TY - JOUR
AU - Kageyama, Yukio
AB - Abstract Objective To investigate the incidence of colorectal cancer and chronic radiation proctitis after prostate radiotherapy using periodic total colonoscopy screening. Methods From February 2013 to January 2018, 270 patients who underwent external beam radiation therapy for prostate cancer were advised to receive periodic total colonoscopy screening annually. We evaluated the incidence and characteristics of colorectal cancer and chronic radiation proctitis. Results First, second, third, fourth and fifth total colonoscopy were performed in 256 (95%), 151 (56%), 60 (22%), 23 (8.5%) and 7 (2.6%) patients at a median of 14, 31, 42, 54 and 72 months after radiotherapy, respectively. The prevalence proportion of colorectal cancer in the first colonoscopy since radiotherapy was 3.9%. Twelve (4.4%) patients were diagnosed with colorectal cancer, including four invasive cancers, during a follow-up period. Eight of these 12 patients had not experienced rectal bleeding. The median time to diagnosis of colorectal cancer was 21 months. Chronic radiation proctitis was observed in 136 (50%) patients, including 67 (25%) patients with symptomatic bleeding. Conclusions The high detection rate of asymptomatic radiation proctitis suggests the utility of total colonoscopy to screen for early-stage colorectal cancer prior to or following radiotherapy for prostate cancer. Considering the longevity after localized prostate cancer treatment, the awareness of chronic radiation-induced proctitis and the risk of colorectal cancer masked by bleeding is needed in treatment decision -making. prostate cancer, radiotherapy, second malignancy, radiation proctitis, cancer screening Introduction External beam radiation therapy (EBRT) has favorable survival outcomes similar to that of radical prostatectomy (RP) for men with localized prostate cancer (1). Each treatment is associated with peculiar comorbidities such as rectal bleeding, urinary incontinence and sexual dysfunction. Given their longevity, long-term comorbidities, and quality of life are important for treatment decision-making of localized prostate cancer. Lower gastrointestinal tract toxicity is one of the most frequent late complications of EBRT. Ionizing radiation delivered to the rectum causes progressive fibrosis and obliterative arteritis, resulting in chronic radiation proctitis (CRP) (2). Rectal bleeding by CRP mainly occurs more than 3 months from the start of radiation to years later, lasts long-term and occasionally requires transfusion or endoscopic hemostasis (3). Recent dosage escalation has been shown to increase late gastrointestinal toxicity, while advanced treatment techniques such as intensity-modulated radiotherapy (IMRT) have been shown to decrease it (4). The reported incidence of CRP is up to 20%, in which the diagnosis is often based on a history of rectal bleeding without endoscopic evaluation (2, 5, 6). Secondary malignancy in the irradiated field is another potential comorbidity of EBRT. A meta-analysis concluded that while there was a non-negligible risk of developing second malignancies of the bladder, colon and rectum after radiotherapy for prostate cancer, the absolute rates were low (7). Other recent studies examining the risk of secondary colorectal cancer (CRC) after prostate radiotherapy show conflicting results (8–10). This uncertainty might be due to the insufficient detection of CRC. Fecal occult-blood tests (FOBT) have sufficient evidence for the screening of CRC (11); nevertheless, false-positive results are possible due to rectal bleeding after radiotherapy to the prostate. For the early and efficient detection of CRCs and surveillance of comorbidities of EBRT, in 2013, with the help of