89Treatment of Early Stage Renal Cell Carcinoma: Surgical Approaches, Partial Nephrectomy, and Ablation
For this review, “early stage disease” of renal cell carcinoma (RCC) refers to renal masses ≤7 cm (cT1, stage I) in the absence of metastasis or lymph node involvement by imaging assessment. More than 60% of small renal masses (SRM) (≤4 cm; cT1a) are incidentally detected, with imaging performed in asymptomatic patients for unrelated abdominal or musculoskeletal complaints. With the increased imaging detection of SRM there has been an overall clinical stage migration towards cT1 renal tumors. There is a direct correlation between mass size and the risk of malignancy. Smaller lesions have a higher likelihood to be benign, while larger lesions tend to be conventional clear cell carcinomas rather than the less common renal cell subtypes (papillary, chromophobe), with every centimeter in size making it more likely to be clear cell RCC.
INITIAL ASSESSMENT OF A SMALL RENAL MASS
The initial assessment of a SRM depends critically on a high quality radiographic examination. While ultrasound may provide initial suspicion for a solid renal mass, more sophisticated multiphase CT and multi parametric MRI enable one to characterize a renal mass accurately in more than 90% of all cases (Figure 14.1).
The most important criteria in the evaluation of a solid renal mass is contrast enhancement. A lesion is generally felt to be enhancing with an increase of 10 to 20 HU on the enhanced phase (arterial and venous phase) compared to the unenhanced phase. High resolution images should provide sufficient information to plan further treatment and describe location, laterality, relationship to adjacent structures, renovascular anatomy, characteristic features, multifocality, and presence of locoregional or visceral metastasis.
Figure 14.1 (A) Multiphasic CT allows for differentiation of renal masses. A clear cell renal carcinoma typically shows (B) strong early enhancement and (C) a washout pattern, (D and E) papillary RCC commonly demonstrates a more gradual enhancement over time.
Source: Images courtesy of Tobias Franiel MD, Department of Radiology, University Hospital Jena.
Extirpative surgical options include radical nephrectomy (RN) and partial nephrectomy (PN). Open, laparoscopic, and robotic approaches have been described for each operation.
PN should be considered for all T1a and many T1b renal masses if the patient is medically fit, willing to undergo surgery, and a nephron-sparing approach is technically feasible. 91There are two concepts that support the utilization of PN over RN. The first is preservation of functional nephrons. The second is mitigating the small risk of a contralateral renal tumor later in life. The risk of a contralateral tumor after a primary RCC is estimated at about 2% to 4% and will be considerably higher in patients with Von-Hippel-Lindau Disease and other familial RCC syndromes.
The primary goal of a PN is oncologic control while maximally preserving kidney function. The European Organisation for Research and Treatment of Cancer (EORTC) trial 30904 reported a lower incidence of moderate kidney disease in patients treated with a PN versus a RN but did not observe an effect on decreasing the incidence of severe chronic kidney disease (CKD) or kidney failure between the two groups (1). There was no benefit on mortality. This may be attributed to the limited median follow-up of 9.3 years. Other reports indicate an association with CKD and a higher risk of cardiovascular disease and death. While RN appears to be associated with a higher risk of CKD, it is important to recognize that progression of worsening CKD after surgical removal of nephrons may not follow the pattern of progressive decline observed in medical CKD. There is a particularly compelling rationale for nephron sparing surgery in patients with bilateral renal masses, preexisting decreased kidney function, and risk factors for progression to CKD such as diabetes and hypertension.
Note that the Guideline on SRM from the American Urology Association now recommends PN for most clinical T1 renal masses and considers oncological outcome to be “virtually identical” (2). Open, laparoscopic, and robot-assisted approaches are utilized for PN. Numerous studies failed to demonstrate a difference in oncological outcomes among the various techniques. The surgical approach, at this point, remains the surgeon’s preference.
The most common ablative techniques for RCC include radiofrequency ablation (RFA) and cryotherapy, which are both thermal modalities. Ablation of a renal mass may be 92considered in patients with cT1a lesions. In tumors larger than 3 cm there is an increased risk of complications and local recurrence (3).
Ablation can be offered to patients not eligible for or unwilling to undergo extirpative surgery but who need or wish to receive some form of treatment. These would include very elderly or medically ill patients with rapidly growing renal masses unsuited for active surveillance. Potential advantages over extirpative surgery include decreased morbidity and shorter convalescence time. Extirpation and ablation have been reported to have similar effects on posttreatment kidney function, especially in higher risk patients with a solitary kidney (4). All ablative procedures should be preceded by a percutaneous biopsy for histological confirmation and to guide postprocedure surveillance.
