|Ahead of print publication
Type C1 radical hysterectomy in advanced squamous cell carcinoma of the cervix postdefinitive concurrent chemoradiation: An argument
Gouthaman Shanmuga Sundaram1, Snehalatha Kothari2, Sri Karthik Voleti1, Vijay Krishna1, Jagadesh Chandra Bose1
1 Department of Surgical Oncology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
2 Department of Obstetrics and Gynecology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, Tamil Nadu, India
|Date of Submission||01-May-2020|
|Date of Decision||18-Jun-2020|
|Date of Acceptance||10-Sep-2020|
|Date of Web Publication||03-Aug-2021|
Gouthaman Shanmuga Sundaram,
Department of Surgical Oncology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Porur, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Aims: This study aimed to evaluate the feasibility and outcomes of patients with advanced cervical cancer treated with definitive concurrent chemoradiotherapy followed by Type C 1 nerve-sparing radical hysterectomy.
Settings and Design: This is a prospective study to assess the feasibility of Type C 1 nerve-sparing radical hysterectomy postdefinitive chemoradiation in advanced carcinoma cervix.
Subjects and Methods: We analyzed 25 patients with cervical cancer evaluated and treated with concurrent chemoradiation followed by surgery. Twenty patients underwent Type C 1 nerve-sparing radical hysterectomy by open surgery and five patients by laparoscopic approach. Postoperative morbidity and pathology were analyzed.
Statistical Analysis Used: Analysis of the outcomes was done by arithmetical calculations.
Results: Eight patients (32%) had persistent residual disease after definitive chemoradiation followed by surgery. Rest of the patients had pathological complete response. Two patients (8%) had node-positive disease. None of the patients in the laparoscopic group had bladder morbidity. One patient in the laparoscopic group had persistent vaginal discharge.
Conclusions: Type C1 nerve-sparing radical hysterectomy is technically feasible with minimal morbidity following definitive chemoradiation in advanced squamous cell carcinoma of the cervix.
Keywords: Cervical cancer, concurrent chemo radiotherapy, type C1 radical hysterectomy
|How to cite this URL:|
Sundaram GS, Kothari S, Voleti SK, Krishna V, Bose JC. Type C1 radical hysterectomy in advanced squamous cell carcinoma of the cervix postdefinitive concurrent chemoradiation: An argument. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 6]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=322908
| > Introduction|| |
Cervical cancer is the fourth leading cause of cancer death in women worldwide, and it is the third most commonly diagnosed cancer. Cervical cancer attributes to around 11% of the total cancer death in women. Sixty percent of cervical cancer patients are not advised for primary radical surgery because of bulky or advanced disease. The International Federation of Gynecology and Obstetrics (FIGO) recommends definitive concurrent chemo radiotherapy as a standard of care for Stages IB2 to IVA patients. Many patients with a histology of squamous cell carcinoma (SCC) can be effectively treated by Concurrent Chemoradiation (CCRT). Nearly 50% of the patients show residual disease (RD) after CCRT treatment. Local recurrence associated with RD after primary CCRT compromises the survival of the patients. Hence, we planned for a feasibility study of Type C1 radical hysterectomy postdefinitive concurrent chemoradiation in patients with locally advanced SCC of the cervix.
| > Subjects and Methods|| |
We performed Type C1 radical hysterectomy (nerve-sparing radical hysterectomy) in 25 patients having locally advanced SCC of the cervix treated with definitive concurrent chemoradiation, during 2017–2019 at our center. Clinical examination was done and appropriate staging was assigned to all the patients. Baseline investigations were done, and subsequently all the patients underwent magnetic resonance imaging of the whole abdomen and pelvis. All the patients were subjected to cervical biopsy for tissue diagnosis. Cervical biopsy was suggestive of SCC in all the patients. Twenty patients underwent open radical hysterectomy (ORH) and five patients underwent the procedure laparoscopically. In the open group, patients with Stage IIB through IIIC 2 were included. In the laparoscopic group, four patients had Stage IIB and one patient had bulky IB2 disease. All the patients underwent definitive concurrent chemoradiation as per the standard international guidelines. In the open surgery group, patients with clinically no RD or suspicious residue were included. In the laparoscopic group, four patients had no clinical RD, and one patient had minimal RD postdefinitive chemoradiation. After a median period of 6–8 weeks postconcurrent chemoradiation, all the patients underwent Type C1 radical hysterectomy (Querleu–Morrow classification) after giving informed written consent and the process was approved by the institutional multidisciplinary tumor board. Bilateral round ligaments were divided. Paravesical and pararectal spaces were defined [Figure 1]. Bilateral pelvic lymph node dissection was done exposing the external iliac vessels, obturator nerve, and anterior branch of internal iliac vessels traced till urinary bladder as superior vesical artery (obliterated umbilical artery) [Figure 2]. Spaces of Luschka and Okabayashi were created. Bilateral uterine arteries and uterine veins were ligated and divided at the origin from the internal iliac vessels. Uterovesical fold of the peritoneum was divided, and bladder dissection from the vagina was done anteriorly. Bilateral ureters were traced till the bladder base after dividing the bladder pillars, ventral parametrium, deep uterine vein, and uterine branch to ureter. Dorsal parametrium was defined between the rectum and lateral pelvic nerves along mesoureter following the embryological planes. Posteriorly, the rectum was dissected away from the vagina. The pelvic nerves were meticulously dissected and preserved along mesoureter. Dorsal parametrium was divided close to the rectum. Paracolpal tissue was divided. Bilateral infundibulopelvic ligaments were divided at the end to avoid rotation of the uterus during the procedure as the whole procedure was done without a uterine manipulator to avoid tumor spill. Type C1 radical hysterectomy was done with adequate vaginal margins [Figure 3].
