The peak incidence of RCC occurs between 60 and 70 years of age, with a 3:2 ratio of men to women. Aetiological smoking, obesity and hypertension.
T1a ≤4cm T1b >4-7cm T2a ≤10 cm T2b >10cm
T3a -RV ar iki Gerota riebalus
T3b - VCI
T3c - VCS ar sienele
T4 - Virš Gerota ar antinkstis
| TNM stage grouping | |||
|---|---|---|---|
| Stage I | T1 | N0 | M0 |
| Stage II | T2 | N0 | M0 |
| Stage III | T3 | N0 | M0 |
| T1, T2, T3 | N1 | M0 | |
| Stage IV* | T4 | Any N | M0 |
| Any T | Any N | M1 | |
The classic triad of flank pain, visible haematuria, and palpable abdominal mass is rare (6-10%)
Paraneoplastic 30% of patients with symptomatic RCCs. A few symptomatic patients present with symptoms caused by metastatic disease, such as bone pain or persistent cough.
Computed tomography
Abdominal US and magnetic resonance (MR) imaging are supplements to CT.
Contrast-enhanced US can be helpful in specific cases (relative contraindication for contrast media, complex cystic masses, and differential diagnosis of infarction and cortical necrosis). Use for further characterisation of small renal masses, tumour thrombus and differentiation of unclear renal masses.
Magnetic resonance imaging can be used in patients with possible venous involvement, or allergy to intravenous contrast.
Computed tomography or MRI allow accurate diagnosis of RCC, but cannot reliably distinguish oncocytoma and fat-free AML from malignant renal neoplasms
For the diagnosis of complex renal cysts (Bosniak IIF-III) MRI may be an option. The accuracy of CT is limited in these cases, with poor sensitivity (36%) and specificity (76%; κ=0.11); MRI had 71% sensitivity and 91% specificity (κ=0.64). Bet paradoksas: Bosniak classification of renal cystic masses classifies renal cysts into five categories, based on CT imaging appearance, to predict malignancy risk [144,145] (LE: 3). This system also advocates treatment for each category (Table 5.1). IIF- Follow-up, up to five years.
Some are malignant. III- skirias nuo mazesniu, nes walls or septa with enhancement.-Surgery or active surveillance – Over 50% are malignant. IV-surgery
Chest CT is the most accurate for chest staging and is recommended in the primary work-up of patients with suspected RCC.
Do not use bone scan and/or positron-emission tomography (PET)-CT for staging of RCC, jei nera simptomu (yra konsensusas, kad diagnoses metu kaulu MTS buna simtomatiniai).-weak
Percutaneous renal tumour biopsies are used:
radiologically indeterminate renal masses;
to select patients with small renal masses for active surveillance;-weak
ablative ar sistemine treatments jei nera previous pathistologijos-strong
to select the most suitable form of medical and surgical strategy in the setting of metastatic disease.
Do not perform a renal tumour biopsy of cystic renal masses.-strong
Use a coaxial technique when performing a renal tumour biopsy.-strong
If a biopsy is non-diagnostic, and radiologic findings are suspicious for malignancy, a further biopsy (rebiopsijos dazniausiai) or surgical exploration should be considered
At least two good quality cores should be obtained. Peripheral biopsies are preferable for larger tumours, to avoid areas of central necrosis [163]
Combined FNA and core biopsies can provide complementary results, especially for complex cystic lesions
about 15% are benign.
The new WHO/ISUP classification will replace the Fuhrman. Are: clear cell RCC (80-90%), papillary RCC (10-15%), and chromophobe RCC (4-5%).
Histological factors include tumour grade, RCC subtype, sarcomatoid features, microvascular invasion, tumour necrosis, and invasion of the collecting system.
localised RCC (T1-2N0M0)
NSS decreased cardiac-specific mortality [218,220] as well as improved OS as compared to RN. >75 metu nera skirtumo tarp chirurginiu ir nechirurginiu budu.
