British Journal of Radiology (2007) 80, e170-e172
© 2007 British Institute of Radiology
doi: 10.1259/bjr/55455027
Neoadjuvant chemotherapy enables R0 resection of locally advanced rectal cancer in a patient with a previously irradiated pelvis
P Sanghera, MRCP, FRCR
1
K Ho, MRCP, FRCR
1
T Muscroft, FRCR
2 and
A Hartley, MRCP, FRCR
1,2
1 Cancer Centre, Queen Elizabeth Hospital, Birmingham B15 2TH, 2 Manor Hospital, Walsall, UK
Correspondence: Dr Paul Sanghera, Cancer Centre, Queen Elizabeth Hospital, Birmingham B15 2TH, UK. E-mail: psangy{at}hotmail.com
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Abstract
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Pre-operative chemoradiation is frequently employed in an attempt to downstage locally advanced rectal cancer which threatens or involves the circumferential resection margin (CRM) on MRI scanning. We present a case where radiotherapy was contraindicated as the patient had previously been irradiated to a radical dose for prostatic adenocarcinoma. Neoadjuvant capecitabine and oxaliplatin were used to downsize the tumour to permit resection with a clear CRM.
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Introduction
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Pre-operative chemoradiation is increasingly the standard treatment for locally advanced rectal carcinoma where the MRI scan suggests that the circumferential margin (CRM) is involved or threatened. Patients presenting in this manner who have received previous radiotherapy to the pelvis for either gynaecological or urological malignancies present a particular problem as further safe irradiation is not possible. The case of a patient previously irradiated for prostate cancer is presented.
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Case
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A 75-year-old male presented with diarrhoea, low abdominal pain and increased flatulence. On rectal examination there was a fixed, ulcerated mass with lower pole 2 cm above the anal sphincter on the posterior aspect of the rectum. A colonoscopy confirmed a large exophytic growth, 2 cm above the anal sphincter, extending to 12 cm and involving more than half the circumference of the rectum. There were no synchronous lesions. Biopsies confirmed invasive, moderately differentiated adenocarcinoma. MRI (Figure 1
) identified a large rectal tumour arising from the right posterior–lateral wall of the rectum, 2 cm above the external sphincter, infiltrating the perirectal fat and mesorectum, with direct extension to the right lateral pelvic wall and levator ani with breech of mesorectal fascia. Some small presacral nodes, not felt to be significant, were also noted. The initial carcinogenic embryonic antigen (CEA) was 25 UG l–1 and prostate specific antigen (PSA) undetectable. Staging CT scan failed to demonstrate any metastatic disease.
The previous medical history consisted of hypertension, prostate cancer and superficial transitional cell carcinoma of the bladder. The prostate cancer was an adenocarcinoma, stage T1c, Gleeson 3+3 with a presenting PSA of 27.8. This had been treated 2 years previously with radical radiotherapy, 55 Gy in 20 fractions using a margin around the prostate of 1.5 cm employing an anterior and two posterior oblique 15 MV beams. The transitional cell carcinoma of the bladder was stage pT1G2 treated with local resection 3 years previously. The patient had subsequently required a further local resection, 15 months later, for a multifocal superficial papillary tumour. Resection was followed by administration of intravesical Mitomycin C.
The case was discussed at the multidisciplinary meeting where the opinion was that the tumour was unlikely to be resected with a clear CRM. Due to prior pelvic irradiation, conventional downstaging long-course chemoradiotherapy was not an option. The symptoms due to the primary tumour were manageable and the patient was offered primary chemotherapy.
The patient completed six cycles of capecitabine and oxaliplatin chemotherapy. He received intravenous oxaliplatin, 85 mg m–2 day 1, and oral capecitabine, 800 mg m–2 days 1–9, repeated every 2 weeks. He tolerated the chemotherapy well, describing grade 1 fatigue but not experiencing any other toxicity. Clinically the primary tumour responded extremely well. After six cycles he underwent repeat MRI scanning and this confirmed a dramatic response (Figure 2). Following repeat discussion at the multidisciplinary meeting the decision was taken to offer him a potentially curative resection. He underwent a low anterior resection, having a colonic J pouch fashioned and anastomosed to the rectal stump, with protective ileostomy. The pathologist confirmed a 16 mm well-to-moderately differentiated adenocarcinoma invading submucosa. The closest distance of tumour to the circumferential margin was 19 mm and 18 lymph nodes were identified, all being free from tumour. Dystrophic calcifications of foamy histiocytes extended through the muscularis into perirectal fat and these changes were thought to represent regressed tumour, downstaging from at least T3 to ypT1. The patient made an unremarkable post-operative recovery. He went on to receive adjuvant single agent capecitabine chemotherapy, at a dose of 1250 mg m–2 for 14 days every 2 weeks, completing four cycles. He remains well and disease free at 9 months following surgery, having undergone reversal of his ileostomy.
