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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 9  |  Issue : 4  |  Page : 672-679

Treatment and outcome in cancer cervix patients treated between 1979 and 1994: A single institutional experience


1 Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India
2 Gynae-Oncology Services, Tata Memorial Hospital, Mumbai, India
3 Department of Surgical Oncology, Bombay Hospital Institute of Medical Sciences, Mumbai, India

Date of Web Publication11-Feb-2014

Correspondence Address:
Umesh Mahantshetty
Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai - 12
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.126480

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 > Abstract 

Introduction: A retrospective review in patients with carcinoma cervix to evaluate the changes and trends in demographics, evolution of protocols, and outcome analysis over 16 years.
Materials and Methods: This is a retrospective study of 6234 patients with carcinoma of the cervix treated with radical intent between 1979 and 1994. All the work-up, staging investigations, treatment details, radiation protocols, outcomes, and toxicities were noted, compiled, and analyzed.
Results: With a mean age of 46 years (range: 18-90 years; median: 45 years), 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. With a median follow-up of 68 months (57-79 months) for the entire group, there was no significant difference in the outcome of 953 patients with international federation of gynecology and obstetrics (FIGO) Ib-IIa treated after radical surgery, pre-operative radiation therapy (pre-op RT) + Sx or after radical radiation; their disease-free survival (DFS) was 60-62% at 8 years. In our series of 1891 patients with stage IIb and 3321 with stage IIIb, a respective DFS of 56% and 40% was achieved at 8 years.
Conclusion: Over the last two decades, with the acquisition of newer facilities and inception of Joint Clinics, there has been a significant refinement in the treatment protocols and outcome. Improving radiation strategies to improve therapeutic ratio is the key to success.

Keywords: Cancer cervix, international federation of gynecology and obstetrics stage, late sequelae, pre-operative radiation, radical radiation therapy


How to cite this article:
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 Can Res Ther 2013;9:672-9

How to cite this URL:
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 Can Res Ther [serial online] 2013 [cited 2019 Nov 11];9:672-9. Available from: http://www.cancerjournal.net/text.asp?2013/9/4/672/126480


 > Introduction Top


An estimated 470,000 (15-51% of female cancer patients) new cases of cervical cancer are diagnosed each year worldwide and 80% of these occur in developing countries. [1] More than 80% are diagnosed at an advanced stage. [2] At our institution every year, 1200-1300 new cervical cancer cases are registered, 500-600 patients get treated with radical intent while remaining referred to their home town, other centers, or palliation. During late 1970s and early 1980s, treatment for cervical cancers was evolving in our center. Various treatment approaches including surgery, pre-operative radiation therapy, radical radiation therapy schedules, different brachytherapy schedules, and FIGO staging refinements have been explored. The purpose of the present institutional retrospective review is to evaluate the changes and trends in patient demographics, evolution of protocols, and outcome analysis over the period 1979-1994.


 > Materials and Methods Top


This is a retrospective study of 6234 cervical cancer patients treated with radical intent between 1979 and 1994. All patients were staged according to FIGO staging after physical and pelvic examinations, complete blood profile, chest radiograph, intravenous pyelogram, and later ultrasonography. Sigmoidoscopy and cystoscopy was done if required. At our institution, Gynecology Joint Clinic was initiated in 1979 and all patients were jointly staged by Radiation and Gynecological Oncologists according to the FIGO guidelines.

FIGO Ib-IIa

Surgery

Patients taken up for surgery underwent Wertheim's (Type III hysterectomy) surgery with bilateral pelvic lymph node dissection.

Post-operative radiation

Patients with high risk factors following surgery, namely deep stromal invasion, lympho-vascular emboli, close or positive cut margins, parametrial extension, or metastatic pelvic lymph nodes received post-operative radiation therapy (PORT). PORT included whole pelvis with 45-50 Gray (Gy) at 2 Gy/fraction (fxn) followed by vaginal cuff brachytherapy 20-30 Gy at mucosal surfaces, using Selectron (low dose rate [LDR]/medium dose rate [MDR]).

Pre-operative radiation followed by surgery (pre-op RT + Sx)

These patients received external radiation of 40 Gy/20 fxn for 4 weeks or 30 Gy/10 fxn for 2 weeks for bulky tumors or 20 Gy/5 fxn for 1 week, at the discretion of treating physician. Few patients also received pre-operative brachytherapy alone with LDR using either vaginal surface applicator or standard Fletcher Suit Applicator 30-34 Gy to point A. All underwent surgery within 1-2 weeks of completion of radiation.

