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Keywords:

  • renal cell carcinoma;
  • local relapse;
  • laparoscopic

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References

What's known on the subject? and What does the study add?

  • Local relapse of renal cell carcinoma following radical nephrectomy is rare, and surgical removal provides the only opportunity for cure. Open surgery has been established as the usual approach for these tumours. It is, however, associated with significant morbidity.
  • Our study describes the largest series of laparoscopic treatment of local relapse of renal cell carcinoma with the longest follow-up. We show that the laparoscopic approach is feasible in expert centres. It provides faster recovery and fewer complications with satisfactory oncological outcomes in selected patients.

Objective

  • To assess the feasibility and oncological outcomes of laparoscopic treatment for local relapse of renal cell carcinoma.

Patients and Methods

  • Nine patients were treated by a pure laparoscopic approach for local recurrence of a renal tumour between 2005 and 2011 by a single surgeon (HB), following an initial open radical nephrectomy for the primary tumour.
  • Clinical and histopathological data were collected prospectively and analysed retrospectively.
  • Seven patients were treated by a transperitoneal approach and two patients had a retroperitoneal approach.

Results

  • Relapse occurred within a mean time of 83 months (7–168) following nephrectomy. Recurrent tumour size varied from 2.5 to 4.5 cm. All surgeries were performed laparoscopically without need for conversion.
  • Mean operative duration was 144 min (40–240), mean estimated blood loss was 430 mL (50–1300) and mean hospital stay was 4.5 days (3–6). Three patients had Clavien grade I intraoperative complications. Late complications were noted in two patients (Clavien I and IIIb).
  • Pathology confirmed clear cell carcinoma in all patients with an absence of sarcomatoid features and negative surgical margins.
  • Three patients had neoadjuvant treatment and two patients had adjuvant treatment. In all, 67% of patients were disease free with a mean follow-up period of 3 years.

Conclusions

  • Surgical removal of isolated local recurrence remains the only possibility of cure in patients with renal cell carcinoma.
  • We demonstrated that the laparoscopic approach is a safe and feasible alternative treatment option for selected cases with low morbidity and satisfactory oncological outcomes.

Abbreviations
LR

local recurrence

BMI

body mass index

ASA

American Society of Anesthesiologists

EBL

estimated blood loss

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References

RCC represents the ninth most common malignancy in Europe. In 2008 there were an estimated 88 400 new cases and 39 300 kidney-cancer-related deaths from RCC. There is a 1.5:1 predominance of new cases diagnosed in men over women, with the peak incidence occurring between 60 and 70 years of age [1]. Overall mortality rates in Europe increased until the early 1990s, with rates generally stabilizing or declining thereafter [1]. In all, 13% of patients present with metastasis at the time of diagnosis [2] and metastasis will usually develop in 20%–30% of patients with an organ-confined neoplasm [3, 4]. The majority of recurrences are disseminated, with fewer than 5% of patients presenting with isolated metastasis and local recurrences (LRs) developing in only 1%–2% of patients after radical nephrectomy [5, 6].

Surgical resection of these LRs yields the best result in terms of 5-year survival compared with immunotherapy, radiation and surveillance [5-7]. Open surgery, however, can carry significant morbidity [4-6, 8, 9] and current advances in laparoscopic techniques can provide a considerable advantage in these cases. There is a paucity of comprehensive reports on the laparoscopic treatment of RCC in the current literature, and to our knowledge we report the largest pure laparoscopic series with the longest follow-up.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References

From 2005 to 2011 13 patients were referred to our department for local relapse of renal tumours, nine of whom were treated with a pure laparoscopic approach performed by a single surgeon (HB). The other four patients were not considered as good candidates for the laparoscopic approach and had open surgery. Data were collected prospectively and a retrospective analysis was performed.

Preoperative data included age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score and Charlson index. Data from the initial radical nephrectomy, which was performed in other centres in eight of the nine patients, were reported when available: primary renal tumour size, location, staging, surgical approach, initial pathology and margin status (Table 1). Size and type of recurrence as well as time from initial surgery were also noted (Table 2).

Table 1. Patients and primary renal tumour characteristics.
Patient123456789Mean
  1. CLR, clear cell carcinoma.