|Figure 1: Laparoscopic view showing the paravesical and pararectal spaces and uterine artery clipped at the origin|
Click here to view
|Figure 2: Completed right pelvic lymphnode dissection showing right external iliac vessels and right obturator nerve|
Click here to view
|Figure 3: Completed surgery showing the ureters till bladder base and superior vesical arteries and rectum posteriorly|
Click here to view
| > Results|| |
The mean age of the patients was 55 years (range 34–81 years). Bleeding was the most common symptom. The histology was SCC in all the patients. In the postoperative histopathology, eight patients had RD (32%) out of the 25 patients. Seven patients in the open surgery group and one patient in the laparoscopic group had RD. Six patients (24%) had obvious microscopic RD (range 0.6–4 cm). One (4%) had only scattered tumor cells and another patient (4%) had only lymphovascular space invasion (LVSI). Postoperative histopathology revealed pathologic complete response in rest of the patients (68%). Two patients had lymphovascular invasion (8%). Out of the eight patients with RD, four patients (16%) had Grade II disease and two patients (8%) had Grade III disease. Grade could not be assessed in two patients (8%) with RD for two patients. Regarding the nodal involvement, two patients (8%) had positive nodal involvement. The average lymph nodal yield was 15 lymph nodes (range 4–24 lymph nodes). The average blood was 150 mL in the open surgery group <50 mL in the laparoscopic group. The operative time was 2–3 h for open surgery group and 4–5 h for laparoscopic surgery group. There were no intraoperative bladder or bowel injuries. Postoperative residual urine was significant in some patients in the open surgery group and <40 mL in laparoscopic surgery patients. One patient had persistent serous vaginal discharge for I month in the laparoscopic surgery group (Clavien–Dindo classification Grade I), which settled with conservative management. All the patients are on regular follow-up and disease free till date. The clinicopathological characteristics of the patients are listed in [Table 1].
| > Discussion|| |
Radical surgery is generally accepted as a standard of care for patients with early-stage disease and CCRT for patients with advanced-stage disease. A handful of studies have evaluated the importance of adjuvant extrafascial hysterectomy after chemoradiation for locally advanced cervical cancer having controversial results. One study by Sun et al. showed an improvement in the local disease control in patients with a partial pathologic response and enhanced survival. On the contrary, the study by Motton et al. unveiled higher morbidity after hysterectomy and no significant improvement in survival after surgery. As against the study by Motton et al., none of the patients in our series had major morbidity after Type C1 radical hysterectomy. Survival analysis would be known after adequate follow-up with a bigger sample size in our study.
Most studies have offered adjuvant hysterectomy as an advancement in local control but not an impressive strategy for survival.,, RD is perceived as an important prognostic factor due to its correlation between partial response to CCRT and future local relapse. RD postdefinitive chemoradiation and its impact on the survival propelled us to proceed with an aggressive approach and perform radical hysterectomy by the nerve-sparing approach in our patients. One study showed adjuvant extrafascial hysterectomy after CCRT, improving the survival outcome for patients with locally advanced cervical adenocarcinoma of the cervix compared with the current standard care. In our study, eight patients had pathological RD even after treatment by definitive chemoradiation for locally advanced SCC of the cervix treated with curative intent.