regional hospitals and clinics, our institute introduced periodic total colonoscopy (TCS) for patients receiving radiotherapy. The patients who agreed to participate in our screening colonoscopy protocol were advised to receive TCS annually after radiotherapy at regional hospitals or clinics. This retrospective investigation of the protocol aimed to clarify the incidence of CRP and sporadic CRC by screening TCS as a mid-term result. Patients and methods We retrospectively reviewed the data of all patients registered to the screening colonoscopy protocol from February 2013 to January 2018. Inclusion criteria were patients who had registered to our screening colonoscopy protocol and had a history of EBRT. To evaluate adherence to TCS, patients who had not yet received TCS were not excluded. Of the 286 cases registered to the protocol, radiotherapy was canceled after registration in four patients. Among the remaining 282 patients, one patient treated by proton therapy, two patients treated by intra-operative radiotherapy and nine patients treated by brachytherapy were excluded. We analyzed 270 patients who underwent EBRT (n = 248) or EBRT after RP (n = 22) and were advised to receive periodic TCS screening annually. This retrospective cohort study was approved by our institutional research ethics board (Number 839). Among 248 patients receiving only EBRT, 50 were treated with 70–76 Gy (2 Gy/fraction) three-dimensional conformal radiotherapy (3D-CRT). They were treated using four or six-field megavoltage X-ray beams (10MV), covering 95% of the planning target volume (PTV). PTV was created with 8 mm margin on the clinical target volume (CTV) except for the rectal wall of 6 mm margin. The remaining 181 patients received 74–78 Gy (2 Gy/fraction) IMRT and 17 patients were administered IMRT with a dose of 70 Gy (2.5 Gy/fraction). They were generally treated using 6MV X-ray beams with an image-guided technique. PTV was created with 8 mm margin on the CTV except for the rectal wall of 5 mm margin. Before or after undergoing EBRT, hormonal therapy was performed in 214 patients according to their risk of prostate cancer. Among 22 patients receiving EBRT after RP, 14 were treated with 70–74 Gy 3D-CRT and seven were treated with 70 Gy IMRT. Patient characteristics, including age at prostate cancer diagnosis, initial prostate-specific antigen (PSA) levels, Gleason score, prostate cancer stage, the use of neoadjuvant or adjuvant hormonal therapy and treatment details, were collected from medical records. The patient characteristics are summarized in Table 1. The results of TCS, including the existence of CRC, CRP and polyps were also collected from medical records. In the patients diagnosed with CRC, T stage, location, and treatment details were collected from medical records or investigated by medical referral letters. Rectal bleeding was graded according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer radiation morbidity scoring scheme (12). Symptomatic radiation proctitis was defined as Grade 1 or higher. The median follow-up time was calculated as the period after the end of EBRT for prostate cancer. Table 1 Patient characteristics . n . (%) . Patients 270 Age, years, median (range) 71 (51–82) PSA  ≤10 ng/mL 148 (55)  10–20 ng/mL 69 (26)  >20 ng/mL 53 (20) Gleason score  ≤6 19 (7)  7 165 (61)  8–10 86 (32) Stage  T1-T2a 139 (51)  T2b-T2c 82 (30)  T3a 29 (11)  ≥T3b/N1/M1 20 (7) d'Amico risk  Low 8 (3)  Intermediate 111 (41)  High 130 (48)  Locally advanced 21 (8) Hormonal therapy 214 (79) Adjuvant or salvage EBRT following RP 21 (8) Type of EBRT  3D-CRT 65 (24)  IMRT 205 (76) Total ionizing dose, Gy, median (range) 76 (70–78) Follow-up after EBRT, months, median (range) 57 (10–182) . n . (%) . Patients 270 