Radical radiation therapy

Patients were treated after clinical planning or simulation with 60 Cobalt or 6/10 MV photons to pelvis. The portals included pelvis from L5-S1 to obturator foramen or 2-3 cm inferior to lower vaginal disease and 1.5-2 cm lateral to pelvic brim. Four-field technique was used when separation at mid-pelvis was > 20 cm. Between 1979 and 1987, a combination of external beam 46 Gy/23 fxn followed by intracavitary (Henschke's or Fletcher Suit Applicator) 30-34 Gy to point A (dose rate 175-275 cGy/h) was delivered. Prior to 1983, few patients received prophylactic extended field radiation (50 Gy/32 fxn/1.5 Gy each) to the para-aortic nodal region. From 1988 onwards, external radiation of 40 Gy/20 fxn for 4 weeks with 4-cm wide divergent 5HVL alloy step wedge mid-line block (MLB) was used after initial 20 Gy followed by two insertions of intracavitary brachytherapy with Fletcher Suit Applicator to 60 Gy point A in 2 fxn at 175-250 cGy/h. The first insertion was in 2 nd -3 rd week and 2 nd after completion of external radiation therapy. The different treatment modalities and protocols over different time periods have been detailed in [Table 1].
Table 1: Carcinoma cervix FIGO Ib-IIa: Evolution of radiation therapy protocols

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FIGO IIb

Patients with FIGO stage IIb received pre-op RT + Sx or radical radiation therapy. The pre-op RT delivered was 30 Gy/10 fxn for 2 weeks or 40 Gy/20 fxn for 4 weeks.

The radical radiation therapy regimens used changed with different phase time period. Between 1979 and 1987, 46 Gy/23 fxn for 30 days to whole pelvis plus 1 fxn LDR brachytherapy 30-34 Gy to point A or 50 Gy/25 fxn for 35 days to whole pelvis plus 1 fxn of LDR brachytherapy 25-30 Gy to point A was used. Few patients also received extended field radiation protocol as mentioned earlier. Later, from 1988 onwards with the introduction of MLB, 50 Gy/25 fxn for 35 days to whole pelvis (with MLB after 40 Gy) plus 1 fxn LDR 30-34 Gy to point A or protocol for IB/IIA radical radiation was delivered.

FIGO IIIb

Between 1979 and 1994, various hypo-fractionated radiation schedules were evaluated. All these patients received 1 fxn of LDR brachytherapy 30-34 Gy to point A after completion of external radiation.

Statistical analysis

Statistical analyses were performed using Statistical Programme for Social Sciences (SPSS version 11.5, Chicago, IL, US) software. Descriptive statistics were prepared for frequencies and cross-tabulations. The significance for correlation was done using Chi-square test. Overall survival, disease-free survival (DFS), and pelvic control rates were calculated using the Kaplan and Meier product limit estimation and log rank test for statistical significance. [3] DFS and overall survival were calculated for the time from the date of starting radiation to the earliest date of relapse and the death, respectively.


 > Results Top


Between 1979 and 1994, out of 8369 patients of carcinoma cervix registered, 6234 were evaluable. A total of 1702 patients (20%) were not evaluable due to reasons such as referred outside or did not come for treatment, incomplete treatment, and lost to follow-up further. A total of 433 (0.6%) patients had FIGO stage IVa or too advance disease (frozen pelvis) with poor general condition and received palliative treatment.

Patient demographics

With a mean age of 46 years (18-90 years), 669 (11%) patients had stage Ib, 284 (5%) stage IIa, 1891 (30%) stage IIb, 69 (1%) stage IIIa, and 3321 (53%) patients stage IIIb. Squamous carcinoma was seen in 94%, adeno or adeno-squamous 4% and 2% patients had undifferentiated histology or others. 54.6% tumors were grade III, 16% grade I and in 29.4% grade was not reported or not known. 45.4% of the patients had a bulky (>4 cm) cervical tumor, 43% had moderately bulky (2-4 cm) tumors, and the remainder 8% had small tumors less than 2 cm in size clinically. With a median follow-up of 68 months (57-79 months) for the entire group, further analysis was done according to the FIGO stage and radical treatment received by patients.

