Radiotherapy and Oncology, 17 (1990) 275-283
Elsevier
275
RADION00673
Present status of radiation therapy in the conservative management of rectal cancer J. Papillon Centre L~on B~rard, Lyon, France (Received 3 January 1989, revision received 9 May 1989, accepted 2 October 1989)
Key words: Rectal cancer; Conservation; Radiotherapy
Summary Conservative treatment of rectal cancer may be a valid alternative to radical surgery in cases selected with regard to their very low probability of lymphatic spread. Beside the surgical modalities of local treatment, radiation therapy has gained a substantial place thanks to the use of intracavitary irradiation (contact X-ray therapy and interstitial curietherapy). In a series of 310 cases of T1-T 2 tumors followed more than 5 years, the rate of death of cancer is 7.7 ~o and the rate of local failures is 5 ~o, significantly inferior to that following local excision or electrocoagulation. Moreover, in elderly poor risk patients with T2 or T 3 tumors of the lower third of the rectum, it is possible to extend somewhat the field of conservative treatment without jeopardizing their chance of cure. The protocol is based on a short but intensive course of external beam irradiation (30 Gy over 12 days) followed 2 months later by intracavitary irradiation directed to the tumor bed. The purpose of this strategy is a tentative conversion of low-lying tumors suitable for abdominoperineal resection into lesions amenable to conservation. In a series of 71 patients (mean age 74 years) with selected T 2 or T 3 tumors larger than 4 cm, followed more than 3 years, the rate of death of cancer is 11~o and the rate of death of intercurrent disease is 22~o. At 5 years the rate of death of cancer is 16 ~o. It is emphasized the necessity of a strict selection of cases by clinical means and endorectal sonography. This strategy must only be conceived as a teamwork of radiation therapists and surgeons.
Introduction Conservative treatment of rectal cancer has long been considered as a dangerous heresy. Most Address for correspondence: J. Papillon, Centre Lron Brrard, 28 Rue La~nnec, 69008 Lyon, France.
surgeons were reluctant to perform limited operations, fearing that such procedures might not be curative and rightly regarding cure as more important than the avoidance of a colostomy. During the past decade there has been significant changes of opinion and, although major surgery remains the conventional approach to rectal
0167-8140/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)
276 cancer, conservative procedures have gained a place in the management of low-lying tumors as an alternative to radical surgery. These changes are due to progress in the knowledge of the clinical behavior of the tumor, of the prognostic value of histological grading and of the relationship between local and regional spread. Local treatment should only be considered if the long-term results are at least equal to those of major surgery. That implies that rectal cancers submitted to conservative treatment should be a local disease with a very low probability of lymphatic involvement. This rule is the key factor of the case selection. Irrespective of the method used, the selection is based on several criteria: (1) Histological grading based on multiple biopsies. Only well- and moderately well-differentiated adenocarcinomas may be accepted. (2) Local spread. Morson and Bussey [20] have shown that until penetration of the rectal wall has taken place the chance of lymphatic metastases having already occurred is very low in the range of 6~o. They estimated that these lesions may be considered with a high probability as a local disease and submitted to a local treatment. This statement, which has been confirmed by Hermanek [12] and Turnbull [32], indicates that T1 and some T 2 tumors may be treated locally. Can one stage a cancer accurately before treatment? Up to the last few years the clinician was considered to be unable to have a clear idea of the extent of a tumor. Contrarily, York Mason [36] and Nicholls et al. [22] comparing clinical and pathological data have demonstrated that the clinician, as long as the examination is made carefully, can assess the local spread of a palpable tumor quite accurately. He bases his findings not only on the mobility, which is the most important sign of penetration of the bowel but also on the configuration of the growth, its consistency and its histological grading. Endorectal sonography has improved this preoperative clinical staging significantly [2]. Compared to the data drawn from operative
specimens, endorectal sonography has an overall correlation coefficient of 90~o. This method can predict invasion beyond the muscularis propria with a sensitivity and specificity of about 95 ~o. It is capable of differentiating between inflammatory and malignant infiltration. This brings a new objectivity to an area previously hampered by the subjectivity of digital examination. Endorectal sonography has also the advantage to explore tumors which are not within reach of the examining finger and discover pararectal lymph nodes. By the visualization of all layers of the rectal wall it allows the precise allocation of tumors into the U.I.C.C. groups T1-T4. This method is especially useful in the selection of early T1-T2 invasive, non-pedunculated tumors which can be suitable for conservation treatment. This role of endorectal sonography is so important that local treatment should be undertaken according to the findings of this investigation. (3) Tumor size. Almost all investigators consider that the tumor should not be more than 4 cm in diameter. (4) Accessibility. Most if not all tumors submitted to local treatment may be palpated and are situated in the low- or mid-rectum and easily accessible by transanal approach. (5) Absence of detectable perirectal metastatic lymph nodes. Careful palpation preferably with the patient in the knee-chest position and endorectal sonography are valid means in this systematic search. Pretreatment evaluation must include CT scan of the abdomen and pelvis, CEA level, colonoscopy or double contrast barium enema and general examination to make sure that there is neither distant metastasis nor synchronous colonic carcinoma. Lastly, when a conservative modality has been used it is essential that the patient be followed up closely. The patient must understand the necessity of regular follow-up examinations. If persistence or recurrence of the tumor is discovered in its early stages the radical surgery can be carried out with success in many cases.