Age, years, median (range) 71 (51–82) PSA  ≤10 ng/mL 148 (55)  10–20 ng/mL 69 (26)  >20 ng/mL 53 (20) Gleason score  ≤6 19 (7)  7 165 (61)  8–10 86 (32) Stage  T1-T2a 139 (51)  T2b-T2c 82 (30)  T3a 29 (11)  ≥T3b/N1/M1 20 (7) d'Amico risk  Low 8 (3)  Intermediate 111 (41)  High 130 (48)  Locally advanced 21 (8) Hormonal therapy 214 (79) Adjuvant or salvage EBRT following RP 21 (8) Type of EBRT  3D-CRT 65 (24)  IMRT 205 (76) Total ionizing dose, Gy, median (range) 76 (70–78) Follow-up after EBRT, months, median (range) 57 (10–182) PSA, prostate-specific antigen; EBRT, external beam radiation therapy; RP, radical prostatectomy; 3D-CRT, three-dimensional conformal radiotherapy; IMRT, intensity-modulated radiotherapy. Open in new tab Table 1 Patient characteristics . n . (%) . Patients 270 Age, years, median (range) 71 (51–82) PSA  ≤10 ng/mL 148 (55)  10–20 ng/mL 69 (26)  >20 ng/mL 53 (20) Gleason score  ≤6 19 (7)  7 165 (61)  8–10 86 (32) Stage  T1-T2a 139 (51)  T2b-T2c 82 (30)  T3a 29 (11)  ≥T3b/N1/M1 20 (7) d'Amico risk  Low 8 (3)  Intermediate 111 (41)  High 130 (48)  Locally advanced 21 (8) Hormonal therapy 214 (79) Adjuvant or salvage EBRT following RP 21 (8) Type of EBRT  3D-CRT 65 (24)  IMRT 205 (76) Total ionizing dose, Gy, median (range) 76 (70–78) Follow-up after EBRT, months, median (range) 57 (10–182) . n . (%) . Patients 270 Age, years, median (range) 71 (51–82) PSA  ≤10 ng/mL 148 (55)  10–20 ng/mL 69 (26)  >20 ng/mL 53 (20) Gleason score  ≤6 19 (7)  7 165 (61)  8–10 86 (32) Stage  T1-T2a 139 (51)  T2b-T2c 82 (30)  T3a 29 (11)  ≥T3b/N1/M1 20 (7) d'Amico risk  Low 8 (3)  Intermediate 111 (41)  High 130 (48)  Locally advanced 21 (8) Hormonal therapy 214 (79) Adjuvant or salvage EBRT following RP 21 (8) Type of EBRT  3D-CRT 65 (24)  IMRT 205 (76) Total ionizing dose, Gy, median (range) 76 (70–78) Follow-up after EBRT, months, median (range) 57 (10–182) PSA, prostate-specific antigen; EBRT, external beam radiation therapy; RP, radical prostatectomy; 3D-CRT, three-dimensional conformal radiotherapy; IMRT, intensity-modulated radiotherapy. Open in new tab We evaluated the incidence of CRC and CRP as primary endpoints. The crude CRC incidence rate was determined as the number of cases of CRC by person-years of follow-up time. The standardized incident ratio (SIR) was then calculated using Poisson regression by comparing the observed CRC incidence rates to the expected incidence rates in the Japanese age-adjusted general population in 2014 (determined from the Cancer Registry and Statistics of Japanese National Cancer Center) (13). For the calculation of SIR, only male data of the item named ‘Colorectal cancer (including carcinoma in situ)’, which was equivalent to ICD-10 code C18-C20 and D12, was utilized. The independent prognostic factors for CRC and CRP were also investigated by multivariate logistic regression analyses, and the results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Kaplan–Meier analyses from the time of the completion of EBRT for prostate cancer to the time of diagnosis of CRP were performed for all treatment modality groups. All analyses were performed using JMP version 12.2.0 (SAS Institute, Cary, NC, USA) and R version 3.5.2 (Foundation for Statistical Computing, Vienna, Austria). The threshold for statistical significance was defined as P < 0.05. Results During a median follow-up period of 57 months (range 10–182 months), 256 (95%), 151 (56%), 60 (22%), 23 (8.5%) and 7 (2.6%) patients received first, second, third, fourth and fifth TCS at a median of 14, 31, 44, 54 and 72 months after EBRT, respectively (Table 2). There were no major complications such as bleeding and perforation. CRP was identified in about 40% of patients, including about 20% of asymptomatic radiation