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 appro...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.展开更多
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 postoperati...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.展开更多
文摘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.
文摘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.
