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Rectal Cancer - 2005 M62 Coloproctolgy course, Huddersfield. Lars Påhlman Dept Surgery, Colorectal unit University Hospital, Uppsala, Sweden. Why focus on surgery ? The only curative option Big variation among surgeons Training mandatory
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Rectal Cancer - 2005M62 Coloproctolgy course, Huddersfield Lars Påhlman Dept Surgery, Colorectal unit University Hospital, Uppsala, Sweden
Why focus on surgery ? The only curative option Big variation among surgeons Training mandatory Surgical strategy important Rectal Cancer - focus on surgery
Two main options Local excision Abdominal resection Rectal cancer surgery
TEM surgery - adenomas Transanal Endoscopic Microsurgery • Full thickness excision • Up to 20 cm • Perfect view
Local excision T 1 tumours ‘Early’ T 2 tumours ‘Any T’ fragile patients TEM - technique crucial Rectal cancer surgery
Local tumour control Mesorectum Lateral spread Intramural spread Implantation metastases Nodal involvement Rectal cancer surgery
Standard surgery TME the gold standard Rectal Cancer - focus on surgery
Lateral resection margins Local recurrences / number of patients Pos. lat. marg. Neg. lat. marg. 11/13 (85%) 1/38 (3%) p < 0.001 Quirke et al. Lancet, nov 1; 1986 Rectal cancer surgery
Intramural spread Hardly ever extend more than 0.5 cm Grinell R. Surg Gynecol Obstet 99: 421-430; 1954 Rectal cancer surgery
5 years follow-up (1995 - 97) Local recurrence rate Irrigation Ant. Resection Hartmann Yes 96 / 1464 7 % 8 / 71 11 % No 44 / 398 11 % 11 / 115 10 % Unknown 7 / 65 11 % 1 / 17 6 % p < 0.001n.s. Swedish Rectal Cancer Register
Nodal involvement Proximal Lateral Distal Rectal cancer surgery
Proximal lymph node clearance High-tie No effect on survival + nodes = disseminated disease Grinell; Surg Gynecol Obstet 120:1031, 1965 Pezim and Nicholls; Ann Surg 200:729, 1984 Rectal cancer surgery
Lateral lymph node clearance Super radical surgery Extended pelvic lymphadenectomy Retro-peritoneal clearance Extra mesenteric clearance Hojo et al; Dis Colon Rectum 32:307, 1989 Rectal cancer surgery
Lateral lymph node clearance Super radical surgery Positive nodes indicates disseminated disease Hojo et al; Dis Colon Rectum 32:307, 1989 Rectal cancer surgery
Lateral lymph node clearance Morbidity Impotence > 60 % Voiding problem > 40 % Prolongs surgery Rectal cancer surgery
Lateral lymph node clearance The pivotal trial ! TME + lateral LN clearance vs Neo - adj. irrad. + TME Rectal cancer surgery
Rectal cancer surgery Distal lymph node clearance Total mesorectal excision How important ? Heald et al; Br J Surg 1982
Distal lymph node clearance Total Mesorectal Excision In all cases ? What is the upper limit ? Morbidity increased ! Rectal cancer surgery
Low rectal cancers Abdominoperineal Excision Very difficult surgery ! Important to have correct strategy Avoid ‘coning’ ! Start early from below ! Rectal cancer surgery
Conclusion Well - trained surgeons ! TME gold standard ! Lateral lymph nodes - radiotherapy APR very tricky ! Cone - effect must be avoided Rectal cancer surgery
Role of radiotherapy in rectal cancer • To lower local failure rates and improve survival in resectable cancers • To allow surgery in non-resectable cancers • To facilitate a sphincter-preserving procedure in low-lying cancers ? • To cure patients without (major) surgery
Meta-analysis rectal cancer radiotherapy 22 trials, 8 507 patients Reduction in overall colorectal isolated mortality cancer deaths local recurr. Preoperative: BED <20 Gy ns ns ns 20 - 30 Gy ns ns 24 ± 15 30 - 37.5 Gy 10±5* 22 ± 5**** 57 ± 7**** Postoperative: BED 35 - 44 Gy ns 9 ± 7 (ns) 33 ± 11**
Radiotherapy in resectable cancer • Conclusions from the meta-analysis • Radiotherapy works (with standard surgery) • lowers local failure rates • improves survival • Dose-response relationship (for preop RT) • low doses ineffective • Preop RT is more dose-efficient than postop seen in the Uppsala-trial comparing pre- and postop RT
Neoadjuvant radiotherapy will always reduce the local recurrence rate with 50 % Irrespective of type of surgery Rectal Cancer Surgery
Type of surgery Local recurrence RT - RT + ‘sloppy’ 30 % 10 % TME 13 % 6 % Rectal Cancer Surgery
Radiation schedule Conventional fractionation: 45 - 50 Gy in 4 - 5 weeks Accelerated fractionation: 25 Gy in 1 week Adjuvant radiotherapy
Ongoing trial in Sweden 3-armed trial 25 Gy / 1 week immediate surgery 25 Gy / 1 week delayed surgery 50 Gy / 5 weeks delayed surgery Adjuvant radiotherapy
Dutch trial - Local recurrencePatients with R 0 (n=1789) TME alone 5.8% vs 11.4% p < 0.001 RT + TME
Overall Survivaleligible patients (n=1809) TME alone 64.2% vs 63.4% p = 0.87 RT + TME
Cancer specific survivaleligible patients (n=1809) 76.1% vs 73.0% p = 0.18
Dutch trial - Local recurrence rateLevel from the anal verge 0 - 5 cm 6 - 10 cm 11 - 15 cm 10.5% vs 11.9% p = 0.53
Local recurrence rate (min. 5 years) (patients operated on for cure) Preop. irrad . Surgery alone p-value Ant. res. 9 % (18 / 206) 21 % (41 / 194) < 0.001 Abd. per. 9 % (22 / 243) 25 % (65 / 256) < 0.001 Other op. 33 % ( 2 / 6 ) 38 % ( 3 / 8 ) SWEDISH RECTAL CANCER TRIAL
Trial / level Local recurrence RT - RT + p value SRCT < 5 cm 27 % 10 % 0.003 TME < 5 cm 11 % 12 %0.53 SRCT 6 - 10 cm 26 % 9 % < 0.001 TME 6 - 10 cm 15 % 4 % < 0.001 SRCT > 10 cm 12 % 8 % 0.3 TME > 10 cm 6 % 4 % 0.15 Local recurrence rate
Data report 1995 - 2004 15,000 patients ( 1,500 yearly) Base - line data Trends in treatment 5-year oncological data Swedish Rectal Cancer Register
Local recurrence % (1995 - 98) All patients R 0 surgery
Local recurrence % (1995 - 1997) 0 - 6 cm 7 - 15 cm
Rectal cancer treatment - what have we learned ? • Local failures can more or less be eliminated; < 3 % (not only 10 %) • Survival slightly improved about 10 % with some morbidity (TME + RT) • The challenge is to preoperatively find those who need more than surgery and predict where the tumour cells are (to use radio- therapy on an individual level)
Preoperative chemo-radiotherapyin rectal cancer Is RT/CT superior to RT in resectable rectal cancer ? Probably, but the evidence is low Two ! trials are ongoing (EORTC) (France)
Non-resectable Must be identified preop. Malpractice if not treated with preoperative irradiation Rectal cancer
Non-resectable rectal cancer • No uniform definition (T4’s growing into a another often non-resectable organ/tissue) • 10 - 15%, half without distant metastases • Causes much suffering • Surgery alone likely cures very few • Preop. prolonged radio(chemo)therapy is mandatory