Dr. med. Dirk Manski

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Radical Nephrectomy for Renal Cell Carcinoma

Indication for radical nephrectomy:

Radical nephrectomy is the standard of therapy for a large renal cell carcinoma or RCC with cava thrombus.

Relative contraindications for nephrectomy:

Partial nephrectomy should be the preferred treatment for smaller tumors or even in large tumors, if partial nephrectomy is technically possible. This is especially important for patients with impending renal failure: increased serum creatinine, proteinuria, diabetes mellitus, arterial hypertension, bilateral renal cell carcinomas or familial renal cell carcinoma.

Surgical technique of radical nephrectomy:

A variety of surgical techniques are available: laparoscopic nephrectomy, retroperitoneoscopic nephrectomy, open transperitoneal nephrectomy or nephrectomy via a flank incision (Robson et al, 2002).

Laparoscopic and retroperitoneoscopic nephrectomy have a lower morbidity and are oncologically equivalent (Hemal et al, 2007). No significant clinical differences were found between the laparoscopic or retroperitoneoscopic approach (Desai et al, 2005). Laparoscopic nephrectomy has become the method of choice for T1–2 renal tumors, which are not suitable for partial nephrectomy and if the tumor size allows the endoscopic technique (EAU guideline, Ljungberg et al, 2010).

Open nephrectomy via a midline incision, subcostal incision or flank incision is preferred for an advanced local tumor stage, e.g. vein invasion with tumor thrombus, infiltration of neighbouring organs, lymph node enlargement or large tumor diameter. Open surgery is also advisable, if significant intraabdominal adhesions from previous surgery are suspected or if the technical skills of the surgeon are inadequate for laparoscopy.

Treatment of renal cell carcinoma with venous tumor thrombus:

Important for treatment planning is the accurate determination of the cranial extension of the tumor thrombus to enable clamping of the vena cava:

For technical details of the surgical management please see section radical nephrectomy.

Adrenalectomy in the context of tumor nephrectomy:

The need for routine adrenalectomy is hardly seen today. Using blunt and sharp dissection, the adrenal gland is separated from the adipose capsule and left in-situ. The involvement of the adrenal gland (1-3%) is almost never an expression of a continuous tumor growth, but represents often metastasis with a poor prognosis (Han et al, 2003). The probability of correct imaging of adrenal involvement using CT is 97%. If adrenal involvement is suspected, adrenalectomy is performed together with radical nephrectomy.

Regional lymphadenectomy:

Lymphadenectomy is not necessary for T1–2 tumors without suspicious lymph node enlargement, since no survival benefit could be demonstrated in a large EORTC study (Blom et al, 1999 and 2009). Some authors advocate on the basis of retrospective studies a lymphadenectomy if advanced tumors or enlarged lymph nodes are present. Lymphadenectomy is recommended from the crus of the diaphragm to the aortic bifurcation. For left-sided tumors the para-aortic lymph nodes are removed, for right-sided tumors the paracaval lymph nodes are removed, and the interaortocaval lymph nodes should be removed for either side (Capitanio et al, 2011).

Oncological results after nephrectomy:

See table Robson stage and survival for the tumor-specific survival rates depending on the clinical stage. More precise results for the survival probability are possible by considering several risk factors, see stage, size, grade, and necrosis (SSIGN) Score [table Assessing SSIGN Score and Survival and SSIGN Score].

Clinical stage and survival: five-years disease-specific survival rate after radical nephrectomy (Guinan et al, 1995).
Clinical tumor stage Five-years survival rate
Stadium I (limited to the kidney) 75–92 %
Stadium II (limited within the renal fascia) 63–77 %
Stadium III (venous invasion, pN+) 38–47 %
Stadium IV (pT4 or M1) 11–12 %

