The profile of Renal Cell CarcinomaatDrSoetomo General Hospital

January 2006 – December 2010

Sriyono1, L. Hakim1,W.D. Soesanto1, S.H. Wijoto1

1Department of Urology, Dr. Soetomo Hospital, Airlangga School of Medicine Surabaya

Abstract

Objectives: To review clinical characteristic of Renal Cell Carcinoma at DrSoetomo General Hospital

Methods: A retrospective study of medical records patients suffering Renal Cell Carcinoma recorded at DrSoetomo General Hospital since January 2006 until December 2010.

Results: There were collected 29 patients, 18 male in majority (62%), with ratio of 1,6:1 to female. The age range was 30-70 years old, mostly 60-70 years old (24%), at mean of 51 years old. Renal tumor classic triad was seen on 9 patients (31%). Major pathological finding was clear cell in 15 (52%) patients, 34% and 10% of papillary and chromophobe, respectively. According to TNM system 2009, the stage presentation T1 was 1(3%) patient,T2a 7(24%), 2b 10(35%), T3a 6(21%) and T4 5(17%) patients. N0 were 21(73%), N1 5(17%) and N2 3(10%) patients. M0 were 23(79%) and M1 6(21%) patients. StageI was 1 (3%) patient,stage II 15(52%), stage III 3(10%)and stage IV 10(34%). Twenty one (72%) patients were, dominantly, underwent nephrectomy,the other 2(7%) underwent partial nephrectomy; 6 (21%) patients underwent palliative nephrectomy and combined withsunitinib in 4 (14%) patients. On three months follow up post operatively, it was found that 2 (7%) patients died and 7 (24%) developed local recurrence tumor.

Conclusion:TheRenal Cell Carcinomain our department; majority were male with ratio 1,6; 1. TheT criteria according to TNM 2009patient camein T1 was 1(3%) patient,T2a 7(24%), 2b 10(35%), T3a 6(21%) and T4 5(17%) patients.Stage of the patient according to 2009 TNM staging systemmost of patient were stage II 15(52%) and stage IV in 10(35%) patient. On short follow up post opoperatively, 2 (7%) patients died and 7 (24%) developed local recurrence tumor.

Keywords: Renal cell carcinoma, clear cell carcinoma, radical nephrectomy

INTRODUCTION

Renal cell carcinoma (RCC)accounts for 2 until 3 % of all malignancies in adults and role as the most lethal of urologic cancers. In USA within 2010, approximately 58.240 new RCCdiagnoses were made, and 13.040 died of RCC. This is primarily a disease of elderly patient of 60 – 70 years old. Men are more often to be affected 1,5 times than women. RCCin childhood is uncommon, about 2.3%-6.6% amongst all renal neoplasms in children. 1,2,3,4.

Kidneys are hidden in the retroperitonealspace which makes renal tumor rarely symptomatic in early stage, until growth as big size tumor. The more radiologic diagnostics are used widely, especially USG, the more coincidental diagnosis are made.4This study’s aim to provide a profile of RCC patients managed in dr. Soetomo hospital, Surabaya, East Java, Indonesia within 5 years, January 2006 until December 2010.

MATERIAL AND METHODS

This is a retrospective study. The samples are all RCC patients who have admitted to Dr. Soetomoacademic hospital within 5 years, from January 2006 to December 2010. Data about gender, age, symtoms, laboratory, stage, histology, treatment and short outcome RCCwere collected form medical record, of Urology department of DrSoetomo hospital.

RESULTS

There were total 29 patients managed within 5 years of 2006 to 2010 in DrSoetomo hospital Surabaya, 18 (62%) were men and 11 (38%) were women.

Table 1. Distribution of renal cell carcinoma based on gender

The mean age is 51 years old, mostly 30-70 years old, at peak of aged 60-70 years old.

Figure 1.Age distribution of renal cell carcinoma

The most frequent symptoms was palpable mass in 25 (86%), followed with flank pain in 17 (59%) and hematuria in 13(45%). Triads of renal tumor waspositive in 9 (31%) patients.

Table 2.Symptoms distribution of renal cell carcinoma

Based on laboratory results, 13(45%) patients had hematuria, 3(10%) had anemia, 4(14%) had leukocytosis and 5(17%) had decrease of renal function test.

Table 3.Laboratory results distribution of renal cell carcinoma

Based on primary tumor, the stage of presentation in T1 was 1(3%) patient, T2a 7(24%), 2b 10(35%), T3a 6(21%) and T4 5(17%) patient.

Figure 2.Primary tumor distribution of renal cell carcinoma

Based on N Staging tumor, the stage of presentation in N0 was 21(73%), N1 5(17%) and N2 3(10%) patients.