Factors that guide a physician when considering an ablative approach are size, shape, and location of the lesion. In general, tumors suitable for ablation should not exceed a size of 4 cm. Proximity to critical organs such as the colon, spleen, and liver may determine feasibility of ablation. Upper pole lesions predispose to possible pleural injury. All these anatomical relationships need to be accounted for and may vary depending on the patient’s position during the procedure.
For cryoablation, oncological outcomes remain controversial as there are fewer clinical trials comparing ablative procedures to extirpative approaches. Cryoablation appears to have a higher risk of recurrence as compared to PN (5). For RFA the cancer-specific survival seems to be comparable to PN in well-selected candidates (6). The challenge of all ablative techniques is the intensity of posttreatment surveillance with cross-sectional imaging. Initially, it is important to establish whether the lesion was adequately destroyed in its entirety. Most incomplete treatments (~70%) are detected within the first 3 months after ablation. As compared to PN, assessing the status of the ablated tumor may be more difficult as the lesion has not been removed but may have been rendered nonviable. Contrast enhancement of the ablated tumor is critical to determine recurrence or persistence of disease. Enhancement of the rim is less concerning than central enhancement within the tumor. The imaging characteristics of RF and cryoablated tumors may differ postprocedure.
Active surveillance (AS) of small renal tumors is an emerging concept, as about 20% of T1 enhancing renal masses are benign. Additionally, high-grade lesions are only observed in 20% to 25% of all RCCs in this size range. Many renal masses are slow growing, with an annual increase in tumor diameter of around 0.3 cm (7). There is controversy about the requirement of a renal mass biopsy prior to entering a patient into an active surveillance protocol. Some experts feel that a biopsy can be omitted for frail patients on AS where knowledge of pathology may not change management.
According to the American Urological Association Guideline (AUA), European Association of Urology (EAU), and National Comprehensive Cancer Network (NCCN) guidelines, active surveillance is primarily an option for patients unfit or unwilling to undergo surgery. This is more suitable for elderly patients with medical comorbidities and might not be a suitable option for younger, healthier patients who may prefer definitive treatment. This is reflected by the results of the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) study that prospectively enrolled 497 patients who chose active surveillance or primary active intervention. Patients on active surveillance were older, had more comorbidities, higher Eastern Cooperative Oncology Group (ECOG) scores, smaller tumors, and more often multiple or bilateral lesions. Cancer-specific survival was 99% and 100% respectively in this cohort, supporting active surveillance as an oncologically viable and safe option for well-selected patients (8). There are no universally accepted criteria to determine who is a candidate for AS. Wolf et al. proposed a biopsy-directed management algorithm that utilizes histology and grading to designate patients for surveillance or intervention. While this is a very pragmatic approach, it has not yet been validated in a randomized clinical trial (9).
RENAL MASS BIOPSY
Histological confirmation of RCC is not a requirement during the diagnostic work-up of a solid enhancing renal mass. Currently, imaging more than histological diagnosis generally 94determines the choice of a definitive management. A renal biopsy should be performed as a core needle biopsy, which has a higher sensitivity and specificity than fine needle aspiration (10). Renal biopsy performs poorly for cystic lesions and for tumors smaller than 1 cm. The biopsy can be performed using ultrasound, CT, or MRI guidance. A renal mass biopsy has a complication rate of up to 8%. Complications are mostly related to bleeding, pain, infection, or injury of adjacent structures. Tumor seeding is an extremely rarely reported event, with only three reported cases in the last 25 years.
The true risk of a renal mass biopsy is a false negative result. Biopsies may also either miss the lesion or not collect enough viable tissue for a histopathological diagnosis. Also, it is critical to recognize that renal tumors show tremendous intratumoral heterogeneity, so a single biopsy may not adequately reflect the true malignant potential of a given tumor. The previously referenced meta-analysis reported sensitivity and specificity of 99.1% and 99.7%, respectively. A correct histological diagnosis is achieved in about 83% of cases.
The management of SRM requires an interdisciplinary treatment approach. Open and comprehensive communication among the radiologist, pathologist, urologist, medical oncologist, and interventional radiologist will improve patient selection and individual outcomes.