cystitis in each periodic TCS. In the first TCS since EBRT for prostate cancer, CRC was identified in 10 patients, resulting in a CRC prevalence proportion of 3.9%. Fifty-two patients (19.3%) had received TCS before EBRT. Eight patients (3.0%) had a history of colorectal advanced neoplasia, although all of them did not suffer a relapse during the follow-up period. Table 2 Results of total colonoscopy screening . First . Second . Third . Fourth . Fifth . . n . (%) . n . (%) . n . (%) . n . (%) . n . (%) . Patients 256 151 60 23 7 Results  Colorectal cancer 10 (3.9) 1 (0.7) 1 (1.7) 0 0  Radiation proctitis 105 (41) 55 (36) 25 (42) 13 (57) 4 (57)   Symptomatic 52 (20) 32 (21) 10 (17) 5 (22) 2 (29)   Asymptomatic 53 (20) 23 (15) 15 (25) 8 (35) 2 (29)  Polyp 124 (48) 59 (39) 25 (42) 7 (30) 4 (57) Median follow-up after EBRT, months (IQR) 14 (11–19) 31 (25–41) 44 (37–54) 54 (47–61) 72 (67–84) . First . Second . Third . Fourth . Fifth . . n . (%) . n . (%) . n . (%) . n . (%) . n . (%) . Patients 256 151 60 23 7 Results  Colorectal cancer 10 (3.9) 1 (0.7) 1 (1.7) 0 0  Radiation proctitis 105 (41) 55 (36) 25 (42) 13 (57) 4 (57)   Symptomatic 52 (20) 32 (21) 10 (17) 5 (22) 2 (29)   Asymptomatic 53 (20) 23 (15) 15 (25) 8 (35) 2 (29)  Polyp 124 (48) 59 (39) 25 (42) 7 (30) 4 (57) Median follow-up after EBRT, months (IQR) 14 (11–19) 31 (25–41) 44 (37–54) 54 (47–61) 72 (67–84) EBRT, external beam radiation therapy; IQR, interquartile range. Open in new tab Table 2 Results of total colonoscopy screening . First . Second . Third . Fourth . Fifth . . n . (%) . n . (%) . n . (%) . n . (%) . n . (%) . Patients 256 151 60 23 7 Results  Colorectal cancer 10 (3.9) 1 (0.7) 1 (1.7) 0 0  Radiation proctitis 105 (41) 55 (36) 25 (42) 13 (57) 4 (57)   Symptomatic 52 (20) 32 (21) 10 (17) 5 (22) 2 (29)   Asymptomatic 53 (20) 23 (15) 15 (25) 8 (35) 2 (29)  Polyp 124 (48) 59 (39) 25 (42) 7 (30) 4 (57) Median follow-up after EBRT, months (IQR) 14 (11–19) 31 (25–41) 44 (37–54) 54 (47–61) 72 (67–84) . First . Second . Third . Fourth . Fifth . . n . (%) . n . (%) . n . (%) . n . (%) . n . (%) . Patients 256 151 60 23 7 Results  Colorectal cancer 10 (3.9) 1 (0.7) 1 (1.7) 0 0  Radiation proctitis 105 (41) 55 (36) 25 (42) 13 (57) 4 (57)   Symptomatic 52 (20) 32 (21) 10 (17) 5 (22) 2 (29)   Asymptomatic 53 (20) 23 (15) 15 (25) 8 (35) 2 (29)  Polyp 124 (48) 59 (39) 25 (42) 7 (30) 4 (57) Median follow-up after EBRT, months (IQR) 14 (11–19) 31 (25–41) 44 (37–54) 54 (47–61) 72 (67–84) EBRT, external beam radiation therapy; IQR, interquartile range. Open in new tab Table 3 Colorectal cancer and chronic radiation proctitis diagnosed by total colonoscopy screening . n . (%) . Colorectal cancer 12 (4.4)  Rectal bleeding   Grade 0 8 (3.0)   Grade 1 3 (1.1)   Grade 2 1 (0.4)  T stage   Tis 7 (2.6)   T1 3 (1.1)   T2 1 (0.4)   T3 1 (0.4)  Location   Ascending 3 (1.1)   Transverse 2 (0.7)   Sigmoid 7 (2.6)  Time to diagnosis, months, median (range) 21 (10–50) Chronic radiation proctitis 136 (50)  Rectal bleeding   Grade 0 69 (26)   Grade 1 40 (15)   Grade 2 27 (10)  Endoscopic hemostasis 15 (5.6)  Time to diagnosis, months, median (range) 14 (3–109) . n . (%) . Colorectal cancer 12 (4.4)  Rectal bleeding   Grade 0 8 (3.0)   Grade 1 3 (1.1)   Grade 2 1 (0.4)  T stage   Tis 7 (2.6)   T1 3 (1.1)   T2 1 (0.4)   T3 1 (0.4)  Location   Ascending 3 (1.1)   Transverse 2 (0.7)   Sigmoid 7 (2.6)  Time to diagnosis, months, median (range) 21 (10–50) Chronic radiation proctitis 136 (50)  Rectal bleeding   Grade 0 69 (26)   Grade 1 40 (15)   Grade 2 27 (10)  Endoscopic hemostasis 15 (5.6)  Time to diagnosis, months, median (range) 14 (3–109) Open in new tab Table 3 Colorectal cancer and chronic radiation proctitis diagnosed by total colonoscopy screening . n . (%) . Colorectal cancer 12 (4.4)  Rectal bleeding   Grade 0 8 (3.0)   Grade 1 3 (1.1)   Grade 2 1 (0.4)  T stage   Tis 7 (2.6)   T1 3 (1.1)   T2 1 (0.4)   T3 1 (0.4)  Location   Ascending 3 (1.1)   Transverse 2 (0.7)   Sigmoid 7 (2.6)  Time to diagnosis, months, median (range) 21 (10–50) Chronic radiation proctitis 136 (50)  Rectal bleeding   Grade 0 69 (26)   Grade 1 40 (15)   Grade 2 27 (10)  Endoscopic hemostasis 15 (5.6)  Time to diagnosis, months, median (range) 14 (3–109) . n . (%) . Colorectal cancer 12 (4.4)  Rectal bleeding   Grade 0 8 (3.0)   Grade 1 3 (1.1)   Grade 2 1 (0.4)  T stage   Tis 7 (2.6)   T1 3 (1.1)   T2 1 (0.4)   T3 1 (0.4)  Location   Ascending 3 (1.1)   Transverse 2 (0.7)   Sigmoid 7 (2.6)  Time to diagnosis, months, median (range) 21 (10–50) Chronic radiation proctitis 136 (50)  Rectal bleeding   Grade 0 69 (26)   Grade 1 40 (15)   Grade 2 27 (10)  Endoscopic hemostasis 15 (5.6)  Time to diagnosis, months, median (range) 14 (3–109) Open in new tab Twelve (4.4%) patients were diagnosed with CRC, including four (1.5%) pT1 or deeper invasive cancers (Table 3). Two of these four patients with invasive cancers underwent colectomy and had not developed a recurrence. Eight of these 12 patients had not experienced rectal bleeding or diagnosis of CRP and were incidentally diagnosed by periodic TCS. Almost all detected cancers were located outside the irradiated field (no cancers in the rectum). The median time to diagnosis was 21 months (range 10–50) after EBRT. The crude overall incidence rate of CRC was 916 per 100000 person-years (95% CI 473–1601). The SIR was 2.74 (95% CI 1.41–4.78), comparing the expected CRC incidence rates in the Japanese age-adjusted general population. Multivariate logistic regression analyses identified no clinical predictors for CRC (Table 4). Table 4 Prognostic factors of colorectal cancer and chronic radiation proctitis . Univariate . Multivariate . Factors . P value . Odds ratio (95% CI) . P value . Risk for colorectal cancer  Age 0.79  d'Amico risk* 0.65  Hormonal therapy 0.57  Type of EBRT** 0.22  Total ionizing dose 0.92 Risk for chronic radiation proctitis  Age 0.96  d'Amico risk* 0.72  Hormonal therapy 0.40  Type of EBRT** 0.012 2.06 (1.17–3.69) 0.012  Total ionizing dose 0.67 . Univariate . Multivariate . Factors . P value . Odds ratio (95% CI) . P value . Risk for colorectal cancer  Age 0.79  d'Amico risk* 0.65  Hormonal therapy 0.57  Type of EBRT** 0.22  Total ionizing dose 0.92 Risk for chronic radiation proctitis  Age 0.96  d'Amico risk* 0.72  Hormonal therapy 0.40  Type of EBRT** 0.012 2.06 (1.17–3.69) 0.012  Total ionizing dose 0.67 *High—Locally advanced vs. Low—Intermediate **IMRT vs. 3D-CRT CI, confidence interval; EBRT, external beam radiation therapy; IMRT, intensity-modulated radiotherapy; 3D-CRT, three-dimensional conformal radiotherapy. Open in new tab Table 4 Prognostic factors of colorectal cancer and chronic radiation proctitis . Univariate . Multivariate . Factors . P value . Odds ratio (95% CI) . P value . Risk for colorectal cancer  Age 0.79  d'Amico risk* 0.65  Hormonal therapy 0.57  Type of EBRT** 0.22  Total ionizing dose 0.92 Risk for chronic radiation proctitis  Age 0.96  d'Amico risk* 0.72  Hormonal therapy 0.40  Type of EBRT** 0.012 2.06 (1.17–3.69) 0.012  Total ionizing dose 0.67 . Univariate . Multivariate . Factors . P value . Odds ratio (95% CI) . P value . Risk for colorectal cancer  Age 0.79  d'Amico risk* 0.65  Hormonal therapy 0.57  Type of EBRT** 0.22  Total ionizing dose 0.92 Risk for chronic radiation proctitis  Age 0.96  d'Amico risk* 0.72  Hormonal therapy 0.40  Type of EBRT** 0.012 2.06 (1.17–3.69) 0.012  Total ionizing dose 0.67 *High—Locally advanced vs. Low—Intermediate **IMRT vs. 3D-CRT CI, confidence