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Discussion
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Due to previous radiotherapy for the prostate cancer, the downstaging of this patient's locally advanced rectal cancer in order to render it resectable posed a therapeutic challenge. There is little published evidence on the management of locally advanced unresectable rectal cancers where radiotherapy is not an option. A search of MEDLINE (1966–September 2005) found only one case report describing two patients treated with neoadjuvant irinotecan and 5-fluorouracil (5-FU) prior to surgical resection [1]. However, this clinical presentation may become more common with the increasing detection of prostate cancer in the PSA era. In addition, the increased risk of rectal cancer after prostate cancer irradiation is very small but statistically significant from a review of the SEER database (1973–1993) [2]. The adjusted hazards ratio for development of rectal cancer was 1.7 for the radiation group compared with the surgery-only group (95% CI: 1.4–2.2) [3].
Neoadjuvant chemotherapy has been tested in locally advanced rectal cancer in addition to standard fluoropyrimidine-based chemoradiation in non-previously irradiated patients. In a phase II study of 78 patients capecitabine (2000 mg m–2 day–1 po for 14 days every 3 weeks) and oxaliplatin (130 mg m–2 intravenously every 3 weeks) were given prior to chemoradiation [4]. The radiological response rate to chemotherapy prior to chemoradiation was 81% (2 complete (CR) and 50 partial responses (PR)). These are certainly encouraging data for the use of neoadjuvant chemotherapy in rectal cancer although there was a 5% toxic death rate associated with this schedule. Protracted venous infusional 5-FU (300 mg m–2 day–1 for 12 weeks) and Mitomycin C (7 mg m–2 bolus every 6 weeks) has been used by the same authors in the same setting [5]. Following neoadjuvant chemotherapy the radiological response rate was 27.8% (1 CR and 9 PRs) with 65% having a symptomatic response. Following chemoradiation tumour regression occurred in 80.6% (6 CRs and 23 PRs).
Combination oxaliplatin and infusional 5-FU/LV (FOLFOX) is commonly used in the metastatic setting with objective response rates of up to 54% when used first line [6]. Such a combination of drugs has also been shown to downstage unresectable liver metastases. In one series, 95 out of 701 such patients (13.5%) were rendered operable following chemotherapy. The overall 5-year survival rate in this study was 34% in those patients going on to have a resection [7].
In conclusion, the use of neoadjuvant combination chemotherapy in the patient reported has permitted resection with a clear circumferential margin. Neoadjuvant chemotherapy with capecitabine and oxaliplatin has been shown in one phase II study to have a high radiological and clinical response rate. Response rates with the addition of biological agents such as bevacizumab or cetuximab may be higher. As radiation is associated with long-term morbidity, future trials examining the role of high response rate neoadjuvant chemo/biological regimens compared with combined chemoradiation may appear attractive. However, the risk with such strategies would be the potential for an increase in local failure in the absence of radiation treatment and, in contrast to the use of neoadjuvant radiotherapy, they are not supported by level I evidence. Long-term follow-up of patients in whom radiotherapy is contraindicated and who are therefore treated with chemotherapy alone may help to quantify this risk.
Received for publication January 26, 2006.
Revision received May 5, 2006.
Accepted for publication May 10, 2006.
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References
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- Hasegawa H, Watanabe M, Baba H, Yoshinare K, Mukai M, Kubota T, et al. Neoadjuvant chemotherapy of irinotecan, 5-fluorouracil and leucovorin in patients with advanced rectal cancer. Report of two cases. Hepatogastroenterology 2002;49:891–3.[Medline]
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- Baxter NN Baxter NN, Tepper JE, Durham SB, Rothenberger DA, Virnig BA. Increased risk of rectal cancer after prostate radiation: a population-based study. Gastroenterology 2005;128:819–24.[CrossRef]
- Chau I, Brown G, Cunningham D, Tait D, Wotherspoon A, Norman AR, et al. Neoadjuvant capcitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol 2006;24:668–74.[Abstract/Free Full Text]
- Chau I, Allen M, Cunningham D, Tait D, Brown G, Hill M, et al. Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 2003;88:1017–24.[CrossRef][Medline]
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- Adam R, Avisar E, Ariche A, et al. Five year survival following hepatic resection after neoadjuvant therapy for non resectable colorectal (liver) metastases. Ann Surg Oncol 2001;8:347–53.[Medline]
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Abstract
Introduction
