|Year : 2019 | Volume
| Issue : 1 | Page : 35-38
Retrospective Observational Study of Surgically Treated Patients of Locally Advanced Cervical Cancer After Primary Chemo Radiation at A Tertiary Care Centre in Bihar
Sangeeta Pankaj1, Anjili Kumari2, Jaya Kumari2, Syed Nazneen2, Anita Kumari2, Simi Kumari2, Vijayanand Choudhary3, Rajesh Kumar Singh4, Shishir Kumar5
1 Additional Professor, Gynecological Oncology, IGIMS, Patna, India
2 S.R., Gynecological Oncology, IGIMS, Patna, India
3 Additional Professor, Pathology, IGIMS, Patna, India
4 Professor, Radiation Oncology, IGIMS, Patna, India
5 Assistant Professor, Biostatics, IGIMS, Patna, India
|Date of Web Publication||20-Nov-2020|
Additional Professor, Gynecological Oncology, IGIMS, Patna
Source of Support: None, Conflict of Interest: None
Background: The standard advocated line of treatment of locally advanced cervical cancer is concurrent chemo radiotherapy. Still, there are some discussions about completion surgery following chemo radiation and their benefits in the survival of patients. This study aims at studying the feasibility of such surgery and to document any significant complications and morbidity due to such surgery.
Methods: 17 patients with cancer of the cervix of stage IIB to IIIB who showed residual disease following concurrent chemo radiation and who consented to the trial were recruited from December 2015 to June 2017. 16 patients underwent laparotomy and type 2 hysterectomy and one patient was found to be inoperable on laparotomy. The operative time, blood loss, intra and post-operative complications and duration of hospital stay were recorded and analyzed.
Results: From December 2015 to June 2017, 16 patients were operated. The median age was 55 years (range, 33-65 years). Histologic finding revealed squamous cell carcinoma in 15 (93.75%) cases and adenocarcinoma in 1 (6.25%) cases. International Federation of Gynecology and Obstetrics stages distribution were as follow: IIB, n = 9 (56.25%); IIIA, n = 1 (6.25%); and IIIB, n = 6 (37.50%). Mean estimated blood loss was 400 mL (range, 250-800 ml),and mean operative time was approximately 102 minutes (range, 85-130 minutes). Hospital stay was in average 12 days (range, 10-21 days). Out of 16 cases 4 patients had wound infection, 2 had paralytic ileus, 3 patients had urinary tract infection and 2 developed bladder atony. Secondary resuturing was required in one patient and one patient developed incisional hernia. The patients are on follow up.
Conclusion: Completion surgery by trained surgeons on properly selected patients in institutional settings can be carried out with minimal morbidity to the patients. The effectiveness of this surgery and survival benefits to the patients’ needs to be investigated in bigger trials.
Keywords: Completion hysterectomy, complications, locally advanced cervical cancer (LACC), morbidities
|How to cite this article:|
Pankaj S, Kumari A, Kumari J, Nazneen S, Kumari A, Kumari S, Choudhary V, Singh RK, Kumar S. Retrospective Observational Study of Surgically Treated Patients of Locally Advanced Cervical Cancer After Primary Chemo Radiation at A Tertiary Care Centre in Bihar. J Indira Gandhi Inst Med Sci 2019;5:35-8
|How to cite this URL:|
Pankaj S, Kumari A, Kumari J, Nazneen S, Kumari A, Kumari S, Choudhary V, Singh RK, Kumar S. Retrospective Observational Study of Surgically Treated Patients of Locally Advanced Cervical Cancer After Primary Chemo Radiation at A Tertiary Care Centre in Bihar. J Indira Gandhi Inst Med Sci [serial online] 2019 [cited 2021 Mar 2];5:35-8. Available from: http://www.jigims.co.in/text.asp?2019/5/1/35/301074
| Introduction:|| |
Cancer has been labeled as a “growing epidemic” by the World Health Organization.
Cancer of the cervix is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in females worldwide. It accounts for 11% of the total female cancer deaths. According to GLOBOCAN 2012 statistics the mortality due to cervical cancer has declined in many developed countries which have organized cervical cancer screening programs. The same has not been documented from developing nations. In 2012, it was documented that about 265,000 women died of the disease with over 87.8% of them living in developing countries. Around 60% of the females with cervical cancer are diagnosed with bulky or advanced disease and are inoperable and receive chemo radiation. A study from Thailand has shown that over 80% of new cases of cervical cancer are found at advanced stages (IB2 or more), and over half of these are stage III to IV.