Visada rinktis PN with T1 tumours
Partial nephrectomy is unsuitable:
Do not perform ipsilateral adrenalectomy if there is no clinical evidence of invasion of the adrenal gland..
Lymphadenectomy should be restricted to staging (jei ciuopi arba KT/MRT rodo). Extended lymph node dissection in patients with adverse clinical features including a large diameter of the primary tumour or sarcomatoid histological features (in high-risk patients-2b).
RCCs with tumour thrombus and no metastatic spread, prognosis is improved after nephrectomy and complete thrombectomy.
Before routine nephrectomy, tumour embolisation has no benefit. In patients unfit for surgery with massive haematuria or flank pain, embolisation can be a beneficial palliative approach.
| Summary of evidence | LE |
|---|---|
| Laparoscopic radical nephrectomy has lower morbidity than open surgery. | 1b |
| Oncological outcomes for T1-T2a tumours are equivalent between laparoscopic and open radical nephrectomy. | 2a |
GFR decline was greater in the laparoscopic PN group in the immediate post-operative period [273] ( but not after follow-up of 3.6 years.)
Simple tumour enucleation also had similar PFS and CSS rates compared to standard PN and RN in a large study [277,278].
A positive surgical margin is encountered in about 8% of PNs [263]. Studies comparing different resection techniques (open, laparoscopic, robotic) are inconclusive [264,265]. Most trials showed that intra-operative frozen section analysis had no influence on the risk of definite PSMs.
Local tumour bed recurrences were found in 16% in PSMs compared with 3% in negative margins. PSMs need not translate into worse CSS [288,289].
Offer active surveillance, radiofrequency ablation and cryoablation to elderly and/or comorbid patients with small renal masses.( Most population-based analyses show a significantly lower cancer-specific mortality for patients treated with surgery compared to non-surgical management.-LE 3)
Watchful waiting is reserved for patients whose comorbidities contraindicate any subsequent active treatment and do not require follow-up imaging ( o jei AS stebi dydi UG, KT ar MRT), unless clinically indicated.
Currently there are no data showing oncological benefit of cryoablation or radiofrequency ablation (RFA) techniques over PN ir atvirksciai, bet studijos low quality.
Adjunctive procedures such as tumour embolisation or inferior vena cava filter do not appear to offer any benefits in the treatment of tumour thrombus.
In patients with non-resectable disease, embolisation can control symptoms, including visible haematuria or flank pain, bet taikiniu terapija pries OP eksperimentine.
At present there is no evidence for the use of adjuvant therapy following surgery, jei viska pasalinai.
Trombus salinti kartu su tumour-strong
Tumour nephrectomy is curative only if all tumour deposits are excised. This includes patients with the primary tumour in place and single- or oligo-metastatic resectable disease. For most patients with metastatic disease, cytoreductive nephrectomy is palliative and systemic treatments are necessary.
| Summary of evidence | LE |
|---|---|
| Cytoreductive nephrectomy combined with interferon-α improves survival in patients with metastatic RCC (mRCC) and good performance status. | 1a |
| Cytoreductive nephrectomy for patients with simultaneous complete resection of a single metastasis or oligometastases may improve survival and delay systemic therapy. | 3 |
| Recommendations | Strength rating |
|---|---|
| Do not offer cytoreductive nephrectomy in IMDC poor-risk patients with ≥ 4 risk factors. | Weak |
| Perform immediate cytoreductive nephrectomy in patients with oligometastases when complete resection can be achieved. | Weak |
| Offer deferred cytoreductive nephrectomy to intermediate-risk patients with clear-cell metastatic RCC who require systemic therapy with sunitinib. | Weak |
| Recommendation | Strength rating |
|---|---|
| Offer local therapy for metastatic disease (including metastasectomy) to patients with favourable disease factors in whom complete resection is achievable or when local symptoms need to be controlled. | Weak |
| Offer stereotactic radiotherapy for clinically relevant bone or brain metastases for local control and symptom relief. | Weak |
| Summary of evidence | LE |
|---|---|
| Deferred cytoreductive nephrectomy with presurgical sunitinib in intermediate-risk patients with clear-cell metastatic RCC leads to a survival benefit in secondary endpoint analysis and selects out patients with inherent resistance to systemic therapy. | 2B |
| In metastatic RCC, chemotherapy is otherwise not effective with the exception of gemcitabine and doxorubicine in sarcomatoid and rapidly progressive disease. | 3 |
Interferon-alpha may only be effective in some patient subgroups, including patients with ccRCC, favourable-risk criteria, as defined by the Memorial Sloan-Kettering Cancer Center and lung metastases only. Interleukin-2, vaccines and targeted immunotherapy have no place in the standard treatment of advanced/mRCC.