Figure 3.N staging tumor distribution of renal cell carcinoma

Based on M staging tumor, the stage of presentation in M0 was 23(79%) and M1 6(21%) patients, where 3(50%) patient metastatik was T4, 2(33%) was T3a and one(13%) patient was T2b.

Figure 4.M staging tumor distribution of renal cell carcinoma

After TNM staging group 2009 were used, most of renal cell carcinoma were stage II 15(52%) and stage IV in 10(35%) and only 1(3%) came in first stage.

Figure 5.Staging distribution of renal cell carcinoma

Based on histologic picture, the most common type is clear cell in 15(52%) followed by papillary in 10 (34%) and chromophobein 2 (7%) patients.

Figure 6.Histology distribution of renal cell carcinoma

Twenty two patients (72 %) were underwent radical nephrectomy, 2 (7%) partial nephrectomy and 6 (21%) palliative nephrectomy followed with Sunitib in 4 (14%) patients.

Figure 7.Surgical treatment distribution of renal cell carcinoma

After three months evaluation, 2 (7%) patients were passed, and 7 (24%) recurrent.

DISCUSSION

Within 5 years of 2006 until 2010 in DrSoetomo hospital Surabaya has been managed patient with RCC, itsappear to be more common in men, 18 (62%) with ratio 6:1 to women, in age of 30 to 70 years old, mostly 60-70 years old (24%) with the average rate 51 years old. Similar to the literature which mentioned men and women ratio of 1,5 : 1, aged 60-70 years old. Our datas similiar to the datas of literatur were to be affected 1,5 times of men, mostlyof 60 – 70 years old. 1,2,3,4.

According to WHO there are subtypes of renal cell carcinoma based on histology which are; clear cell (70% -80%), papillary (10%-15%), chromophobe(3%-5%), collecting duct (<1%), unclassified RCC (1%-3%) and several other rare types such as; multilocular cyst clear cell, medularyrenalis, post-neuroblastoma, mucinous tubular andspindle cell carcinoma. Clear cell and papillary renal cell carcinoma are primarily raised from proximal tubules of the kidney, while chromophobeandcollecting duct are derived from more distal nephron component. Based on genetics, the incidence of RCC also has correlation with familial factors, such as von hippellindau(VHL),hereditary papillary RCC (HPRCC), hereditary leiomyomatosis (HLRCC) and birthogg-dube (BHD).4,5,6

Macroscopically most of RCC are surrounded by a pseudo capsule which is renal parenchyma that is suppressed by the tumor, rarely infiltrative, unlike transitional cell carcinoma, except for collecting duct and sarcomatoidtypes. Clear cell type is yellow-gold colored and has worse prognosis compared to papillary and chromophobe. A papillary type has 2 subtypes; papillary 2is more aggressive and appear to have worse prognosis than type 1. Most patients with collecting ducttype are found in advance stage and have no response to systemic therapy.4,6,7,8

Kidneys are hidden in the retroperitonealwhich makes renal tumors rarely symptomatic, except for big size tumor. The more radiologic diagnostics are used vastly, especially USG, the more coincidental diagnosis are made.4 Three risk factors have close influence to the incidence of RCC, they are tobacco exposure, obesity and hypertension. TNM classification of renal cell carcinoma was made in 2009. Some factors affect the prognosis such as anatomical, histological, clinical, and molecular factors. Anatomical factors are size of the tumor, invasion to the vein, renal capsule, adrenal gland, lymph nodes and also distant metastasis. Clinical factors are performance state, local symptoms, cachexia, anemia and platelet count.9,10,11,12,13.

Table 4.Renal cell carcinoma (RCC) based on 2009 TNM system9

Some of molecular markers like carbonic anhydrase IX (CaIX), vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF), Ki67 (proliferation), p53, PTEN (phosphatase and tensin homolog) (cell cycle), E-cadherin, and CD44 (cell adhesion) have not shown a significance diagnostic value yet.14,15,16.

Based on our data, almost all of the chief complaint were mass 25 (86%) and flank pain 17(59%) while classic triad of renal tumor in 9 (31%) patients because the advance stage of prior presentation. Hematuria was found in 13 (45%) patients of renal cell carcinoma which suggest a suspicion of renal neoplasms besides other urologic cancer.Based on the TNM system 2009,the primary tumor then most of the patients present in T2 (17/58%), T3a in 6(21%), T4 in 5(17%) and only one patient come in T1. Based on N Staging tumor, the stage of presentation in N0 was 21(73%), N1 5(17%) and N2 3(10%) patients. Based on M staging tumor, the stage of presentation in M0 was 23(79%) and M1 6(21%) patients.

In order to see the prognosis, categorizing are done into tumor staging where 15 patients are stage II (52%), 10(34%) are stage IV and only 1(3%) is stage I. This is possible because of community’s lack of awareness of the importance of renal tumor’s early treatment, they don’t come for help when it’s early.