As the cases of cancer are on the rise several studies about their epidemiology and pathogenesis are being undertaken to help understand and prevent the disease process and newer modalities and regimens of treatments are being tested for their effective treatment. In order to improve local control rate and to decrease the rate of distant failure, some authors have suggested the use of completion surgery after chemo radiotherapy (CRT), to remove potentially chemo and radio resistant foci. This approach, currently debated and some authors have shown encouraging results in terms of local control, with reported 78-90% of overall survival at 5th years.,,
A Recently published study conducted in Morocco on 130 patients who underwent surgery following concurrent chemo radiation has shown the overall survival (OS) at 5 years in no hysterectomy arm was 59.8% and in the surgery arm was 88.9% and the relapse-free survival (RFS) was respectively 73.3% and 88.9%. A significant benefit of completion surgery was seen in OS (p=0.011).
On the other hand studies have been published showing significantly increased morbidity in patients undergoing this modality of treatment. The morbidity of completion surgery reported in one study is as high as 25% patients developing postoperative complications of grade 2 and more according the Dindo et al. classification.
In India there is a paucity of screening and early detection facilities that lead to a majority of women being diagnosed at an advanced stage and the burden of morbidity and mortality due to cancer cervix is high. The role of completion hysterectomy and its benefits and demerits is a debated topic in patients with advanced disease. This study aims at investigating the safety and feasibility of completion surgery and document any significant operative challenges in such cases.
| Materials and Methods:|| |
After receiving permission of the ethical committee the study was started in the department of gynecological oncology at IGIMS, Patna.
Patient with cancer of the cervix stage IIB to IIIB having residual disease after concurrent chemoradiotherapy (CRT) and brachytherapy as evident on gynecological examination(Examination under anesthesia) and computerized tomography(CT Scan) of abdomen and pelvis were selected for the study.
To document difficulties faced during surgery and the post operative complications in patients undergoing completion hysterectomy.
To document morbidities due to completion surgery in the operated patients.
The inclusion criteria were
- Stage IIB to IIIB cervix cancer(according to the FIGO classification).
- Age between 25 to 65 years with risk of recurrence of disease.
- Karnofsky-performance status >70.
- H istopathology of cervix biopsy proving adenocarcinoma, squamous cell carcinoma or adenosquamous subtype.
- Received conventional EBRT (45-50Gy) with concomitant chemotherapy (cisplatin 40 mg/m2 per week).
- Received brachytherapy (15 Gy) following EBRT.
- Residual disease clinical and radiological(CT Scan) 8-10 weeks after brachytherapy.
- No extra pelvic disease on CT/MRI.
| Exclusion Criteria:|| |
- Non epithelial carcinomas.
- Patients medically unfit for surgery.
- Interval between pre-operative CTRT and surgery more than 12 weeks.
| Study Design and Treatment:|| |
This was a experimental prospective study with patients recruited between December 2015 to June 2017. A total of 17 eligible consenting patients were enrolled in the study. Concurrent Chemo Radiotherapy and Brachytherapy
All patients received conventional external beam radiotherapy (EBRT (45-50Gy) with concomitant chemotherapy (cisplatin 40 mg/m2 per week) which was followed by brachytherapy (15 Gy).
Patients were assessed for response to CRT and brachytherapy after 8-10weeks. They underwent gynecological examination and MRI Scan of abdomen and pelvis. Those patients with clinical or radiological residual tumor were excluded from the study.
Patients with complete response were planned for laparotomy within a week or two. Patients underwent type 2 hysterectomy. Lymphadenectomy was optional and carried out in those patients who were found to have enlarged lymph nodes at the time of surgery.
Gynecological examination of these patients was done every 3 months. Complications and morbidities were looked for at each visit. At one year of follow up one patient developed recurrent disease and 15 were disease free.
| Results:|| |
Mean estimated blood loss was 250 mL (range, 150-500 ml), and mean operative time was approximately 102 minutes (range, 85-130 minutes). Hospital stay was in average 12 days (range, 10-21 days). 17 patients were recruited in our study over a period of one and a half years after considering the inclusion and exclusion criteria. The patients were aged 33 to 65 years and median age was 55 years. Squamous cell carcinoma was the most common histopathology 94.11% and of the 17 patients only one case was adenocarcinoma. 10(58.82%) cases were FIGO stage IIB, 1(5.88%) stage IIIA and 6(35.29%) stage IIIB.