277 Material and methods Two modalities of radiotherapy may be used to control rectal tumors.
(1) Intracavitary irradiation Under this heading one must include the contact X-ray therapy with the 50 kV Philips machine and the interstitial curietherapy with iridium-192. These methods represent the most known techniques of local therapy by irradiation [24,25]. Contact X-ray therapy, which is the basic method always used first, is an ambulatory treatment carried out in the out-patient department. It consists of four applications within 6 weeks. During the treatment the radiotherapist wears a leaded rubber apron and a leaded rubber left glove. The X-ray tube is held by its handgrip in his right hand and is fitted in the treatment applicator, which is firmly held by his left hand. The very short time of the application (less than 2 min) and the practical tube construction allows the radiotherapist to "shoot" this radiation as would a pistol. Between each application there is an inter-
val of 1-3 weeks. Usually the treatments take place on days 1, 8, 22 and 43. The overall dose delivered is 100-120 Gy. High doses (20-30 Gy) of low voltage irradiation given at every treatment produce a rapid shrinkage of the exophytic part of the tumor. Hence at the second application, the tumor has usually a greatly reduced volume compared with its initial size. The same process is noticed at subsequent applications, the tumor being destroyed layer by layer. Iridium-192 implant is a supplementary modality, which aims at delivering a booster dose of 20 Gy in 24 h to the tumor bed. The implantation of an iridium fork with two prongs 4 cm long and 16 mm apart is performed under local anesthesia and takes place 4 - 6 weeks after completion of contact X-ray therapy. The experience of the Centre L6on B6rard includes 310 patients treated between 1951 and 1983 with no lost to follow-up. All patients had true invasive well- or moderately well-differentiated sessile adenocarcinoma. Carcinomas in situ, cancers in polyp and degenerated villous tumors were excluded (Tables I and II).
TABLE 1 Intracavitary irradiation of cancer of the rectum contact X-ray therapy + iridium-192: series of the Centre L6on B6rard, Lyon. No. of cases
5-Year survival NED
Death of cancer
Death of intercurrent disease
Postoperative death
310
229 (73.8%)
24 (7.7%)
53 (17%)
4 (0.6%)
TABLE II Pelvic failures after intracavitary irradiation of rectal cancer: series of 310 cases.
No. of cases Local failures Nodal failures
Alive and well
14 (4.5%) 12 (3.8%)
4 3 , ; LI
•i~
'
Death of cancer
Postoperative death
9 8
1 1
278
(2) Combined external beam and intracavitary irradiation in a split-course regimen Intracavitary irradiation, which is applicable to less than 10~o of rectal cancers is not the only means of conservative treatment by irradiation. The purpose of the new protocol, which will be described, aims at extending the field of conservation by irradiation without jeopardizing the chance of cure. The efficacy of external beam irradiation depends on the dose-time relationship and may be evaluated by the study of the operative specimens. Since 1977, a particular modality of preoperative irradiation has been used at the Centre Lron Brrard. It consists of a short but intensive course of irradiation with cobalt-60 using a 120 ° arc rotation through a sacral field. A dose of 30 Gy is delivered in 10 fractions within 12 days. The isodose distribution shows that a hot spot (35 Gy) is given to the tumor area. The main characteristics of the method, which has been previously described [24] are as follows: (1)limited targetvolume, which includes the most important sites of regional spread of rectal cancer; (2)satisfactory protection of the small bowel thanks to the bladder distension. The tolerance is good: proctitis does not last more than 3 weeks and is easily relieved by steroid enemas. The surgical decision was taken after an interval of 2 months. The 2-month rest enlightens the selection process and the downstaging of many tumors may be evaluated according to 127 operative specimens (Table III). These data must be taken into consideration when the clinician is facing a particular problem represented by poor risk patients with T 2 o r T 3 TABLE III Preoperative irradiation and surgery 2 months later: operative specimens. No. of cases
Tumor-free
Dukes' A
Dukes' B
Dukes' C
127
18%
35%
21%
25%
cancers, too large, too infiltrating or too close to the anus to be treated by usual conservative methods. In such cases it is rational to try to convert some tumors of the lower third of the rectum from radical excision into lesions amenable to conservative treatment by using external beam irradiation (30 Gy within 12 days) followed 2 months later by intracavitary irradiation - one application of contact X-ray therapy (25 Gy) and an iridium-192 implant (20-30 Gy). This splitcourse irradiation is only applicable in T 2 or some T 3 tumors selected with regard to histological grading (I or II) and local spread assessed by clinical means and endorectal sonography, which must show no or slight extrarectal spread and no detectable pelvic metastatic nodes. The last but not the least condition is the substantial shrinkage of the tumor at the end of the second month leaving a limited and superficial residual disease suitable for local therapy. This protocol has been applied between 1977 and 1984 to 71 patients (median age 74 years).
Results
Two groups of patients will be studied according to the treatment modality used.
(1) Intracavitary irradiation In the series of 310 patients followed for more than 5 years, immediate tolerance was always good. When the irradiation treatment is finished, most patients do not have any local reaction. Some have a slight proctitis which does not last more than 3 weeks. Superficial radionecrosis is rare (5~o), most of them are asymptomatic and heal spontaneously. Usually follow-up reveals some atrophy of the mucosa. Intracavitary irradiation never gives rise to stricture or narrowing of the rectal lumen, which keeps its normal size and consistency making digital examination particularly easy at subsequent visits. During the follow-up period, occasional bleeding may alarm patients. These episodes due to telangiectasia
279 may require the use of laser applications. Out of the 229 patients alive and well more than 5 years after treatment, 221 have a normal anal function and 8 have a permanent colostomy. The rate of death of cancer is 7.7~o and of intercurrent disease 17~o (Table I). Distant metastases without pelvic disease were observed in seven cases (2 ~ ) . Local failures were seen in 14 patients (4.5 ~o), 9 underwent a radical excision, of them four have been saved and one died postoperatively. Among the 12 patients who developed pelvic metastatic lymph nodes (3.8 ~o) 10 were operated on, of them three have been saved by surgery, either APR (one case) or perirectal lymphadenectomy wihout bowel resection (two cases) (Table II). In the whole group of 26 patients with local or nodal failures, seven were not operated upon because of their poor general condition and/or of the extent of the disease, which was considered to be unresectable. It must be added that five patients with presumed local failure underwent an APR, the operative specimen being tumor-free. Two of them died postoperatively, three are alive and well. The high rate of death of intercurrent disease and the high proportion of postoperative death 4 out of 23 patients operated (17~o) - are the proof that many patients submitted to intracavitary irradiation were poor risk and elderly with a short expectation of life. In the whole series, twothird of patients had polypoid, protuberant tumors, and one third had ulcerative lesions. Among the patients who died of cancer, 11 (45 ~o) had an ulcerative tumor. In the interpretation of these figures it must be taken into consideration that this series dates from a period when endorec-
tal sonography was not available and that some of the cases treated were borderline indications of intracavitary irradiation alone and should have required a different strategy such as the combined irradiation. (2) Combined external beam and intracavitary irradiation Seventy-one elderly poor risk patients with T z or T 3 well- or moderately well-differentiated adenocarcinoma of the lower third of the rectum underwent a combined irradiation. The tumors were considered not suitable for intracavitary irradiation because of their size, their degree of infiltration or penetration of the rectal wall or their location in the juxta-anal area. The minimum follow-up is 3 years. Forty-six (64.7~o) are alive and well, 44 of them with a normal anal function, two with permanent colostomy for local failure. Among the 8 patients who died of cancer, 3 had distant metastasis, 5 died of pelvic failure. One 84-year-old patient died after an APR for local failure. At 5 years the rate of death of cancer is 16 ~o, whereas the death of intercurrent disease is 28 ~o. This figure is due to the poor general condition of most patients. The tolerance of this treatment was generally good. Benign and superficial radionecrosis which healed spontaneously was observed in five cases (Table IV).