FIGO Ib-IIa

Out of 953 patients with FIGO stage Ib/IIa treated, 278 (29%) patients underwent surgery, 283 (30%) Pre-op RT + Sx, and 392 (41%) underwent radical radiation. These treatment modalities were at random decided in the Gynaec Joint Clinic. The patient characteristics are shown in [Table 2].
Table 2: Patient and treatment characteristics of FIGO stage Ib/IIa (953 patients)

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Surgery alone

The immediate surgery-related complications were mild: Six patients (2.5%) with wound infection and burst abdomen, fistulae (recto-vaginal/vesico-vaginal) in five (2%) patients, and post-operative mortality in four (2%) patients. Among patients undergoing Wertheim's surgery, 97 patients (35%) had cervical invasion <1/2, 158 (57%) had >1/2, no invasion noted in 6 (2%), and in 17 (6%) patients the depth of invasion unknown. Similarly, uterine invasion was seen in 54 (17%), vaginal cut margins were positive in 18 (5%) and parametrium positive in 30 patients (10%). The mean number of nodes dissected was 9 (median: 10; range: 5-32 nodes). Seventy-nine (29%) patients had nodes positive with forty-seven (16%) unilateral and twenty-two (8%) had bilateral. A total of 74 patients (27%) underwent PORT, 44 (16%) external alone, 27 (10%) patients external and intracavitary, and 3 (1%) vaginal brachytherapy alone.

With a median follow-up of 49 (mean: 52; 18-132) months, 28 (10.5%) patients had local recurrence, 14 (5.5%) loco-regional, 13 (5%) distant, and 7 (3%) loco-regional and distant metastasis. None of the patients with recurrence were salvaged.

Survivals

The overall DFS was 62% at 8 years. Depth of invasion and pelvic nodal involvement had a significant impact on DFS. Patients with <1/2 cervical invasion had DFS of 80% versus 60% at 8 years with >1/2 cervical invasion (P = 0.01). Similarly, patients with positive nodes had poor outcome with DFS of 50% versus 80% at 8 years for negative nodes (P = 0.002) [Figure 1]. Also, patients who received PORT had a poor outcome with DFS of 50% versus 80% at 8 years for no PORT group (P = 0.0003). This could be because patients who received PORT had nodes positive, suggesting that these were patients with high risk features. Clinical tumor size, however, had no significant impact on the DFS (P = 0.42).
Figure 1: FIGO Ib-IIa disease-free survival with pelvic nodes as a factor

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Pre-op RT + Sx

Out of 283 patients, 75 (26.5%) underwent intracavitary brachytherapy alone and 208 (74%) underwent short course or conventional external radiation. Out of 208 patients, 106 (37.5%) received 30 Gy/10 fxn for 2 weeks, 67 (24%) 20 Gy/5 fxn for 1 week, and 35 (12.5%) patients received 40 Gy/20 fxn for 4 weeks.

Out of 283, 232 (82%) underwent Wertheim's surgery, 26 patients (9%) exploratory laparotomy only (inoperable), and 25 patients (9%) lost to follow-up. Among patients undergoing Wertheim's surgery, 100 (35%) patients had no viable tumor on cervix, 90 (32%) had cervical invasion <1/2 thickness, 83 (30%) >1/2 thickness invasion, and in 10 patients (3%) depth of cervical invasion unknown. Similarly, uterine invasion was seen in 27 patients (11%), vaginal cut margins positive in 5 (1%), and parametrium positive in 16 (6%). The mean number of nodes dissected was 8 (median: 9; 5-29). Twenty-eight (10%) patients had unilateral, while 16 (7%) had bilateral nodes positive.

The immediate surgery-related complications were mild; 15 patients (6%) with wound infection and burst abdomen, fistulae (rectovaginal/vesicovaginal) in 3 (1.2%), post-operative intestinal obstruction in 2 (1%), and post-operative mortality in 4 (2%) patients. A total of 42 patients (15%) underwent PORT, with 26 (9.5%) external alone, 5 (1.5%) intracavitary alone, and 11 (4%) external + intracavitary. With a median follow-up of 48 months (mean: 50 20-129), 42 (15%) had local recurrence, 12 (4.5%) loco-regional recurrence, 8 (3%) distant, 4 (1.5%) loco-regional and distant metastasis, and 16 patients status unknown.