Type 2 hysterectomy was performed in all cases. One patient was found inoperable on laparotomy as the ureter was densely adherent to the lower uterine segment of the uterus. On histopathology examination of the surgical specimen residual disease was found in 4 patients. 12(75%) patients had no residual disease. Lymph vascular space invasion was found in 1 patient. All specimens had negative margins. Positive pelvic node was found in 1 patient in others lymph nodes were negative.
The patients were monitored for complications. Out of 16 cases 4 patients had wound infection, two had paralytic ileus, three patients had urinary tract infection and two developed bladder atony. Secondary resuturing was required in one patient and one patient developed incisional hernia.
| Discussion:|| |
Cancer of the cervix is the second most common cancer among women and is the most frequent cause of death from gynecological cancers worldwide. India alone contributes to 23% of the total global cases annually. With an annual 67000 deaths, cervical cancer remains one of the major causes of cancer related mortality in India.9Many authors have documented that most of the patients present in advanced stages. A study from Tata Memorial centre, Mumbai India has recorded that of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and1994 669 (11%) patients were in stage Ib, 284 (5%) were in stage IIa, 1891 (30%) were in stage IIb, 69 (1%) were in stage IIIa, and 3321 (53%) were in stage IIIb.10Staging of the disease is done by clinical examination and according to the FIGO staging system. Early stages can be treated by either surgery or radiotherapy. The western nations treat stages IB2 to III by chemoradiation but in resource poor countries like India where there is limited access to radiotherapy, methods to improve operability of locally advanced stages are explored. The treatment of locally advanced cervical cancer by combination of radiotherapy with surgery or chemotherapy with surgery has been studied by several researchers. There is no uniform consensus regarding utility of these methods. Recurrence after treatment with chemoradiation is a difficult situation to treat and so the use of completion surgery is investigated. We have carried out this study to assess the feasibility of surgery after radiotherapy and the complications of this intervention in stages IIB to IIIB of cancer cervix.
We selected patients with complete response after chemoradiation for surgery as the benefit in these patients have been shown to be greater.
Cochrane review showed that study by Morice included women who had a complete response after chemo radiotherapy. It was noted that women with complete response to treatment before surgery potentially have a better prognosis compared to women with residual disease, therefore the role of adjuvant hysterectomy should be assessed in subgroups with similar prognostic factors.
Of the 16 operated cases in our study 12 patients had residual tumor, 2 had microscopic disease of <1 cm and 1 had disease of >1 cm.
A study from India has found that residual disease at brachytherapy had a significant impact on DFS and OS. Other factors such as age, disease volume, parametrial extension, and vaginal extension did not impact the survivals. Thus despite clinical and radiological complete response there was residual pathology in the specimens. Thus removal of radio and chemo resistant foci might be beneficial and help in at least improving the DFS and provide better local control.
Some authors have investigated the possibility of laparoscopic and robotic methods of completion surgery. Gallotta V et.al.in their study on 58 patients have concluded that total laparoscopic radical surgery is feasible in patients with LACC receiving preoperative CT/RT, providing perioperative outcomes comparable to those registered in early-stage disease.
Out of the 16 operated case 6 developed immediate complications of grade 2 and more. The late complications were Lymphedema in 1 patient, recurrent UTI in 2 patients and 1 patient developed incisional hernia. Complication rates in our study is less compared to other studies and can be attributed to the small sample size.
In a multicenter retrospective study, including 111 patients with LACC, treated by standard CCRT followed by brachytherapy, found that completion surgery does not improve OS but may improve DFS.