Discussion
There are three main methods of conservative treatment: local excision, electrocoagulation and
TABLE IV Tentative conversion of T2, T 3 low-lying tumors from radical excision into conservative treatment in poor risk patients by split-course external beam irradiation and intracavitary irradiation.
At 3 years At 5 years
No. of cases
Alive and well
Death of cancer
Death of intercurrent disease
Postoperative death
71 49
46 (64%) 26 (53%)
8 (11%) 8 (16%)
16 (22%) 14 (28%)
1 1
280 TABLE V Local excision for rectal cancer. Author
No. of cases
Rate of local failures (~o)
Hawley and Ritchie [ 11] Hermanek et al. [12] Deucher and Nothiger [9] Stearns et al. [30] York Mason [36] Biggers et al. [3] Whiteway et al [34]
42 48 34 31 41 141 42
20 10 11 25 7 27 16
irradiation. At St. Mark's Hospital, the percentage of local excisions gradually increased from 1~o in 1948 to 9 ~ in 1975. The principal statistics of local excision are reported on Table V. Electrocoagulation was popularized by Jackman [13] in 1961. The most important series are reported on Table VI. The first treatments by intrarectal contact X-ray therapy with the Philips unit were made by Lamarque [ 15] in Montpellier, France in the 1940s. The development of the method dates from 1951 in Lyon [23,25]. The first applications in the U.S.A. date from 1973 by Sischy [29], who treated 192 cases followed for 1 to 14 years. In this series the rate of local failures is 5 ~o, similar to that of our own series. During the past few years several investigators have published their experience of intrarectal application of the 50 kV Philips machine. Myerson et al. [21] reported on 57 cases followed for 1 to 6 years with 30~o of local failures. Lavery et al.
[17] published 62 cases followed from 2 to 13 years with 18~o of local failures. Kovalic [14] reported on 32 cases followed from 1 to 9 years with 2 4 ~ of local recurrence. The high rates of local failures in the most recent studies compared with the results obtained at the Centre Lron Brrard and by Sischy can only be explained by differences both in case selection and in radiotherapy technique. Dose fractionations also differ markedly from the original technique. Iridium192 implant, which certainly increases the chance of tumor control, is almost never mentioned in the recent series. It is all the more difficult to compare surgical and radiotherapeutic methods of local therapy as there are great differences in the rates of success among the series of local excision (Table V) and among the series of electrocoagulation (Table VI) although the criteria of selection are apparently similar. As far as the radiotherapy is concerned, some points may be emphasized. (1) Cancer of the rectum is radiosensitive enough to be controlled at its early stage by irradiation alone. (2) Intracavitary irradiation properly applied strict selection of early rectal cancer, careful technique - is highly curative with a rate of local failures in the range of 5~o, significantly lower than those reported in most statistics of local excision or electrocoagulation. (3) Contact X-ray therapy has a progressive and selective action. Irradiation has a differential effect related to the degree of radio-sensitivity of
TABLE VI Electrocoagulation for rectal cancer. Author
No. of cases
Rate of local faillures ( ~ )
Crile and Turnbull [6], Turnbull [32] Culp [7] Madden [19] Salvati et al. [28] Lasser et al. [16] Lazorthes et al. [18]
62 67 175 81 20 20
13 25 23 38 5 5
281 neoplastic and normal tissues. The four applications of X-rays are separated by interval of 1-3 weeks. During this period, the response of the tumor to treatment is used as a guide to identify the appropriate target-volume and the dose to be delivered. The progressive action is the key factor of success of the method. (4) Intracavitary irradiation may be applied to tumors of the anterior wall of the rectum in female patients or at the level of peritoneal reflexion without risk of perforation or fistula. (5) The scar after irradiation is supple or slightly fibrotic without any narrowing of the rectal lumen, making follow-up examination particularly easy, whereas the scar after electrocoagulation is often hard and retracted with some degree of stricture formation. (6) The percentage of metastatic lymph nodes observed during the follow-up is in the same range as the probability of lymphatic spread mentioned by Morson and Bussey [20] for T~ and T 2 wellor moderately well-differentiated adenocarcinomas.