Age55777370496876676767
SexMFMFMMMMM7M/2F
BMI (kg/m2)26.127.922.519.221.2NA22.8262524
ASA23312NA233
Charlson13421NA152
Size (cm)9.3 × 7.867 × 553NANA912.5 
Surgical approachOpenOpenOpenOpenOpenOpenOpenOpenOpen 
Staging (TNM 2010)T2aN0M0TxN0M0T1bN0M0T1bN0M0T1aN1M0TxN0M0TxN0M0T3bN0M0 (renal vein)T3bN0M0 (IVC) 
Pathology, FuhrmanCLR (3)CLRCLR (3)CLR (3)CLR (3)CLRCLRCLR (2)CLR (4) 
MarginNegativeNegativeNegativeNegativeNegativeNegativeNegativeNegativeNegative 
Table 2. Relapse surgery: results, complications and follow-up.
Patient123456789Mean
  1. CLR, clear cell carcinoma; CR, complete remission; DOD, dead of disease; M+, metastasis.

Time to relapse (months)3636481447144168982483
Tumour size (cm)2.82.92.53.34434.543.44
Tumour location

Adrenal

Lymph node

AdrenalRenal fossaAdrenalLymph node

Adrenal

Lymph node

Renal fossa

Liver sixth lobe

Renal fossaRenal fossaLymph node 
Surgical approachLap transLap transLap transLap transLap trans

Lap

trans

Lap retroLap transLap retro 
Operative duration (min)1801505040180240120190144
EBL (mL)550505080130050050430
Hospital stay635444554.5
Pathology (Fuhrman)CLR (2)CLRCLR (2)CLRCLR (3)CLR (3)CLR (1)CLR (2)Necrosis 
Peri-operative complicationsDiaphragmatic injury

Diaphragmatic injury

Bleeding

Diaphragmatic injury 
Postoperative complicationsLymphocele

Pleurisy (thoracoscopy)

Transfusion

    
Clavien gradeI   IIIIb I  
Mean follow-up (months)72653954549396638
Systemic treatmentNone

Temsirolimus/

bevacizumab

NoneSunitinibSunitinib

Interferon/

bevacizumab

NoneNoneSunitinib 
Type Adjuvant AdjuvantNeoadjuvantNeoadjuvant  Neoadjuvant 
Current statusCRDODCRM+M+CRCRCRCR 

Selection criteria for the laparoscopic approach were based on preoperative CT scan imaging: the presence of local relapse (including ipsilateral adrenal), with no adjacent organ involvement and absence of metastasis. Patients having multiple lesions and adhesion or invasion of bowel or major vessels were treated with an open approach. One exception was made with patient 6, who had contiguous involvement with the adrenal gland and hepatic lobe following two renal fossa recurrences (Figs 1-4). All indications were presented and discussed in a multidisciplinary team meeting and informed consent was obtained prior to surgery.

figure

Figure 1. Local relapse of RCC with hepatic 6th lobe involvement.

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figure

Figure 2. Local relapse of RCC with hepatic and adrenal masses.

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figure

Figure 3. Local recurrence of the renal fossa.

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figure

Figure 4. Coronal view of hepatic and adrenal local relapse of RCC in contact with the diaphragm.

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The approach for each patient was individualized based upon particular patient and tumour characteristics. Seven patients had a transperitoneal laparoscopic approach in the modified flank position. Open laparoscopy using Hasson's technique was done through a 10-mm supra-umbilical incision to avoid bowel injury. Two trocars were positioned in the para-rectal plane (10 and 5 mm) and an inguinal 5-mm trocar was added for the assistant. An additional 5-mm epigastric trocar was placed for liver retraction for right-sided tumours. The specimen was removed through the initial incision in an endobag and sent for frozen section analysis to assess the margin status when deemed necessary.

In the two remaining patients the retroperitoneal approach was preferred due to tumour location below the renal pedicle (patients 7 and 9). This approach allows better access to these lesions and avoids dissection of bowel adhesions; however, achieving a good retroperitoneal working space can be challenging.

Operative data included surgical approach, operative duration, bleeding and complications using the Clavien grading system. The final pathology report was studied for histological type, Fuhrman grade, margin status and presence of sarcomatoid features.