Cochrane analysis found insufficient evidence that hysterectomy added to radiation and chemo radiation improved survival, quality of life or adverse events in locally advanced cervical cancer compared with medical treatment alone. The trials analyzed were at moderate or high risk of bias. The overall quality of the evidence was variable across the different comparisons and outcomes and was often downgraded due to concerns over the risk of bias and incomplete reporting of outcomes. This downgrading was mainly based on poor reporting and sparseness of data for some of the comparisons, where results were based on a single trial. The imprecision in single trials may be due to the small sample sizes and few events. The decision to offer adjuvant hysterectomy (simple or radical, by open or laparoscopic procedure, with or without lymphadenectomy) needs to be individualized or performed in the context of a clinical trial.
| Conclusion:|| |
Completion hysterectomy has been investigated by various authors as a modality to reduce the recurrence rate and improve the local control and disease free survival. We have studied the safety and feasibility of this surgery and have documented tolerable post operative complications and morbidity which is contrary to other studies which have shown high morbidity. This low rate can be attributed to the small sample size in our study. Thus such surgery can be undertaken at specialized centers by trained surgeons but larger prospective trials need to be conducted to ascertain the benefit of this modality of treatment in terms of DFS and OS.
| References|| |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Quinn MA, Benedet JL, Odicino F, Maisonneuve P, Beller U, Creasman WT, et al. Carcinoma of the cervix uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J GynaecolObstet 2006;95Suppl 1:S43-103.
Khuhaprema T, Srivatanakul P, Sriplung H, Wiangnon S, Sumitsawan Y, Attasara P. Cancer in Thailand 2001-2003. Bangkok: National Cancer Institute 2010;V:3-76.
Cellini N, Smaniotto D, Scambia G, Luzi S, Balducci M, et al. (2008) Chemoradiation with concomitant boost followed by radical surgery in locally advanced cervical cancer: a dose-escalation study. Am J ClinOncol 31: 280-284.
Ferrandina G, Legge F, Fagotti A, Fanfani F, Distefano M, et al. (2007) Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: safety, outcome, and prognostic measures. GynecolOncol 107: 127-132.
Distefano M, Fagotti A, Ferrandina G, Francesco F, Daniela S, et al.(2005) Preoperative chemoradiotherapy in locally advanced cervical cancer: long-term outcome and complications. GynecolOncol 99: 166-170.
Maghous A, Elmarjany M, Marnouche E, Andaloussi K, Bazine A, et al. (2016) Surgical Resection after Concurrent Chemoradiotherapy for Locally Advanced Cervical Carcinoma. J Oncol Med &Pract 1: 107.
Cyril touboul, Catherine uzan, Audrey mauguen, Sebastiengouy, Annie reyet al. Prognostic Factors and Morbidities After Completion Surgery in Patients Undergoing Initial Chemoradiation Therapy for Locally Advanced Cervical Cancer. The Oncologist 2010;15:405-415.
Nandakumar A, Ramnath T, Chaturvedi M (2009) The magnitude of cancer cervix in India. Indian J Med Res 130: 219-221.
Shrivastava S, Mahantshetty U, Engineer R, Tongaonkar H, Kulkarni J, Dinshaw K. Treatment and outcome in cancer cervix patients treated between 1979 and 1994: A single institutional experience. J Cancer Res Ther. 2013;9:672-9.
Morice P, Rouanet P, Rey A, Romestaing P, Houvenaeghel G, Boulanger JC, et al. Results of the GYNECO 02 study, an FNCLCC phase III trial comparing hysterectomy with no hysterectomy in patients with a (clinical and radiological) complete response after chemoradiation therapy for stage IB2 or II cervical cancer. The Oncologist 2012;17(1):64-71.
Mahantshetty U, Shrivastava S, Kalyani N, Banerjee S, Engineer R, Chopra S. Template-based high-dose-rate interstitial brachytherapy in gynecologic cancers: A single institutional experience. Brachytherapy. 2014;13:337-42.
Gallotta V, Ferrandina G, Chiantera V, Fagotti A, Fanfani F et.al. Laparoscopic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study. J Minim Invasive Gynecol. 2015 Jul-Aug;22(5):877-83.
Lèguevaque P, Motton S, Delannes M, Querleu D, Soulé-Tholy M, et al.(2011) Completion surgery or not after concurrent chemoradiotherapy for locally advanced cervical cancer? Eur J ObstetGynecolReprodBiol 155: 188-192.
Kokka F, Bryant A, Brockbank E, Powell M, OramD. Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. Cochrane Database of Systematic Reviews 2015, Issue 4.
[Table 1], [Table 2], [Table 3]