At present, intracavitary irradiation is able to control most T~ tumors not larger than 4 cm in diameter. Limited T 2 lesions may also be controlled by intracavitary irradiation, but the experience of the protocol combining external beam and intracavitary irradiation in a split-course regimen urges us in case of ulcerative T 2 carcinomas or of cancers located in the juxta-anal area to apply this modality rather than intracavitary irradiation alone. Many reports devoted to preoperative irradiation have shown that some patients with T 2 o r T 3 tumor have a specimen free of tumor cells, especially when surgery takes place more than 3 weeks after completion of irradiation [4,5,24,25,29,31,33,35]. Theoretically, the 23 patients of our series with tumor-free specimens could have been spared major surgery. Among the 45 patients with Dukes' A specimen, 10 had only microresidual disease which could have been possibly controlled by a local method. These examples indicate that external beam ir-
radiation may be more effective than expected. Wang and Schulz [33] in 1962 were among the first to report cure at 5 years after external beam irradiation alone and considered that 6 of their 58 inoperable patients may have been cured in this way. Rider et al. [26] and Cummings [8] showed that protracted irradiation is able to control mobile tumors in 38~o of cases. They emphasized that the tumor response is particularly slow and that an early decision may be inadequate. In these series external beam irradiation was used alone, whereas in our study the booster dose given by intracavitary irradiation after an interval of 2 months increases substantially the efficacy of radiotherapy. Conservative treatment may be applied to middle-aged patients with early rectal cancer but in patients older than 70 with T 2 or T 3 tumor it may represent a particularly valid alternative to radical excision. For Beahrs [1] in elderly, frail, poor risk patients, the theoretical advantages of radical surgery may be offset by the mortality and morbidity of the procedure. He emphasized that in such cases the clinician should leave his options open. For Goligher [10] in elderly patients especially those in poor social conditions or living alone, a permanent colostomy may become a major problem, which may produce profound psychological upset. In the framework of those patients having a short expectation of life, it is rational to try to avoid a permanent colostomy. If one takes into consideration all these data, one must conclude that radiotherapy has a major role to play in the management of cancer of the rectum, in association with surgery or alone. This goal can only be achieved if several conditions are met: (1)The protocol of irradiation must be well adapted to the final purpose. (2)The radiation oncologist must be fully aware of the responsibility he is taking especially when the treatment aims at controlling the tumor by irradiation alone. His responsibility concerns not only the definition of the protocol of treatment, but also the technical details of its daily application and the follow-up of the patient. (3) This strategy may only be conceived as a teamwork. That implies a perfect un-
282
derstanding and a climate of confidence between radiation therapists and surgeons. The radiotherapist must be conscious of the limits of this method and keep in mind that surgery remains the conventional modality of treatment of rectal cancer, and that salvage surgery may be used in case of local failures. When these conditions are met the optimal chances are given to each individual patient not only to be cured but also to have a good quality of life after treatment.
References 1 Beahrs, O.H. Status of fulguration and cryosurgery in the management of colonic and rectal cancer and polyps. Cancer 34: 965-968, 1974. 2 Beynon, J., McMortensen, N. J., Foy, D. M. A., Channer, J. L., Virsee, J. and Goddard, P. Endorectal sonography: laboratory and clinical experience in Bristol. Int. J. Colorectal. Dis. I: 213-215, 1986. 3 Biggers, O. R., Beart, R. W, Jr. and Ilstrup, D.M. Local excision of rectal cancer. Dis. Colon Rectum 29: 374-377, 1986. 4 Boulis-Wassif, S., Gerard, A., Loygue, J., Camelot, D., Buyse, M. and Duez, N. Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-Fluorouracil, followed by radical surgery. EORTC trial. Cancer 53: 1811-1818, 1948. 5 Bugat, R., Nguyen, T.D., Naja, A. and Combes, P.F. Les r~cidives pelviennes du cancer du rectum apr6s chirurgie d'amputation. A propos d'une s6rie de 52 observations. Semin. Hop. Paris 56: 1779-1786, 1980. 6 Crile, G. and Turnbull, R.B. The role of electrocoagulation in the treatment of carcinoma of the rectum. Surg. Gynecol. Obstet. 135: 391-396, 1972. 7 Culp, C.E. Conservative management of certain selected cancers of the lower rectum. In: Controversy in Surgery, pp. 404-414. Saunders, Philadelphia, 1976. 8 Cummings, B.J. A critical review of adjuvant preoperative radiation therapy for adenocarcinoma of the rectum. Br. J. Surg. 73: 332-338, 1986. 9 Deucher, F. and Nothiger, F. Der transanal Eingriff beim Rectumcarcinom. Der Chirurg. 49: 260-264, 1978. 10 Goligher, J.C. Treatment of carcinoma of the rectum In: Surgery of the Anus, Rectum and Colon, 3rd edn., pp. 639-813. Charles C. Thomas, Leeds, 1977. 11 Hawley, P. R. and Ritchie, J.K. Indication technique and results oftransanal tumour excision in cases of lower rectal carcinoma. In: Der Mastdarmkrebs, pp. 46-48.