Survivals

The overall DFS was 62% at 8 years. Depth of invasion, tumor size, and nodal involvement had a significant impact on DFS. Patients with <1/2 cervical invasion had better DFS of 75% versus 55% at 8 years with > 1/2 cervical invasion (P = 0.01). Patients with cervical tumor size <2 cm had better DFS compared to 2-4 cm or 4 cm (P = 0.04). Similarly, patients with positive nodes had poor outcome with DFS of 40% versus 78% at 8 years for negative nodes (P = 0.000). There was no significant impact of PORT on DFS (P = 0.31). There was no significant difference in DFS comparing pre-op brachytherapy alone or external radiation (P = 0.09). However, patients receiving shorter regimens of pre-op RT had a better DFS compared to conventional fractionation (P = 0.001) [Figure 2].
Figure 2: FIGO Ib-IIa undergoing pre-operative radiation, disease-free survival with pre-op RT regimens as a factor

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Radical radiation therapy alone

A total of 392 patients underwent radical radiation with 192 (48.5%) patients treated with 46 Gy/23 fxn for 5 weeks plus LDR brachytherapy, 58 (15%) patients extended field radiation protocol, 43 patients (11%) 50 Gy/25 fxn for 5 weeks plus LDR brachytherapy and 101 (25.5%) received 40 Gy/20 fxn for 4 weeks with MLB at 20 Gy +2 fxn LDR intracavitary (30 Gy to point A each). With a mean dose rate of 140 cGy/h, (median: 165; 100-250 cGy/h), 45 (12%) patients received intracavitary with Howard/BARC Applicator, 272 (70%) with Fletcher Suit, 24 (6%) patients with vaginal surface applicator (VSA) and in remaining patients applicator type not documented.

Treatment compliance

A total of 326 (84%) completed the planned radiation, 30 (8%) had incomplete external, 24 (6%) incomplete brachytherapy, and 12 (4%) did not come for radiation. However, all 392 patients were included for the analysis. Acute grade II genito-urinary toxicities was seen in 20 (5%), grade III GI in 4 (1.5%), and grade III moist desquamation in 4 (1%) patients. All toxicities were managed conservatively without any breaks. Similarly, late grade III toxicities reported were 0 rectal in 7 (2%), bladder in 4 (1%), and vaginal fibrosis in 15 (4%) patients. Grade II/III rectal toxicities was only 6% in patients treated with MLB and higher brachytherapy doses, while it was 9% in open pelvic field RT and 15% in patients treated with extended field RT. Similarly, grade II/III bladder toxicities were 2% in patients with MLB, 6% in pelvic field (open) RT, and 8% in extended field RT. With a median follow-up of 35 months (mean: 42 months; 18-153 months), 68 (17%) patients had local recurrence, 21 (5.5%) loco-regional, 7 (2%) distant, 12 (3%) loco-regional and distant metastasis, and in 17 patients status unknown.

Survivals

The overall DFS was 60% at 8 years. Patients with <2 cm cervical tumor had a DFS of 70% versus 50% at 8 years with >4 cm tumor size (P = 0.004). DFS was significantly better with 40 Gy/20 (MLB at 20 Gy) and 2 intracavitary (ICAs) compared to other fractionation schedules treated (P = 0.004) [Figure 3]. To summarize, clinical tumor size had significant bearing on DFS. Radical radiation therapy regimen with MLB and central dose-escalation by brachytherapy results in significantly better outcome both in terms of disease outcome and late toxicities. There was no significant difference in DFS in patients treated with either radical surgery (62%), pre-op RT + Sx (62%) or radical RT alone (60% at 8 years) with P = 0.168 [Figure 4].
Figure 3: FIGO Ib-IIa undergoing radical radiation therapy, disease-free survival with different radiation regimens as a factor

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Figure 4: FIGO Ib-IIa disease-free survival with various treatment modalities as a factor

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FIGO IIb

Out of 1891 patients, 1279 (67.6%) underwent radical radiotherapy, 583 (30.8%) underwent pre-op RT + surgery, and 29 (1.6%) patients underwent surgery alone (not analyzed).