Patients had a close follow-up protocol with physical examination, laboratory tests and serial imaging every 3months for the first year and then every 6 months thereafter. Details of systemic treatment or need for subsequent surgery were reported with a mean follow-up of 38 months (3–72).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References

A total of seven men and two women with a mean age of 67 years (49–77) had a laparoscopic removal of clear cell carcinoma relapse. Mean BMI was 24 kg/m2. All patients had initial open radical nephrectomy for clear cell carcinoma with negative margins. Pathological staging ranged from T1a to T3b with one patient having a positive lymph node status N1 (Table 1).

Relapse occurred within a mean time of 83 months (7–168) following nephrectomy and was diagnosed on routine follow-up imaging. None of the patients had disease-related symptoms. Patients who had early relapse (less than 36 months) had positive lymph nodes, T3b disease or Fuhrman grade ≥3 (Tables 1, 2).

Recurrent tumour size varied from 2.5 to 4.5 cm. Mean operation duration was 144 min (40–240), mean estimated blood loss (EBL) was 430 mL (50–1300) and mean hospital stay was 4.5 days (3–6) (Table 2).

None of the cases required conversion to an open procedure. One-third of patients had Clavien grade I intra-operative complications. Late complications were noted in 22% (Clavien I and IIIb). Details are summarized in Table 2.

Pathology confirmed clear cell carcinoma in all patients with absence of sarcomatoid features and negative margins. In the five patients who underwent adrenalectomy, recurrence was exclusive to the adrenal in two. Two other patients had removal of lymph node recurrence, and an atypical partial hepatectomy of the sixth lobe and renal fossa recurrence removal were performed for one patient (Figs 1-4). Two patients had exclusive single renal fossa recurrence, and two patients had lymph node recurrence (Table 2).

One patient had multiple renal fossa recurrences following radical nephrectomy in 1994. The first was in 1998 which was treated in another centre with radiotherapy, the second relapse was treated laparoscopically at our institution in 2008, and a third single relapse occurred in 2011 and was treated with the same approach.

Three patients had systemic treatment (neoadjuvant) prior to surgery, two with sunitinib and the other with interferon and bevacizumab. Adjuvant therapy was administered for two other patients (sunitinib and temsirolimus/bevacizumab).

With a mean follow-up of 3 years, two-thirds of the patients were disease free. Three patients had metastasis treated with sunitinib and one of them subsequently died of his disease 5 years following relapse surgery (Table 3). Patients who had a secondary relapse had an initially shorter mean relapse time after radical nephrectomy than those who were on complete remission (62 months vs 86 months).

Table 3. Comparison of published series of local relapse surgery.
SeriesTechniqueNo.Size (cm)Mean EBL (mL [range])Hospital stay (days)Complications (Clavien)Surgical positive marginsFollow-up (months)Disease-free survivalCancer-specific survival
Current (2012)Lap93.44430 (50–1300)4.5

33% (I)

11% (IIIb)

None38 (6–72)67%89%
Yohannan et al. (2010) [12]Lap45.7187.5 (100–250)2.525% (I)None12 (2–24)75%100%
Bandi et al. (2008) [11]Hand assisted lap54.9175 (25–400)4None20%4320%60%
Bruno et al. (2006) [5]Open11NA680 (100–1200)79% (II)None17 (8.2–103.6)27%62% (at 5 years)
Sandhu et al. (2005) [8]Open16NATransfusion 2.5%10

12.5% (I)

12.5% (IIIb)

43%20 (3–78)31%81%
Göğüş et al. (2003) [9]Open108.5NANA10% (V)10%1770%70%
Schrodter et al. (2002) [4]Open135.91933 (300–3500)8–228% (I)None3738%43%
Itano et al. (2000) [6]Open10NA2800 (200–9700)12

20% (I)

10% (IIIa)

NA3920%70%
Esrig et al. (1992) [10]Open11NANANA36%NA4536% 

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References

LR of RCC is rare; complete surgical removal represents the only possibility for cure for these patients with negative surgical margins having a positive impact on cancer-specific survival [5-7]. Itano et al. [6] compared three groups of patients with LR: surgery was performed in 10 patients, 11 patients had chemotherapy, immunotherapy or radiation and nine patients were under observation. The 5-year survival rate was 51%, 18% and 13% respectively. In another study [5] of 34 patients with LR, 18 had pure LR with no associated metastasis; 11 of those patients had open surgical treatment. The 5-year survival rate was 62%; no patient survived at 5 years in the medical therapy group [5]. However, these results are met with a significant morbidity rate varying from 9% to 25% in the open surgical series [4-6, 8, 9]. Postoperative mortality was also reported and was related to digestive resections and anastomotic complications [9, 10]. Mean EBL varied from 600 to 2800 mL and mean hospital stay from 7 to 12 days [4-6, 8, 9] (Table 3).