Editors: H. Reifferscheid and S. Langer. Thieme, Stuttgart, 1980. 12 Hermanek, P., Altendorf, A. and Gunselmann, W. Pathomorphologische Aspekte zu kontinenzerhaltenden Therapieverfahren bei Mastdarmkrebs. In: Der Mastdarmkrebs, pp. 1-12. Editors: H. Reifferscheid and S. Langer. Thieme, Stuttgart, 1980. 13 Jackman, R.J. Conservative management of selected patients with carcinoma of the rectum. Dis. Colon Rectum 4: 42, 1961. 14 Kovalic, J.J. Endocavitary irradiation for rectal cancer and villous adenomas. Int. J. Radiat. Oncol. Biol. Phys. 14: 261-264, 1988. 15 Lamarque, P. L. and Gros, C.G. La radioth6rapie de contact des cancers du rectum. J. Radiol. Electrol. 27: 333-348, 1946. 16 Lasser, P., Lacour, J. and Gadenne, C. The place of electrocoagulation in treatment of cancer of the rectum. J. Exp. Clin. Cancer Res. 4: 427-429, 1983. 17 Lavery, I. C., Jones, I. T., Weakley, F. L., Saxton, J. P., Fazio, V.W. and Jagelman, D.G. Definitive management of rectal cancer by contact (endocavitary) irradiation. Dis. Colon Rectum 30: 835-838, 1987. 18 Lazorthes, F., Fages, P., Chiotasso, P. and Bugat, R. Synchronous abdomino-trans-sphincteric resection of low rectal cancer: new technique for direct colo-anal anastomosis. Br. J. Surg. 73: 573-575, 1986. 19 Madden, J.L. L'61ectrocoagulation dans le traitement du cancer du rectum. Chirurgie 105: 15-24, 1979. 20 Morson, B. C. and Bussey, H. J.R. Surgical pathology of rectal cancer in relation to adjuvant radiotherapy. Br. J. Radiol. 40: 161-165, 1967. 21 Myerson, R.J., Walz, B.J., Kodner, I.J. and Fry, R. Endocavitary radiation for early rectal carcinomas: the experience at Washington University. Int. J. Radiat. Oncol. Biol. Phys. 13, Suppl. I: 194, 1987. 22 Nicholls, R. J., Galloway, D. J,, Mason, A. Y. and Boyle, P. Clinical local staging of rectal cancer. Br. J. Surg. 72: 51-52, 1985. 23 Papillon, J. Rectal and anal cancers. Conservative treatment by irradiation: an alternative to radical surgery. Springer Ed., New York, 1982. 24 Papillon, J. The future of external beam irradiation as initial treatment of rectal cancer. Br. J. Surg. 74: 449-454, 1987. 25 Papillon, J. New prospects in the conservative treatment of rectal cancer. Dis. Colon Rectum 27: 695-700, 1984. 26 Rider, W.D., Palmer, J.A., Mahoney, L.J. and Robertson, C.T. Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial. Can. J. Surg. 20: 335-358, 1977. 27 Roe, J.P., Kodner, I.J., Walz, B. and Fry, R.D. Preoperative radiation therapy for rectal carcinoma. Dis. Colon Rectum 25: 471-473, 1982.
283 28 Salvati, E.P., Rubin, R.J., Eisenstat, T.E., Siemons, G. O. and Mangione, J.S. Electrocoagulation of selected carcinoma of the rectum. Surg. Gynecol. Obstet. 166: 393-396, 1988. 29 Sischy, B., Hinson, E. J. and Wilkinson, D.R. Definitive radiation therapy for selected cancers of the rectum. Br. J. Surg. 75: 901-903, 1988. 30 Stearns, M.W., Sternberg, S.S. and DeCosse, J.J. Treatment alternatives. Localized rectal cancer. Cancer 54: 2691-2694, 1988. 31 Stevens, K.R., Jr., Allen, C.V. and Fletcher, W.S. Preoperative radiotherapy for adenocarcinoma of the rectosigmoid. Cancer 37: 2866-2874, 1976. 32 Turnbull, R. B., Jr. Carcinoma of the rectum: nonresecrive treatment. Dis. Colon Rectum 17: 588-590, 1974.
33 Wang, C. C. and Schulz, M.D. The role of radiation therapy in the management of carcinoma of the sigmoid, rectosigmoid and rectum. Radiology 79: 1-5, 1962. 34 Whiteway, J., Nicholls, R. J. and Morson, B. C. The role of surgical local excision in the treatment of rectal cancer. Br. J. Surg. 72: 694-697, 1985. 35 Williams, I. G. and Horwitz, H. The primary treatment of adenocarcinoma of the rectum by high voltage roentgen-rays (1000kV). Am. J. Roentgenol. 76: 918-928, 1956. 36 York Mason, A. Rectal cancer: the spectrum of selective surgery. Proc. R. Soc. Med. 69: 237-244, 1976.
Elsevier
275
RADION00673
Present status of radiation therapy in the conservative management of rectal cancer J. Papillon Centre L~on B~rard, Lyon, France (Received 3 January 1989, revision received 9 May 1989, accepted 2 October 1989)
Key words: Rectal cancer; Conservation; Radiotherapy
Summary Conservative treatment of rectal cancer may be a valid alternative to radical surgery in cases selected with regard to their very low probability of lymphatic spread. Beside the surgical modalities of local treatment, radiation therapy has gained a substantial place thanks to the use of intracavitary irradiation (contact X-ray therapy and interstitial curietherapy). In a series of 310 cases of T1-T 2 tumors followed more than 5 years, the rate of death of cancer is 7.7 ~o and the rate of local failures is 5 ~o, significantly inferior to that following local excision or electrocoagulation. Moreover, in elderly poor risk patients with T2 or T 3 tumors of the lower third of the rectum, it is possible to extend somewhat the field of conservative treatment without jeopardizing their chance of cure. The protocol is based on a short but intensive course of external beam irradiation (30 Gy over 12 days) followed 2 months later by intracavitary irradiation directed to the tumor bed. The purpose of this strategy is a tentative conversion of low-lying tumors suitable for abdominoperineal resection into lesions amenable to conservation. In a series of 71 patients (mean age 74 years) with selected T 2 or T 3 tumors larger than 4 cm, followed more than 3 years, the rate of death of cancer is 11~o and the rate of death of intercurrent disease is 22~o. At 5 years the rate of death of cancer is 16 ~o. It is emphasized the necessity of a strict selection of cases by clinical means and endorectal sonography. This strategy must only be conceived as a teamwork of radiation therapists and surgeons.