Pre-op RT + Sx

Out of 583 patients, 301 (53%) received pre-operative RT with 30 Gy/10 fxn for 2 weeks, 275 (46.5%) patients 40 Gy/5 fxn for 4 weeks followed by surgery 2 weeks later, and seven patients did not undergo pre-op RT and surgery. Among patients undergoing surgery (n = 576), 354 (60%) patients had no viable tumor, 132 (25%) had cervical invasion <1/2 thickness, and 90 (15%) had >1/2 thickness involved. Similarly, uterine invasion was seen in 21 patients (3.7%), vaginal cut margins positive in 11 (1.9%), and parametrium positive in 20 (3.4%). Lymph node dissection was not done in 187 patients. Out of 396 patients, 75 had positive and 321 negative nodes. With a median follow-up of 45 months (mean: 54; 20-144 months), 68 (17%) had local recurrence, 21 (5.5%) loco-regional, 7 (2%) distant, 12 (3%) loco-regional and distant metastasis, and in 17 status unknown.

Survivals

The overall DFS was 53% at 8 years. Patients undergoing pre-op RT + surgery, depth of invasion, and pelvic nodal involvement had significant impact on DFS. Patients with <1/2 thickness of stromal invasion had a better DFS of 60% versus 40% at 8 years with >1/2 thickness invasion (P = 0.001). Patients with positive nodes had poor outcome with DFS of 20% versus 70% at 8 years for negative (P = 0.000). There was no difference in outcomes in either DFS or OAS for patients receiving different regimens of pre-operative radiotherapy (P = 0.31).

Radical RT

Out of 1,891 stage IIb patients, 1279 received radical radiation therapy with different regimens as shown in [Table 3].
Table 3: Carcinoma cervix FIGO IIb: radical radiation therapy regimens

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Treatment compliance

The acute toxicity profile of patients could not be analyzed due to poor recording and compilation. However, with available data on late toxicities, there was no difference in the incidence of late (grade II and III) rectal and bladder toxicities with different RT treatment regimens, with 3.5% grade II and III rectal and 3% bladder toxicities.

With a median follow-up of 43 months (mean: 43, 6-187 months), 274 (15%) patients had local recurrence, 68 (4%) loco-regional, 55 (3.8%) distant metastases, 30 (2%) loco-regional and distant metastasis, and in 279 (15%) status was unknown.

Survivals

The overall DFS was 56% at 8 years. Patients treated with pelvic radiation with the use of MLB and dose-escalation with brachytherapy had significantly better DFS compared to extended field RT or pelvic (open field) field RT regimens (P = 0.000) [Figure 5].
Figure 5: FIGO IIb undergoing radical radiation therapy. Disease-free survival with different radiation regimens as a factor

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FIGO IIIb

Of 3,321 stage IIIb patients, 3,098 received radical radiotherapy alone and 223 received a combination of radiation therapy and chemotherapy. Various different chemotherapy regimens were used along with radiation like, ifosfamide, bleomycin, cyclophosphamide (C) mitomycin (M) and 5Flurouracil (F) (CMF), etc. Since no further details of chemotherapy (CT) doses, regimens, and CT-related toxicities were available, these patients were combined with RT alone group and analyzed. Various hypo-fractionated RT regimens were randomly delivered as shown in [Table 4]. All these patients received 1# of LDR intracavitary brachytherapy after the completion of external radiation.
Table 4: Carcinoma cervix FIGO IIIb: Different radiation therapy regimens

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Treatment compliance

The available late toxicities were analyzed according to the fractionation schedules used. Grade II and III late rectal toxicities were higher in patients treated with hypo-fractionated regimens as compared to conventional RT regimen (6-9% vs. 4%); similarly, for late bladder toxicities, there was no significant difference (3.5% vs. 3%).

With a median follow-up of 36 (6-126) months, 1059 (31%) had local and loco-regional failure. Forty-seven (1%) had loco-regional and distant failure, and ninety-seven (1.5%) had distant failure alone. In 621 patients (18.5%), the status on follow-up was not known and was taken as recurrence for DFS analysis.