Laparoscopic procedure is encouraging for postradiation hysterectomy because of lower blood loss and accelerated recovery. The significance of laparoscopic surgery in cancer related to gynecology has been accepted by many imminent trials. Laparoscopic radical hysterectomy (LRH) has equivalent survival results with ORH and has no effect on the pattern of recurrence in early-stage adenocarcinoma of the uterine cervix. The surgical results were more affirmative than ORH. Another study showed that LRH can be an appropriate therapeutic procedure for the control of FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. Oncologic and functional results of nerve-sparing laparoscopic radical hysterectomy are equivalent to those of conventional LRH. The role of minimally invasive surgery for performing radical hysterectomy for early cervical cancer needs to be questioned following the results of the recently published laparoscopic approach to cervical cancer randomized controlled trial by Ramirez et al. Minimally invasive radical hysterectomy by laparoscopic or robotic approach correlated with high disease recurrence and reduced overall survival than open abdominal radical hysterectomy among early-stage cervical cancer patients. This study was done on patients with early cervical cancer who underwent upfront surgery. This study did not address the issue of performing minimally invasive surgery postchemoradiation in advanced carcinoma cervix. To date, no studies have addressed the role of radical surgery following definitive chemoradiation for locally advanced SCC cervix by laparoscopic approach. We chose the laparoscopic approach for some patients to expedite the process of recovery postsurgery, especially after chemoradiation. Total LRH is considered effective because of very low blood loss and postoperative morbidity. Patients enduring this surgery can be discharged after an overnight stay in the hospital. Our study included five patients undergoing laparoscopic Type C1 radical hysterectomy postdefinitive chemoradiation in Stage IIB and bulky Stage IB2 disease.
Ferrandina et al. found that, after radiation, tissue fibrosis and vascular impairment had significantly increased the complexity of surgery. Another study emphasized that avoiding radical hysterectomy greatly reduces procedure-related morbidity and postsurgery impairment. In contrast to both these studies, Type C1 radical hysterectomy was feasible with less morbidity and better recovery in the postchemoradiation setting in our patients. Meticulous dissection along avascular embryological tissue planes with proper dissection of the pelvic nerves along the mesoureter greatly reduces the morbidity after radical surgery in a postradiation setting.
Our argument for performing radical hysterectomy postdefinitive concurrent chemoradiation is that, even though the patients attain clinical complete response postdefinitive chemoradiation in locally advanced cervical cancer, the cervix may still be harboring microscopic disease as a harbinger for future recurrences as evidenced by the presence of RD in 32% of our patients. At times, the foci of residual tumor may be missed on routine histopathologic examination in a postradiation setting owing to tissue fibrosis even after meticulous search by the pathologist in the available tissue sections. Two of our patients had only scattered tumor cells and LVSI as the evidence of disease, which could have been missed without multiple representative tissue sections by the pathologist. Future recurrences may not be salvageable especially when the patients are lost to follow-up in the third-world scenario, reducing the survival of these patients. Survival of the patients undergoing total pelvic exenteration for recurrent cervical cancer may not be the same as the patients without recurrence. Five-year survival can be as low as 16.8% if the disease recurrence occurs within first 2 years of primary treatment. Our expectation is to enhance the survival of the patients with locally advanced carcinoma of the cervix by preventing future recurrences. The quality of life would improve as well once the patients are free of future recurrences. Though the approach is radical and out of the current treatment recommendations, Type C1 radical hysterectomy is adopted in our study based on our clinical experience and lack of adequate follow-up in the third-world setting. The potential drawback of our study is the inadequate sample size and lack of long-term follow-up and survival analysis to draw definitive conclusions. Patients in the laparoscopic group had a better postoperative outcome compared to open group, though the numbers are disproportionate in both the groups for head-to-head comparison.
In a randomized controlled trial of neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with Stage IB2, IIA, or IIB squamous cervical cancer, cisplatin-based concomitant chemoradiation resulted in superior disease-free survival compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer. The results on overall survival are awaited. This study does not address the issue of performing radical surgery following definitive chemoradiation as in our series.
An ongoing trial addressing the issue of adding radical surgery to chemoradiation in patients with carcinoma cervix is the ABandoning RAd Hyst in cerviX Cancer trial. This is a multicenter, retrospective, cohort study to determine whether the completion of radical hysterectomy improves oncological outcome in patients with intraoperatively detected lymph node involvement before they are referred for definitive chemoradiation in patients with early stage (pT1a–pT2b) cervical cancer, who did not have positive lymph nodes on preoperative imaging. Again, this study does not address performing radical hysterectomy postchemoradiation. A randomized controlled trial with two arms (radical hysterectomy vs. observation) postdefinitive chemoradiation in advanced carcinoma cervix is needed to advocate radical hysterectomy as a recommendation in this scenario.
| > Conclusions|| |
Type C1 nerve-sparing radical hysterectomy is technically feasible with minimal morbidity following definitive chemoradiation in SCC of the cervix. The adoption of this technique and the benefit of minimally invasive approach in the postchemoradiation setting for need validation by further randomized studies.