Introduction Conservative treatment of rectal cancer has long been considered as a dangerous heresy. Most Address for correspondence: J. Papillon, Centre Lron Brrard, 28 Rue La~nnec, 69008 Lyon, France.
surgeons were reluctant to perform limited operations, fearing that such procedures might not be curative and rightly regarding cure as more important than the avoidance of a colostomy. During the past decade there has been significant changes of opinion and, although major surgery remains the conventional approach to rectal
0167-8140/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)
276 cancer, conservative procedures have gained a place in the management of low-lying tumors as an alternative to radical surgery. These changes are due to progress in the knowledge of the clinical behavior of the tumor, of the prognostic value of histological grading and of the relationship between local and regional spread. Local treatment should only be considered if the long-term results are at least equal to those of major surgery. That implies that rectal cancers submitted to conservative treatment should be a local disease with a very low probability of lymphatic involvement. This rule is the key factor of the case selection. Irrespective of the method used, the selection is based on several criteria: (1) Histological grading based on multiple biopsies. Only well- and moderately well-differentiated adenocarcinomas may be accepted. (2) Local spread. Morson and Bussey [20] have shown that until penetration of the rectal wall has taken place the chance of lymphatic metastases having already occurred is very low in the range of 6~o. They estimated that these lesions may be considered with a high probability as a local disease and submitted to a local treatment. This statement, which has been confirmed by Hermanek [12] and Turnbull [32], indicates that T1 and some T 2 tumors may be treated locally. Can one stage a cancer accurately before treatment? Up to the last few years the clinician was considered to be unable to have a clear idea of the extent of a tumor. Contrarily, York Mason [36] and Nicholls et al. [22] comparing clinical and pathological data have demonstrated that the clinician, as long as the examination is made carefully, can assess the local spread of a palpable tumor quite accurately. He bases his findings not only on the mobility, which is the most important sign of penetration of the bowel but also on the configuration of the growth, its consistency and its histological grading. Endorectal sonography has improved this preoperative clinical staging significantly [2]. Compared to the data drawn from operative
specimens, endorectal sonography has an overall correlation coefficient of 90~o. This method can predict invasion beyond the muscularis propria with a sensitivity and specificity of about 95 ~o. It is capable of differentiating between inflammatory and malignant infiltration. This brings a new objectivity to an area previously hampered by the subjectivity of digital examination. Endorectal sonography has also the advantage to explore tumors which are not within reach of the examining finger and discover pararectal lymph nodes. By the visualization of all layers of the rectal wall it allows the precise allocation of tumors into the U.I.C.C. groups T1-T4. This method is especially useful in the selection of early T1-T2 invasive, non-pedunculated tumors which can be suitable for conservation treatment. This role of endorectal sonography is so important that local treatment should be undertaken according to the findings of this investigation. (3) Tumor size. Almost all investigators consider that the tumor should not be more than 4 cm in diameter. (4) Accessibility. Most if not all tumors submitted to local treatment may be palpated and are situated in the low- or mid-rectum and easily accessible by transanal approach. (5) Absence of detectable perirectal metastatic lymph nodes. Careful palpation preferably with the patient in the knee-chest position and endorectal sonography are valid means in this systematic search. Pretreatment evaluation must include CT scan of the abdomen and pelvis, CEA level, colonoscopy or double contrast barium enema and general examination to make sure that there is neither distant metastasis nor synchronous colonic carcinoma. Lastly, when a conservative modality has been used it is essential that the patient be followed up closely. The patient must understand the necessity of regular follow-up examinations. If persistence or recurrence of the tumor is discovered in its early stages the radical surgery can be carried out with success in many cases.
277 Material and methods Two modalities of radiotherapy may be used to control rectal tumors.
(1) Intracavitary irradiation Under this heading one must include the contact X-ray therapy with the 50 kV Philips machine and the interstitial curietherapy with iridium-192. These methods represent the most known techniques of local therapy by irradiation [24,25]. Contact X-ray therapy, which is the basic method always used first, is an ambulatory treatment carried out in the out-patient department. It consists of four applications within 6 weeks. During the treatment the radiotherapist wears a leaded rubber apron and a leaded rubber left glove. The X-ray tube is held by its handgrip in his right hand and is fitted in the treatment applicator, which is firmly held by his left hand. The very short time of the application (less than 2 min) and the practical tube construction allows the radiotherapist to "shoot" this radiation as would a pistol. Between each application there is an inter-
val of 1-3 weeks. Usually the treatments take place on days 1, 8, 22 and 43. The overall dose delivered is 100-120 Gy. High doses (20-30 Gy) of low voltage irradiation given at every treatment produce a rapid shrinkage of the exophytic part of the tumor. Hence at the second application, the tumor has usually a greatly reduced volume compared with its initial size. The same process is noticed at subsequent applications, the tumor being destroyed layer by layer. Iridium-192 implant is a supplementary modality, which aims at delivering a booster dose of 20 Gy in 24 h to the tumor bed. The implantation of an iridium fork with two prongs 4 cm long and 16 mm apart is performed under local anesthesia and takes place 4 - 6 weeks after completion of contact X-ray therapy. The experience of the Centre L6on B6rard includes 310 patients treated between 1951 and 1983 with no lost to follow-up. All patients had true invasive well- or moderately well-differentiated sessile adenocarcinoma. Carcinomas in situ, cancers in polyp and degenerated villous tumors were excluded (Tables I and II).
TABLE 1 Intracavitary irradiation of cancer of the rectum contact X-ray therapy + iridium-192: series of the Centre L6on B6rard, Lyon. No. of cases
5-Year survival NED
Death of cancer
Death of intercurrent disease
Postoperative death
310
229 (73.8%)
24 (7.7%)
53 (17%)
4 (0.6%)
TABLE II Pelvic failures after intracavitary irradiation of rectal cancer: series of 310 cases.
