocols, and the future perspectives of this approach. In the present review,we summarize the available evidence on the watch and wait strategy in thisclinical scenario, including ongoing clinical trials, QoL in these patients, and thecontroversies surrounding this treatment approach.

Watch and wait in locally advance rectal cancer:Past,present and future

In rectal cancer,a complete pathological response after neoadjuvant therapy means better rates survival and better rates of local recurrence.Nevertheless,these patients suffer from complications following surgery such as low anterior resection syndrome,sexual dysfunction or colostomy for the rest of their lives.Due to this,several groups are working in an organ preservation strategy when a clinical response is diagnosed.This strategy is known as watch and wait.In this editorial,we review the past,present and future perspectives for this conservative management.

“Watch and wait”strategy after neoadjuvant chemoradiotherapy in rectal cancer:opportunities and challenges

The"watch and wait"(W&W)strategy has been widely used in rectal cancer patients who have achieved clinical complete response(cCR)after neoadjuvant chemoradiotherapy(nCRT),which can save them from surgery and improve their quality of life.However,this strategy also has many unsolved practical problems,including the improvement of cCR/pCR rate,the search for efficient predictors,the standard follow-up and the methods of rescue surgery,etc.Larger sample size and more standardized clinical trials are still needed to obtain credible evidence.Therefore,we must rationally view the cCR after nCRT for middle and low rectal cancer,understand the risk of W&W strategy,and make a reasonable choice.It is particularly important to emphasize that we should actively carry out prospective multi-center clinical trials to produce high-level evidence suitable for Chinese characteristics,so that more rectal cancer patients can benefit from nCRT.