1.Ipilimumab is a monoclonal antibody that binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands( jeigu APT lasteles ligandas stimuliuoja si receptoriu, tai slopinamas T - lasteles imuninis atsakas)
2.Nivolumab- Programmed cell death-1 (PD-1, also known as CD279) receptor expressed on activated T and B cells, which normally function to dampen the immune response, ji slopina prisijungdamas tumoro PD-L1. Nivolumabas neleidzia jiems susijungti.
CheckMate 214 (NCT 02231749) investigated the combination of nivolumab and ipilimumab vs. sunitinib in first-line treatment
| Recommendation | Strength rating |
|---|---|
| Use ipilimumab plus nivolumab in treatment-naïve patients with clear-cell metastatic RCC of IMDC intermediate and poor risk. | Strong |
| Offer nivolumab after one or two lines of VEGF-targeted therapy in metastatic RCC. | Strong |
| Do not offer monotherapy with interferon-α or high-dose bolus interleukin-2 as first-line therapy in metastatic RCC. | Weak |
| Do not use bevacizumab plus IFN-α in treatment-naïve clear-cell favourable- and intermediate-risk RCC patients. | Weak |
| Do not use PD-L1 tumour expression as a predictive biomarker. | Weak |
| Do not rechallenge patients who stop nivolumab plus ipilimumab because of toxicity with the same drugs in the future without expert guidance and support from a multidisciplinary team. | Strong |
Per lasteles pavirsiaus receptoriu VEGFR – aktyvuoja VEGF. Nes due to VHL-inactivation vezyje, hypoxia-inducible factor (HIF) padaugeja, kuris skatina VEGF and platelet-derived growth factor (PDGF), kurie aktyvuoja PI3 kinaze/AKT-Tirozin kinase aktyvuojasi which promote neo-angiogenesis
sunitinib 50 mg/day (four weeks on/two weeks off), Pazopanib, axitinib
Temsirolimus
Surgical resection of local recurrent disease may be offered. In cases where complete surgical removal is not feasible due to advanced tumour growth and pain, palliative treatments including radiation treatment can be considered.
There is a higher local recurrence rate after cryotherapy and RFA. For patients with metastatic disease, individualised follow-up is indicated.
| Risk profile | Surveillance | ||||
|---|---|---|---|---|---|
| 6 mo | 1 y | 2 y | 3 y | > 3 y | |
| Low | US | CT | US | CT | CT once every 2 years; Counsel about recurrence risk of ~10% |
| Intermediate / High | CT | CT | CT | CT | CT once every 2 years |
CT=computed tomography of chest and abdomen, alternatively use magnetic resonance imaging; US=ultrasound of abdomen, kidneys and renal bed.
| Recommendations | grade | |
|---|---|---|
| Intensify follow-up in patients after NSS for tumours > 7 cm or in patients with a positive surgical margin. | weak | ↑ |
| Base risk stratification on pre-existing classification systems such as the University of California Los Angeles integrated staging system integrated risk assessment score[](http://urology.ucla.edu/body.cfm?id=443). | strong | ↑↑ |