No. of cases Local failures Nodal failures
Alive and well
14 (4.5%) 12 (3.8%)
4 3 , ; LI
•i~
'
Death of cancer
Postoperative death
9 8
1 1
278
(2) Combined external beam and intracavitary irradiation in a split-course regimen Intracavitary irradiation, which is applicable to less than 10~o of rectal cancers is not the only means of conservative treatment by irradiation. The purpose of the new protocol, which will be described, aims at extending the field of conservation by irradiation without jeopardizing the chance of cure. The efficacy of external beam irradiation depends on the dose-time relationship and may be evaluated by the study of the operative specimens. Since 1977, a particular modality of preoperative irradiation has been used at the Centre Lron Brrard. It consists of a short but intensive course of irradiation with cobalt-60 using a 120 ° arc rotation through a sacral field. A dose of 30 Gy is delivered in 10 fractions within 12 days. The isodose distribution shows that a hot spot (35 Gy) is given to the tumor area. The main characteristics of the method, which has been previously described [24] are as follows: (1)limited targetvolume, which includes the most important sites of regional spread of rectal cancer; (2)satisfactory protection of the small bowel thanks to the bladder distension. The tolerance is good: proctitis does not last more than 3 weeks and is easily relieved by steroid enemas. The surgical decision was taken after an interval of 2 months. The 2-month rest enlightens the selection process and the downstaging of many tumors may be evaluated according to 127 operative specimens (Table III). These data must be taken into consideration when the clinician is facing a particular problem represented by poor risk patients with T 2 o r T 3 TABLE III Preoperative irradiation and surgery 2 months later: operative specimens. No. of cases
Tumor-free
Dukes' A
Dukes' B
Dukes' C
127
18%
35%
21%
25%
cancers, too large, too infiltrating or too close to the anus to be treated by usual conservative methods. In such cases it is rational to try to convert some tumors of the lower third of the rectum from radical excision into lesions amenable to conservative treatment by using external beam irradiation (30 Gy within 12 days) followed 2 months later by intracavitary irradiation - one application of contact X-ray therapy (25 Gy) and an iridium-192 implant (20-30 Gy). This splitcourse irradiation is only applicable in T 2 or some T 3 tumors selected with regard to histological grading (I or II) and local spread assessed by clinical means and endorectal sonography, which must show no or slight extrarectal spread and no detectable pelvic metastatic nodes. The last but not the least condition is the substantial shrinkage of the tumor at the end of the second month leaving a limited and superficial residual disease suitable for local therapy. This protocol has been applied between 1977 and 1984 to 71 patients (median age 74 years).
Results
Two groups of patients will be studied according to the treatment modality used.
(1) Intracavitary irradiation In the series of 310 patients followed for more than 5 years, immediate tolerance was always good. When the irradiation treatment is finished, most patients do not have any local reaction. Some have a slight proctitis which does not last more than 3 weeks. Superficial radionecrosis is rare (5~o), most of them are asymptomatic and heal spontaneously. Usually follow-up reveals some atrophy of the mucosa. Intracavitary irradiation never gives rise to stricture or narrowing of the rectal lumen, which keeps its normal size and consistency making digital examination particularly easy at subsequent visits. During the follow-up period, occasional bleeding may alarm patients. These episodes due to telangiectasia
279 may require the use of laser applications. Out of the 229 patients alive and well more than 5 years after treatment, 221 have a normal anal function and 8 have a permanent colostomy. The rate of death of cancer is 7.7~o and of intercurrent disease 17~o (Table I). Distant metastases without pelvic disease were observed in seven cases (2 ~ ) . Local failures were seen in 14 patients (4.5 ~o), 9 underwent a radical excision, of them four have been saved and one died postoperatively. Among the 12 patients who developed pelvic metastatic lymph nodes (3.8 ~o) 10 were operated on, of them three have been saved by surgery, either APR (one case) or perirectal lymphadenectomy wihout bowel resection (two cases) (Table II). In the whole group of 26 patients with local or nodal failures, seven were not operated upon because of their poor general condition and/or of the extent of the disease, which was considered to be unresectable. It must be added that five patients with presumed local failure underwent an APR, the operative specimen being tumor-free. Two of them died postoperatively, three are alive and well. The high rate of death of intercurrent disease and the high proportion of postoperative death 4 out of 23 patients operated (17~o) - are the proof that many patients submitted to intracavitary irradiation were poor risk and elderly with a short expectation of life. In the whole series, twothird of patients had polypoid, protuberant tumors, and one third had ulcerative lesions. Among the patients who died of cancer, 11 (45 ~o) had an ulcerative tumor. In the interpretation of these figures it must be taken into consideration that this series dates from a period when endorec-
tal sonography was not available and that some of the cases treated were borderline indications of intracavitary irradiation alone and should have required a different strategy such as the combined irradiation. (2) Combined external beam and intracavitary irradiation Seventy-one elderly poor risk patients with T z or T 3 well- or moderately well-differentiated adenocarcinoma of the lower third of the rectum underwent a combined irradiation. The tumors were considered not suitable for intracavitary irradiation because of their size, their degree of infiltration or penetration of the rectal wall or their location in the juxta-anal area. The minimum follow-up is 3 years. Forty-six (64.7~o) are alive and well, 44 of them with a normal anal function, two with permanent colostomy for local failure. Among the 8 patients who died of cancer, 3 had distant metastasis, 5 died of pelvic failure. One 84-year-old patient died after an APR for local failure. At 5 years the rate of death of cancer is 16 ~o, whereas the death of intercurrent disease is 28 ~o. This figure is due to the poor general condition of most patients. The tolerance of this treatment was generally good. Benign and superficial radionecrosis which healed spontaneously was observed in five cases (Table IV).
Discussion
There are three main methods of conservative treatment: local excision, electrocoagulation and
TABLE IV Tentative conversion of T2, T 3 low-lying tumors from radical excision into conservative treatment in poor risk patients by split-course external beam irradiation and intracavitary irradiation.
At 3 years At 5 years
No. of cases
Alive and well
Death of cancer
Death of intercurrent disease
Postoperative death
71 49
46 (64%) 26 (53%)
8 (11%) 8 (16%)
16 (22%) 14 (28%)
1 1
280 TABLE V Local excision for rectal cancer. Author
No. of cases
Rate of local failures (~o)
Hawley and Ritchie [ 11] Hermanek et al. [12] Deucher and Nothiger [9] Stearns et al. [30] York Mason [36] Biggers et al. [3] Whiteway et al [34]
42 48 34 31 41 141 42
20 10 11 25 7 27 16
irradiation. At St. Mark's Hospital, the percentage of local excisions gradually increased from 1~o in 1948 to 9 ~ in 1975. The principal statistics of local excision are reported on Table V. Electrocoagulation was popularized by Jackman [13] in 1961. The most important series are reported on Table VI. The first treatments by intrarectal contact X-ray therapy with the Philips unit were made by Lamarque [ 15] in Montpellier, France in the 1940s. The development of the method dates from 1951 in Lyon [23,25]. The first applications in the U.S.A. date from 1973 by Sischy [29], who treated 192 cases followed for 1 to 14 years. In this series the rate of local failures is 5 ~o, similar to that of our own series. During the past few years several investigators have published their experience of intrarectal application of the 50 kV Philips machine. Myerson et al. [21] reported on 57 cases followed for 1 to 6 years with 30~o of local failures. Lavery et al.