The laparoscopic approach for these patients could provide less bleeding, faster recovery and shorter hospitalization. In a series of five patients undergoing hand assisted laparoscopic relapse surgery, mean EBL was 175 mL, mean hospital stay was 4 days and no complications were reported [11]; 20% of these patients were disease free with a mean follow-up of 43 months. Yohannan et al. [12] reported four cases of pure laparoscopic approach; the mean EBL was comparable and hospital stay was 2.5 days. One complication was reported (grade I Clavien). With a mean follow-up of 12 months all patients were alive and 75% were disease free (Table 3).

In our experience, the laparoscopic approach provided benefit in these patients with a mean EBL of 430 mL and a shorter hospital stay of 4.5 days. One patient presented with a diaphragmatic injury that was repaired laparoscopically. This was later complicated with pleurisy necessitating thoracoscopy (grade IIIb Clavien). In this patient the laparoscopic approach was difficult due to contiguous involvement of the sixth lobe of the liver, and bleeding (grade II Clavien) occurred during the partial hepatectomy. Follow-up CT scan showed a residual parietal tumour, which was not identified during the laparoscopic approach, and secondary open surgery was required. This could be a disadvantage for this technique in multiple local relapses: tumours can be difficult to identify with anatomical modifications and adhesions, while open or hand assisted laparoscopy could allow tactile identification of these tumours.

However, the pure laparoscopic approach with wide excision of surrounding tissue, including the psoas muscle and the diaphragm, allowed negative margins in all patients. Careful manipulation of the tumour is mandatory as well as extraction with an endobag. No port site metastasis occurred. In these cases we performed irrigation with a mixture of sterile water and povidone; exsuflation was done with the trocars in place, and the incisions were then scrubbed with povidone before closure [13].

Case selection was paramount to minimize repeat resections and intra-operative complications. As our series demonstrates, patients with multiple locations are not ideal candidates for this approach as they present with a higher complications rate and may require additional extirpative surgery. Individualizing the laparoscopic approach was also found to be an important factor in our technique; it allowed better access to the tumour and thus satisfactory oncological results. It also led to a faster postoperative recovery time, with shorter hospital stay and less postoperative morbidity.

Oncological outcomes with a mean follow-up of 3 years suggested improved outcomes in terms of a cancer-specific survival of 89% and a disease-free survival of 67%. This may be due to a difference in the Fuhrman grade and the presence of sarcomatoid features in previous series compared with our cohort. Another factor may be due to the tumour size resected at the time of recurrence. The surveillance protocol has also changed in post-nephrectomy patients over the last decade; our protocol was consistent with the European Association of Urology guidelines. This change of protocol may be a reason for the early diagnosis resulting in a smaller tumour size at the time of recurrence. An additional factor is the use of targeted therapies that were not available in the open surgery reports. In fact the efficiency of these treatments in metastatic RCC has been validated [14]; however, their impact in the preoperative setting is difficult to assess due to the small sample size. Up front cytoreduction with targeted therapy is an interesting paradigm that should be explored in conjunction with planned surgical extirpation.

Our observation also showed that the earliest relapse (7 months) occurred in the N+ patient; this young patient developed early metastatic disease, and is still alive at 54 months after multiple resections and sunitinib treatment. Other risk factors for early relapse might be tumour size and pathological stage [15, 16]. Moreover, early relapse could be a predictor of secondary recurrence after local relapse surgery [17]. In fact mean relapse time after nephrectomy was 62 months for secondary relapse patients compared with 86 months for patients in complete remission. Late relapse of up to 14 years can also occur; this provides a rationale for long-term follow-up after radical nephrectomy in RCC [15].

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References

Laparoscopic treatment of local relapse of RCC is a safe and feasible technique but must be attempted by expert surgeons in a setting where multidisciplinary surgical care is readily available. It allows faster recovery with less bleeding and fewer complications than open surgery when performed by experienced laparoscopists. Three-year follow-up provided satisfactory oncological outcomes and survival. The laparoscopic approach is a good alternative to open surgery in carefully selected cases.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusion
  8. Conflict of Interest
  9. References