Stage, Size, Grade, and Necrosis (SSIGN) Score for prognosis after surgical treatment of renal cell carcinoma (Frank u.a., 2002a) (Zigeuner u.a., 2010). See table Survival and SSIGN Score for disease specific survival rate depending on SSIGN-Score.
Risk factor Score
T stage
T1 0
T2 1
T3 2
T4 4
Lymph node stage
pNx oder pN0 0
pN1 oder pN2 2
M0 0
M1 4
Tumor size
<5 cm 0
>5 cm 2
Grade 1–2 0
Grade 3 1
Grade 4 3
Tumor necrosis
Not present 0
present 2

Disease specific survival rate depending on SSIGN-Score (Stage, Size, Grade, and Necrosis) (Frank u.a., 2002a) (Zigeuner u.a., 2010). See table Assessing SSIGN Score to assess SSIGN-Score.
SSIGN-Score 1 year 5 years 10 years
0–2 99% 97% 94%
3–4 98% 90% 78%
5–6 93% 74% 57%
7–9 77% 39% 26%
>10 43% 19% 19%

Adjuvant therapy after nephrectomy:

There is a high risk of disease progression for advanced renal cell carcinoma (pN+, T4 oder G3–4 tumors). The therapeutic options for metastatic renal cell carcinoma are limited. Tumor recurrence depends, among other things, on the function of the immune system and thus can theoretically be influenced by adjuvant therapy.

Adjuvant therapy with checkpoint inhibitors:

Keynote-564 is the first phase III trial to demonstrate improved disease-free survival (HR 0.68) and a trend toward improved overall survival (97\,\% vs 94\,\%) due to adjuvant therapy with pembrolizumab after surgical therapy (Choureiri u.a., 2021). Patients with dedifferentiated tumors (grade 4), T3–4, N+, or after complete metastatic resection were included. Final study results have not yet been published; approval was granted 11/2021 by the FDA and 2/2022 by the EMA. There are clear disadvantages for early adjuvant therapy with pembrolizumab: overtherapy of non-metastatic patients, undertherapy of metastatic patients (no TKI), high costs of more than 100000 Euro/year without a proven survival benefit.

Adjuvant therapy with tyrosine kinase inhibitors:

Several randomized studies examined adjuvant therapy with signal transduction inhibitors in patients at high risk of progression after surgery: ASSURE (sunitinib vs. sorafenib vs. placebo) showed no significant advantages (Haas et al, 2017). PROTECT (pazopanib vs. placebo) improved progression-free survival (HR 0.69), but no difference in overall survival could be demonstrated (Motzer et al, 2017). S-TRAC (sunitinib vs. placebo) was able to demonstrate an improvement in progression-free survival (97 vs. 122 of 615 patients developed metastases), overall survival has not benn published yet (Motzer et al, 2018). Significant side effects with long-term administration of TKI were detected in the adjuvant therapy groups, adjuvant therapy is currently not recommended without inclusion into controlled trials and available signal transduction inhibitors are not approved for adjuvant therapy (Sun et al, 2018).

Follow-up after radical nephrectomy:

There are no firm recommendations for follow-up of renal cell carcinoma. According to the recommendations of the EAU and the German S3 guideline, follow-up examinations should be done depending on the symptoms and the likelihood of metastasis. The probability of metastasis can be assessed using the Stage, Size, Grade, and Necrosis (SSIGN) score (Assessing SSIGN Score and Survival and SSIGN Score).

For low risk patients, follow-up is recommended for 5 years. Clinical examinations, laboratory controls and ultrasound controls are recommended in months 3, 6, 12, 24, 36, 48 and 60. The EAU guideline recommends a CT examination only for symptoms that are typical for recurrence. The German S3 guideline recommends a CT of chest and abdomen after 1, 2 and 4 years.

For patients with moderate and high risk, the recommended duration of follow-up is 9 years. Clinical examinations, laboratory controls and ultrasound controls are recommended in months 3, 6, 12, 24, 36, 48, 60, 84 and 108. CT of chest and abdomen after 1, 2, 3, 4, 5, 7 and 9 years. For patients with high risk, perform additional CT of the chest in months 6 and 18. Bone scintigraphy is indicated for patients with bone pain.

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