interval; EBRT, external beam radiation therapy; IMRT, intensity-modulated radiotherapy; 3D-CRT, three-dimensional conformal radiotherapy. Open in new tab Overall, CRP was observed in 136 (50%) patients, including 67 (25%) patients with symptomatic bleeding (Table 3). The median time to diagnosis was 14 months. Fifteen patients (5.6%) required endoscopic hemostasis. The cumulative incidence rate of total CRP and symptomatic CRP within five years were 52 and 29%, respectively (Fig. 1). The type of EBRT (IMRT vs. 3D-CRT) was independently associated with the development of CRP in multivariate logistic regression analyses (OR 2.06, 95% CI 1.17–3.69). Figure 1. Open in new tabDownload slide Kaplan–Meier analysis of the cumulative incidence rate of total radiation proctitis and symptomatic radiation proctitis. Figure 1. Open in new tabDownload slide Kaplan–Meier analysis of the cumulative incidence rate of total radiation proctitis and symptomatic radiation proctitis. Discussion The results of the current study revealed a high incidence of latent CRP by periodic TCS screening after EBRT for prostate cancer. As the number of TCS increased, so did the cumulative incidence rate of CRP. Five years later, half of the patients had been diagnosed with CRP, and half of the patients with CRP had not experienced rectal bleeding. Most previous reports on CRP following prostate EBRT were mainly by interview or questionnaire; to our knowledge, ours is the first study to perform this investigation using comprehensive TCS. The reported incidence of CRP was up to 20%, equivalent to the incidence of symptomatic radiation proctitis in our cohort (5, 6). For fecal occult-blood tests after EBRT for prostate cancer, microscopic bleeding due to radiation proctitis potentially affects the results even without a bloody stool. While the effectiveness of FOBT to screen CRC is widely accepted (11, 14), it is known that multiple risk factors are associated with a false-positive or false-negative result (15). The effect of pelvic radiotherapy on the false-positive result of FOBT had not been well evaluated because some studies regarding colonoscopy and FOBT excluded patients with CRP. On the other hand, Muinuddin et al. reported that false-positive results of FOBT had included cases with radiation proctitis (16). FOBT screening may be useful by its high sensitivity even if the state after the radiation therapy to the prostate; however, a careful interpretation of the results and consideration to perform colonoscopy are needed. In the present study, most of the CRCs were identified in the first TCS and only 19% of patients in this study cohort had received TCS before EBRT, which indicated the possibility of synchronous cancer. Exposure to ionizing radiation is generally considered to have carcinogenic potential. Ionizing radiation induces DNA damage and subsequently leads to gene mutations and malignant transformation (17). A recent meta-analysis concluded that radiotherapy for prostate cancer resulted in a significantly high risk of CRC compared with no radiotherapy or surgery (7). The increased risk of rectal cancer after EBRT for prostate cancer might depend on its close anatomical relationship to the prostate and a tendency for radiation toxicity usually represented as proctitis (18). It is highly suggested most of the CRCs found in this study were not radiation induced, considering a latency period of at least 5 years before the development of solid radiation-induced CRC based on studies of atomic bomb survivors or patients following pelvic radiotherapy for ovarian cancer (19, 20). We have recommended patients to receive TCS before EBRT since September 2014, and further follow-up is needed to confirm whether CRC had coexisted