Survivals

The overall DFS was 40% at 8 years. Patients treated with conventional pelvic radiation had significantly better DFS compared with other hypo-fractionated RT regimens (P = 0.000) [Figure 6].
Figure 6: FIGO IIIb undergoing different radiation therapy regimens disease-free survival with different radiation regimens as a factor

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Evolution and outcome with different treatment protocols

Various protocols for each stage group have evolved over a period of 16 years between 1979 and 1994. The period 1979-1983, 1984-1987, and 1988-1994 was time frame for changing protocols, which has been explained in different sections above. We analyzed the disease outcome in relation to these time periods. There is a significant (P = 0.000) improvement in DFS from 35% for 1979-1983 and 45% for 1984-1987 to 55% at 8 years for 1988-1994 not only for the whole group (6234 patients), but also for individual stages [Figure 7]. This significant improvement is also reflected in the change in use of intracavitary brachytherapy applicator system over time from vaginal surface applicator (30% at 8 years) to Howard/BARC applicator (40% at 8 years) and Fletcher Suit Applicator (55% at 8 years) for whole group and individual stages (P = 0.000) [Figure 8].
Figure 7: FIGO Ib-IIIb disease-free survival with different time periods as a factor

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Figure 8: FIGO Ib-IIIb disease-free survival with type of brachytherapy as a factor

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 > Discussion Top


Cervical cancer being a global disease, still remains a major problem in low socio-economic and developing countries with 70-80% diagnosed at advanced stages and poor outcome. [1],[2] At Tata Memorial Hospital, over the past two decades, we have evolved with up-gradation of teletherapy and brachytherapy, in treatment regimens with scientific rationale. In this report, we have tried to introspect our efforts with the intention to refine treatment protocols further. The discussion has been divided according to the FIGO stage and treatment regimens offered in our patients.

Early stage cervical cancers

Radical surgery and adjuvant therapy

In early stage (FIGO stage Ib and IIa) cervical cancers, surgery, irradiation, or combinations have been advocated, each claiming to yield higher cure rates and less morbidity. [4] Although surgery results in accurate staging and appropriate adjuvant therapy, combined surgery and radiation results in increased morbidity. [4] Patients without risk factors have 5-year survival rate of 82-92%. [5] In 1990s, use of adjuvant therapy with stratified risk factors have shown benefit in survivals and is the standard of care today. [6],[7] However, in 1970-1980s, adjuvant therapy was empirical and practiced in patients with high-risk features like pelvic nodal involvement, cut margins positive, etc. In our series of 278 patients treated with surgery, depth of cervical invasion and pelvic nodal involvement significantly affected the DFS irrespective of post-operative pelvic radiation; however, clinical tumor size did not affect the outcome, suggesting that pelvic nodal metastasis is the most important prognostic factor after surgery. Although 27% of these patients underwent PORT by virtue of pelvic nodes involvement, they had poor outcome probably because none received chemoradiation, since the evidence was lacking in those periods. [7] So, the key to success for patients undergoing surgery would be careful selection, low risk of nodal involvement, adequate surgery for primary and pelvic nodes, and judicious use of post-operative adjuvant therapy.

Pre-op RT + Sx

A combination of radiation and surgery has been used to improve therapeutic outcome. Pre-operative radiation (5000-6000 mgh, alone or combined with whole pelvis irradiation) has been administered with a rationale to render tumor biologically non-viable, decrease pelvic and distant relapses. The 5-year survival rate was 89% versus 55% for patients with negative versus positive nodes after pre-op RT, results comparable with our series of 283 patients in which short course hypo-fractionated radiation regimens had better outcome with DFS of 62% at 8 years, 6% incidence of post-operative wound infection, 1.2% intestinal obstruction/fistulae, and 2% mortality. [8] The major criticism of these studies has been conflicting reports of higher rates of complications without significant benefit in outcome. [8],[9],[10] Moreover, this approach is unpopular and seldom practiced today for various reasons such as delay in surgery, probability of disease progression, combining two radical treatments, post-operative complications, surgeon's apprehension of losing patients, and patient's fear of delay in surgery.

Radical radiation therapy

Eifel and associates evaluated 1526 patients with early stage cervical cancer treated with radiation alone and reported DFS of 88% for patients with tumors less than 5 cm, 69% for 5-8 cm, and 47% for >8 cm in diameter. [11] In our series of 392 patients treated with radical radiation therapy, local control rates of 75% and DFS of 60% at 8 years is comparable to the available literature. Also, smaller tumor size and central dose-escalation with brachytherapy significantly improved the outcome. No definite conclusions could be drawn for group (58 patients only) treated with extended field radiation prophylactically.