We would like to thank the Hospital Ward Technician, Mrs. Saraswathy, for follow-up details of the patients. We would also like to thank the SRIHER management for all the facilities. We extend our sincere gratitude and heartful thanks to Miss. Roshni Saravanan and Prof. Ganesh Venkatraman, Department of Human Genetics, SRIHER, for being the main anchors for the study in critically reviewing the paper and instrumental in the final outcome of this article with great support and guidance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > 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 Gynaecol Obstet 2006;95:S43-103.
Wiebe E, Denny L, Thomas G. Cancer of the cervix uteri. Int J Gynaecol Obstet 2012;119:S100-9.
Sun L, Sheng X, Jiang J, Li X, Liu N, Liu Y, et al
. Surgical morbidity and oncologic results after concurrent chemoradiation therapy for advanced cervical cancer. Int J Gynaecol Obstet 2014;125:111-5.
Motton S, Houvenaeghel G, Delannes M, Querleu D, Soulé-Tholy M, Hoff J, et al
. Results of surgery after concurrent chemoradiotherapy in advanced cervical cancer: Comparison of extended hysterectomy and extrafascial hysterectomy. Int J Gynecol Cancer 2010;20:268-75.
Ota T, Takeshima N, Tabata T, Hasumi K, Takizawa K. Adjuvant hysterectomy for treatment of residual disease in patients with cervical cancer treated with radiation therapy. Br J Cancer 2008;99:1216-20.
Touboul C, Uzan C, Mauguen A, Gouy S, Rey A, Pautier P, et al
. Prognostic factors and morbidities after completion surgery in patients undergoing initial chemoradiation therapy for locally advanced cervical cancer. Oncologist 2010;15:405-15.
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. Oncologist 2012;17:64-71.
Ferrandina G, Legge F, Fagotti A, Fanfani F, Distefano M, Morganti A, et al
. Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: Safety, outcome, and prognostic measures. Gynecol Oncol 2007;107:S127-32.
Yang J, Shen K, Wang J, Yang J, Cao D. Extrafascial hysterectomy after concurrent chemoradiotherapy in locally advanced cervical adenocarcinoma. J Gynecol Oncol 2016;27:e40.
Mettler L, Meinhold-Heerlein I. The value of laparoscopic surgery to stage gynecological cancers: Present and future. Minerva Ginecol 2009;61:319-37.
Park JY, Kim D, Suh DS, Kim JH, Kim YM, Kim YT, et al
. The role of laparoscopic radical hysterectomy in early-stage adenocarcinoma of the uterine cervix. Ann Surg Oncol 2016;23:825-33.
Kong TW, Chang SJ, Lee J, Paek J, Ryu HS. Comparison of laparoscopic versus abdominal radical hysterectomy for FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. Int J Gynecol Cancer 2014;24:280-8.
Puntambekar SP, Lawande A, Puntambekar S, Joshi S, Kumar S, Kenawadekar R. Nerve-sparing radical hysterectomy made easy by laparoscopy. J Minim Invasive Gynecol 2014;21:732.
Ramirez PT, Frumovitz M, Pareja R, Lopez A, Vieira M, Ribeiro R, et al
. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med 2018;379:1895-904.
Ramirez PT, Slomovitz BM, Soliman PT, Coleman RL, Levenback C. Total laparoscopic radical hysterectomy and lymphadenectomy: The M. D. Anderson Cancer Center experience. Gynecol Oncol 2006;102:252-5.
Malzoni M, Spina V, Perniola G, Aleandri V, Mossa B, Iuele T, et al
. Laparoscopic surgery in treatment of stage IIb cervical cancer after neoadjuvant chemotherapy. A case report and review of the literature. Eur J Gynaecol Oncol 2003;24:393-7.
Ma Z, Liu R, Wang X, Huang M, Gao Q, Lu Y, et al
. Spontaneous germline potential of human hepatic cell line in vitro
. Mol Hum Reprod 2013;19:216-26.
Gupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri Chopra S, et al
. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIb squamous cervical cancer: A randomized controlled trial. J Clin Oncol 2018;36:1548-55.
Dostalek L, Runnebaum I, Raspagliesi F, Vergote I, Dusek L, Jarkovsky J, et al
. Oncologic outcome after completing or abandoning (radical) hysterectomy in patients with cervical cancer and intraoperative detection of lymph node positivity; ABRAX (ABandoning RAd hyst in cerviX cancer). Int J Gynecol Cancer 2020;30:261-4.
[Figure 1], [Figure 2], [Figure 3]