Management of lateral pelvic lymph nodes in rectal cancer:Is it time to reach an Agreement?

In this editorial,we proceed to comment on the article by Chua et al,addressing the management of metastatic lateral pelvic lymph nodes(mLLN)in stage II/III rectal cancer patients below the peritoneal reflection.The treatment of this nodal area sparks significant controversy due to the strategic differences followed by Eastern and Western physicians,albeit with a higher degree of convergence in recent years.The dissection of lateral pelvic lymph nodes without neoadjuvant therapy is a standard practice in Eastern countries.In contrast,in the West,preference leans towards opting for neoadjuvant therapy with chemoradiotherapy or radiotherapy,that would cover the treatment of this area without the need to add the dissection of these nodes to the total mesorectal excision.In the presence of high-risk nodal characteristics for mLLN related to radiological imaging and lack of response to neoadjuvant therapy,the risk of lateral local recurrence increases,suggesting the appropriate selection of strategies to reduce the risk of recurrence in each patient profile.Despite the heterogeneous and retrospective nature of studies addressing this area,an international consensus is necessary to approach this clinical scenario uniformly.

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.

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.

Metastatic hormone-sensitive prostate cancer:How should it be treated?

The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years.The classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered suboptimal.Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel,abiraterone acetate,enzalutamide,apalutamide,and/or radiotherapy to the primary tumour.As a result,these approaches are now included in treatment guidelines and considered standard of care.However,the different treatment strategies have not been directly compared,and thus treatment selection remains at the discretion of the individual physician or,ideally,a multidisciplinary team.Given the range of available treatment approaches with varying toxicity profiles,treatment selection should be individualized based on the patient’s clinical characteristics and preferences,which implies active patient participation in the decision-making process.In the present document,we discuss the changing landscape of the management of patients with metastatic hormonesensitive prostate cancer in the context of several recently-published landmark randomized trials.In addition,we discuss several unresolved issues,including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.

Assessing radiation dose for postoperative radiotherapy in prostate cancer: Real world data

BACKGROUND Approximately 30%of patients with localized prostate cancer(PCa)who undergo radical prostatectomy will develop biochemical recurrence.In these patients,the only potentially curative treatment is postoperative radiotherapy(PORT)with or without hormone therapy.However,the optimal radiotherapy dose is unknown due to the limited data available.AIM To determine whether the postoperative radiotherapy dose influences biochemical failure-free survival(BFFS)in patients with PCa.METHODS Retrospective analysis of patients who underwent radical prostatectomy for PCa followed by PORT-either adjuvant radiotherapy(ART)or salvage radiotherapy(SRT)-between April 2002 and July 2015.From 2002 to 2010,the prescribed radiation dose to the surgical bed was 66-70 Gy in fractions of 2 Gy;from 2010 until July 2015,the prescribed dose was 70-72 Gy.Patients were grouped into three categories according to the total dose administered:66-68 Gy,70 Gy,and 72 Gy.The primary endpoint was BFFS,defined as the post-radiotherapy prostatespecific antigen(PSA)nadir+0.2 ng/mL.Secondary endpoints were overall survival(OS),cancer-specific survival(CSS),and metastasis-free survival(MFS;based on conventional imaging tests).Treatment-related genitourinary(GU)and gastrointestinal(GI)toxicity was evaluated according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.Finally,we aimed to identify potential prognostic factors.BFFS,OS,CSS,and MFS were calculated with the Kaplan-Meier method and the log-rank test.Univariate and multivariate Cox regression models were performed to explore between-group differences in survival outcome measures.RESULTS A total of 301 consecutive patients were included.Of these,93(33.6%)received ART and 186(66.4%)SRT;22 patients were excluded due to residual macroscopic disease or local recurrence in the surgical bed.In this subgroup(n=93),43 patients(46.2%)were Gleason score(GS)≤6,44(47.3%)GS 7,and 6(6.5%)GS≥8;clinical stage was cT1 in 51(54.8%),cT2 in 35(39.3%),and cT3 in one patient(1.1%);PSA was<10 ng/mL in 58(63%)patients,10-20 ng/mL in 28(30.6%),and≥20 ng/mL in 6(6.4%)patients.No differences were found in BFFS in this patient subset versus the entire cohort of patients(P=0.66).At a median follow-up of 113 months(range,4-233),5-and 10-year BFFS rates were 78.8%and 73.7%,respectively,with OS rates of 93.3%and 81.4%.The 5-year BFFS rates in three groups were as follows:69.6%(66-68 Gy),80.5%(70 Gy)and 82.6%(72 Gy)(P=0.12):the corresponding 10-year rates were 63.9%,72.9%,and 82.6%(P=0.12),respectively.No significant between-group differences were observed in MFS,CSS,or OS.On the univariate analysis,the following variables were significantly associated with BFFS:PSA at diagnosis;clinical stage(cT1 vs cT2);GS at diagnosis;treatment indication(ART vs SRT);pre-RT PSA levels;and RT dose 66-68 Gy vs.72 Gy(HR:2.05;95%CI:1.02-4.02,P=0.04).On the multivariate analysis,the following variables remained significant:biopsy GS(HR:2.85;95%CI:1.83-4.43,P<0.001);clinical stage(HR:2.31;95%CI:1.47-4.43,P=0.01);and treatment indication(HR:4.11;95%CI:2.06-8.17,P<0.001).Acute grade(G)1 GU toxicity was observed in 11(20.4%),17(19.8%),and 3(8.3%)patients in each group(66-68 Gy,70 Gy and 72 Gy),respectively(P=0.295).Acute G2 toxicity was observed in 2(3.7%),4(4.7%)and 2(5.6%)patients,respectively(P=0.949).Acute G1 GI toxicity was observed in 16(29.6%),23(26.7%)and 2(5.6%)patients in each group,respectively(P=0.011).Acute G2 GI toxicity was observed in 2(3.7%),6(6.9%)and 1(2.8%)patients,respectively(P=0.278).No cases of acute G3 GI toxicity were observed.CONCLUSION The findings of this retrospective study suggest that postoperative radiotherapy dose intensification in PCa is not superior to conventional radiotherapy treatment.