[17] published 62 cases followed from 2 to 13 years with 18~o of local failures. Kovalic [14] reported on 32 cases followed from 1 to 9 years with 2 4 ~ of local recurrence. The high rates of local failures in the most recent studies compared with the results obtained at the Centre Lron Brrard and by Sischy can only be explained by differences both in case selection and in radiotherapy technique. Dose fractionations also differ markedly from the original technique. Iridium192 implant, which certainly increases the chance of tumor control, is almost never mentioned in the recent series. It is all the more difficult to compare surgical and radiotherapeutic methods of local therapy as there are great differences in the rates of success among the series of local excision (Table V) and among the series of electrocoagulation (Table VI) although the criteria of selection are apparently similar. As far as the radiotherapy is concerned, some points may be emphasized. (1) Cancer of the rectum is radiosensitive enough to be controlled at its early stage by irradiation alone. (2) Intracavitary irradiation properly applied strict selection of early rectal cancer, careful technique - is highly curative with a rate of local failures in the range of 5~o, significantly lower than those reported in most statistics of local excision or electrocoagulation. (3) Contact X-ray therapy has a progressive and selective action. Irradiation has a differential effect related to the degree of radio-sensitivity of
TABLE VI Electrocoagulation for rectal cancer. Author
No. of cases
Rate of local faillures ( ~ )
Crile and Turnbull [6], Turnbull [32] Culp [7] Madden [19] Salvati et al. [28] Lasser et al. [16] Lazorthes et al. [18]
62 67 175 81 20 20
13 25 23 38 5 5
281 neoplastic and normal tissues. The four applications of X-rays are separated by interval of 1-3 weeks. During this period, the response of the tumor to treatment is used as a guide to identify the appropriate target-volume and the dose to be delivered. The progressive action is the key factor of success of the method. (4) Intracavitary irradiation may be applied to tumors of the anterior wall of the rectum in female patients or at the level of peritoneal reflexion without risk of perforation or fistula. (5) The scar after irradiation is supple or slightly fibrotic without any narrowing of the rectal lumen, making follow-up examination particularly easy, whereas the scar after electrocoagulation is often hard and retracted with some degree of stricture formation. (6) The percentage of metastatic lymph nodes observed during the follow-up is in the same range as the probability of lymphatic spread mentioned by Morson and Bussey [20] for T~ and T 2 wellor moderately well-differentiated adenocarcinomas.
At present, intracavitary irradiation is able to control most T~ tumors not larger than 4 cm in diameter. Limited T 2 lesions may also be controlled by intracavitary irradiation, but the experience of the protocol combining external beam and intracavitary irradiation in a split-course regimen urges us in case of ulcerative T 2 carcinomas or of cancers located in the juxta-anal area to apply this modality rather than intracavitary irradiation alone. Many reports devoted to preoperative irradiation have shown that some patients with T 2 o r T 3 tumor have a specimen free of tumor cells, especially when surgery takes place more than 3 weeks after completion of irradiation [4,5,24,25,29,31,33,35]. Theoretically, the 23 patients of our series with tumor-free specimens could have been spared major surgery. Among the 45 patients with Dukes' A specimen, 10 had only microresidual disease which could have been possibly controlled by a local method. These examples indicate that external beam ir-
radiation may be more effective than expected. Wang and Schulz [33] in 1962 were among the first to report cure at 5 years after external beam irradiation alone and considered that 6 of their 58 inoperable patients may have been cured in this way. Rider et al. [26] and Cummings [8] showed that protracted irradiation is able to control mobile tumors in 38~o of cases. They emphasized that the tumor response is particularly slow and that an early decision may be inadequate. In these series external beam irradiation was used alone, whereas in our study the booster dose given by intracavitary irradiation after an interval of 2 months increases substantially the efficacy of radiotherapy. Conservative treatment may be applied to middle-aged patients with early rectal cancer but in patients older than 70 with T 2 or T 3 tumor it may represent a particularly valid alternative to radical excision. For Beahrs [1] in elderly, frail, poor risk patients, the theoretical advantages of radical surgery may be offset by the mortality and morbidity of the procedure. He emphasized that in such cases the clinician should leave his options open. For Goligher [10] in elderly patients especially those in poor social conditions or living alone, a permanent colostomy may become a major problem, which may produce profound psychological upset. In the framework of those patients having a short expectation of life, it is rational to try to avoid a permanent colostomy. If one takes into consideration all these data, one must conclude that radiotherapy has a major role to play in the management of cancer of the rectum, in association with surgery or alone. This goal can only be achieved if several conditions are met: (1)The protocol of irradiation must be well adapted to the final purpose. (2)The radiation oncologist must be fully aware of the responsibility he is taking especially when the treatment aims at controlling the tumor by irradiation alone. His responsibility concerns not only the definition of the protocol of treatment, but also the technical details of its daily application and the follow-up of the patient. (3) This strategy may only be conceived as a teamwork. That implies a perfect un-
282
derstanding and a climate of confidence between radiation therapists and surgeons. The radiotherapist must be conscious of the limits of this method and keep in mind that surgery remains the conventional modality of treatment of rectal cancer, and that salvage surgery may be used in case of local failures. When these conditions are met the optimal chances are given to each individual patient not only to be cured but also to have a good quality of life after treatment.
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