From pathological results, for as many as 15 patients (52%) the most seen type was clear celltype, followed by papillary cellin 10 patients (34%) and 2(10%) werechromophobetype. In accordance with the literature, clear celltype is the majority type of RCC for about 70-80% followed by papillary 10-15% and chromophobe3-5%. We didn’t find any other type at Dr. Soetomo hospital.

Partial resection for local renal cell carcinoma shows a similar outcome to radical nephrectomy. Adrenalectomy is not performed if the adrenal gland is normal on CT or MRI, and found no nodule during surgery without any seen invasion to the upper pole. Lymph node dissection during nephrectomy is proven to give better prognosis and life expectancy, as well as embolization before nephrectomy. For unfit patients who are not possible for surgery, embolization may reduce pain and gross hematuria.16,17,18,19.

Radical nephrectomy is the chosen option for local renal cell carcinoma which is not possible to do partial nephrectomy. Laparoscopy and open surgery have comparable cancer free rates after long period of time, with minimal blood loss and shorter length of stay. Ideal indication for laparoscopy partial nephrectomy is small peripheral tumor. Nephrectomy is curative treatment only as long as all tumors are resectable. In metastatic disease, nephrectomy is palliative, only performed if it is possible. 20,21,22,23,24,25,26

Due to growth of proximal tubule of the kidney, RCC is now showing resistance to some protein drugs, P-glycoprotein and chemotherapy. In metastatic RCC, immunotherapy such as alpha-Interferon (IFN-α) and Interleukin-2 (IL2) show response about 15-20%.Interleukin-2 is more toxic than alpha-IFN and only clear cell type give response to immunotherapy. 27,28,29.

Some targeted therapy which inhibit the vascular endothelial growth factor (VEGF); sunitinib, sorafenib, bevacizumabmaupunpazofenibandmammalian target of rapamycin (mTOR) pathways; temsirolimus and also everolimus, give better outcome than immunotherapy with more tolerable complications. BiphosponatorZoledronicacid are recommended for ones with hyperkalemia with normal kidney function, which are given 4 mg every 4 weeks intravenously. 4,30,31,32,33,34,35

Surveillance is for follow up of possibility of recurrence and metastasis. Recurrence mostly occurs after 3 years of operation, 43% occur in the first year, 70% in the second year, 80% in the third year and 93% in the fifth year. Metastasis is common to the lung, bone, liver, brain and local areas. Local recurrence after nephrectomy occurs in 2.9%, with contralateral recurrence about 1,2% and showing worse prognosis. Surgery is the first choice for local recurrence without distant metastasis. If there is any metastasis, we may give systemic therapy. 36,37,38

Based on our data, 21(72%) patients were performed radical nephrectomy, 2(7%) patients partial nephrectomy, and 6(21%) patients underwent palliative radical nephrectomy, followed with treatment of Sunitibin 4(14%). Radical nephrectomy was performed in almost all patients who were possible for surgery with good performance state, because RCC is radio and chemo resistance, so that there would be no further treatment after surgery. By resecting the kidney along with fascia Gerota and perirenal fat, we expect no metastasis and recurrence.

Two patients were performed partial nephrectomy because the tumors were localized in lower pole of the kidney. While patients who already had metastasis were still underwent palliative nephrectomy. The purpose is reducing huge mass effect, and stops the growth of the primary tumor. Four of them who were performed palliative nephrectomy, were given Sunitib; which is a targeted therapy treatments to inhibit vascular endothelial growth factor (VEGF) then followed further for the hope of better outcome.

Three months of evaluation we found 2(7%) patients were dead and residive in 7(24%) patients. Furthermoreevaluation were difficult because most of the samples live outside Surabaya and might have no complaint which stopped them to come to DrSoetomo hospital. Only 4 patients visited routinely for Sunitib treatment evaluation, but then also discontinue due to drug availability.

CONCLUSION AND SUGGESTION

The Renal Cell Carcinomain our department; majority were male with ratio 1,6; 1. The T criteria according to TNM 2009 patient came in T1 was 1(3%) patient, T2a 7(24%), 2b 10(35%), T3a 6(21%) and T4 5(17%) patients. Stage of the patient according to 2009 TNM staging systemmost of patient were stage II 15(52%) and stage IV in 10(35%) patient. On short follow up post opoperatively, 2 (7%) patients died and 7 (24%) developed local recurrence tumor.

Campaign is needed for general practitioners and radiologist to become aware of renal tumor, so that more RCC will be found at earlier stage. Further study must be done to evaluate side effects and benefits of systemic drug in metastatic renal cell carcinoma, to gain more conclusive advantage of targeted therapy.

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