In our retrospective series, there was no significant difference in outcome in 953 patients treated with surgery, pre-op RT + Sx or radiation with a DFS of 60-62% at 8 years. Although this is not a randomized study, this seems to be a matched control study. Finally, treatment decisions for early stage disease should be based on multiple factors, including age, medical condition, tumor-related factors, and treatment preferences, to yield best cure with minimum complications and the availability of facilities and expertise. These are of utmost importance especially in developing countries.

Advance stage cervical cancers (IIb-IIIb)

Since decades, radiation has played a major role in the treatment of locally advanced cervical cancer. Standard treatment has been radical radiation, with the key to success being administration of appropriate doses to central tumor and pelvic side wall. [12] In different series, 5-year survival rates of 65-75%, 35-50%, and 15-20% have been reported in patients who received radiotherapy alone for stage IIB-IV tumors. [13] Also, the American Brachytherapy Society recommends keeping the total treatment duration to less than 8 weeks because prolongation of total treatment duration can adversely affect local control and survival. [14] Modern approach to the management of cervical cancer has changed to concomitant chemoradiation in advanced cervical cancer with level 1 evidence today with significant improvement in local control and survivals. However, hematological and gastrointestinal toxicities were significantly more with chemoradiation, and no concrete data on late toxicities. [15],[16]

On the contrary, in our series of 1,891 patients with stage IIb and 3321 patients with IIIb treated with radical radiation, a DFS of 56% and 40% at 8 years was achieved. In patients with IIb, central dose-escalation by brachytherapy did improve the outcome (disease and toxicities). Also, in IIIb patients conventional fractionated radiation had better outcome (disease and late sequelae) when compared to hypo-fractionated radiation regimens. In our experience, radiotherapy alone without chemotherapy showed favorable results. Our study showed that survival is not compromised by using radiotherapy alone, provided optimal doses are delivered.


 > Conclusion Top


Over the last two decades, at Tata Memorial Hospital with the acquisition of newer facilities, inception of Joint Clinics (Evaluation by Oncologists of all disciplines together), and evolving radiation strategies, there has been significant refinement in treatment protocols, better patient compliance, and improvement in the outcomes. Multidisciplinary, multimodality approach to each patient is the key to success at our center.

 
 > References Top

1.Stewart BS, Kleihues P. Cancers of female reproductive tract. In: World Cancer Report. Lyon, France: World Health Organization, International Agency for Research in Cancer IARC Press; 2003. p. 215-22.  Back to cited text no. 1
    
2.Dinshaw KA, Rao DN, Ganesh B. Tata Memorial Hospital Cancer Registry Annual Report. Mumbai, India: Department of Biostatistics and Epidemiology, Tata Memorial Hospital; 1999. p. 52.  Back to cited text no. 2
    
3.Kaplan FL, Meier P. Non-parametric estimation from incomplete observations. Am J Stat Assoc 1958;53:457-81.  Back to cited text no. 3
    
4.Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 1997;350:535-40.  Back to cited text no. 4
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5.O′Quinn AG, Fletcher GH, Wharton JT. Guidelines for conservative hysterectomy after irradiation. Gynecol Oncol 1980;9:68-79.  Back to cited text no. 5
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6.Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol 1999;73:177-83.  Back to cited text no. 6
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7.Peters WA III, Liu PY, Barrett RJ II, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606-13.  Back to cited text no. 7
    
8.Gerbaulet AL, Kunkler IH, Kerr GR, Haie C, Michel G, Prade M, et al. Combined radiotherapy and surgery: Local control and complications in early carcinoma of the uterine cervix: The Villejuif experience, 1975-1984. Radiother Oncol 1992;23:66-73.  Back to cited text no. 8
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9.Perez CA, Kao MS. Radiation therapy alone or combined with surgery in the treatment of barrel-shaped carcinoma of the uterine cervix (stages IB, IIA, IIB). Int J Radiat Oncol Biol Phys 1985;11:1903-9.  Back to cited text no. 9
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10.Thoms WW Jr, Eifel PJ, Smith TL, Morris M, Delclos L, Wharton JT, et al. Bulky endocervical carcinoma: A 23-year experience. Int J Radiat Oncol Biol Phys 1992;23:491-9.  Back to cited text no. 10
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11.Eifel PJ, Morris M, Wharton JT, Oswald MJ. The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1994;29:9-16.  Back to cited text no. 11
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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