before EBRT. The epidemiologic and etiologic association between prostate cancer and second primary CRC remains controversial (9). In Australia, Heard et al. noted an increased risk of CRC following a prostate cancer diagnosis, whereas Davis et al. noted a reduced risk of subsequent CRC in the Surveillance, Epidemiology and End Results (SEER) database (21, 22). Genetic associations such as BRCA1/2 and Lynch syndrome have also been reported between CRC and prostate cancer (23, 24). Regarding the prevalence of CRC in patients scheduled EBRT for prostate cancer, Nakano et al. reported that seven of 307 patients (2.3%) were diagnosed with CRC before EBRT (25). Ko et al. reported that nine of 161 patients (5.6%) in Korea were diagnosed with CRC by TCS within one year of a prostate cancer diagnosis; however, the treatment was not evaluated (26). The detection rate of CRC of the first TCS in the present study was 3.9%, which was about the same as that of those previous reports. On the other hand, Quintero et al. reported that one-time TCS detected invasive CRC and advanced adenoma in 0.1 and 1.9% of asymptomatic general adults 50 to 69 years of age, respectively (14). The high detection rate of CRC in this study is thought to be explained by self-selection bias based on a low CRC screening rate in the Japanese general population. The results in this study could not conclude the increase of radiation-induced CRC but imply the importance of sufficient detection of CRC prior to or following EBRT for prostate cancer. The limitations of the present study include its single-arm retrospective observational nature, the relatively small sample size with self-selection bias, and short follow-up time. The screening colonoscopy protocol did not limit participants to pre-radiotherapy patients or force them to undergo TCS, which may have resulted in a selection bias. Patients with bloody stool or eagerness to receive general checkups may be prone to receiving more frequent TCS. Larger numbers of patients and longer follow-up durations are necessary to clarify the association between prostate EBRT and CRC. However, TCS in the early post-radiotherapy period helps early detection of CRC, which allowed patients with CRC to receive appropriate treatment as well as favorable survival outcomes. Radiation-induced chronic inflammation is slowly developed and hardly recovered, and the risk of secondary cancers after EBRT increases over time (8). Since long-term survival is common after treatment for localized prostate cancer, the American Cancer Society Prostate Cancer Survivorship Care Guidelines support the need for follow-up screening guidelines for individuals at higher risk of CRC (27). Although the benefit of TCS for CRC screening in the average-risk population is uncertain (14, 28), a randomized controlled trial for the utility of TCS screening in Japanese general population is also actively evaluating and results are awaited (29). Based on recent guidelines for screening colonoscopy, the frequency of TCS of our protocol appears to be excessive especially in the patients with negative findings on baseline colonoscopy (30). The frequency, interval and cost-effectiveness should be considered referring to future studies about TCS screening. 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TI - Screening of chronic radiation proctitis and colorectal cancer using periodic total colonoscopy after external beam radiation therapy for prostate cancer
JF - Japanese Journal of Clinical Oncology
DO - 10.1093/jjco/hyab056
DA - 2021-04-23
UR - https://www.deepdyve.com/lp/oxford-university-press/screening-of-chronic-radiation-proctitis-and-colorectal-cancer-using-WWZYltQkd7
SP - 1
EP - 1
VL - Advance Article
IS - 
DP - DeepDyve
ER -