Keywords

18.1 Introduction

Staging for malignancy is the process of determining the extent of the tumor. The stage generally takes into account the tumor’s extension or invasion into the surrounding structures, involvement of regional or distant lymph nodes (LNs), and distant metastasis. Staging for the tumor is important for risk stratification, prognostication, and facilitation of comparison between groups of patients sharing similar stage defining characteristics. As the appropriate therapy and prognosis are based on tumor stage, it is imperative to stage the tumor accurately.

Staging systems for Wilms’ tumor (WT) are based exclusively on anatomical extent of the tumor. The staging is not dependent on clinical characteristics, molecular markers, histology, or biology of the tumor [1, 2]. The anatomical extent of the tumor is determined by the pathologic examination of the surgically excised tumor and sampled LNs. Thus, it is a surgico-pathologic system where both surgeons and pathologist have an important role to play.

Stage is an important criterion in the risk stratification of the WT. Advanced tumor stage at the time of diagnosis is associated with an increased risk of recurrence [3, 4]. One of the important benefits of accurate staging is that it enables the universal comparison of treatment outcomes. Multi-center trials have shown that staging still represents a major problem. The large size of the renal tumors at the time of nephrectomy results in difficulty in the assessment of its relationship with normal renal anatomical structures such as the renal sinus and the renal capsule. Thus, it is of utmost importance that the pathologist ensures to take the blocks from all the critical sites and register the location of each block accurately [1, 5].

18.2 COG and SIOP Staging

Currently, two major surgico-pathologic staging systems are in use. Children’s Oncology Group (COG) recommends upfront surgery, and staging is based on combination of operative findings at the time of immediate nephrectomy and imaging for distant metastasis [6, 7]. Operative findings determine the local stage, while the disease stage is determined by the imaging done to look for distant metastasis.

Societe Internationale D’oncologie Pediatrique (SIOP) uses the preoperative chemotherapy (ChT) approach, and staging is done after 4–6 weeks of neoadjuvant ChT as per protocol [5, 8]. Localized tumor receives 4 weeks of preoperative ChT, while metastatic WT receives 6 weeks of preoperative ChT. The staging is done again based on local operative findings and preoperative imaging to define metastatic disease. Recently, definitions that are more detailed have been introduced to aid correct staging [9].

It is important to understand the concept of local stage and disease stage in WT. The local staging is based on operative findings, while the disease staging on preoperative image findings of presence or absence of distant metastasis. The need for local radiation and its dose depends on local stage, while the disease stage determines the type and duration of ChT to the patient.

Both staging systems for WT are essentially very similar, and both have been found to be useful in predicting outcome; however, stage-wise comparison of two staging systems is not possible due to the difference in the timing of ChT relative to the surgico-pathologic evaluation [10] (Fig. 18.1) (Tables 18.1 and 18.2).

Fig. 18.1
figure 1

Tumor staging; the general concept

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Table 18.1 COG staging
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Table 18.2 SIOP staging
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Staging of WT also has changed as the data emerged during the course of multicenter trials that subgroups within stage categories have varying prognosis. The stage defınitions have been modifıed over the years, as per the available data. It was observed that patients with “local tumor spill” have significantly high rate of local recurrence in comparison to the patients without local spill, and this led to reassignment of these patients from stage II to stage III in the recent NWTS/COG staging system [11, 12].

As the appropriate therapy and prognosis is based on tumor stage, it is imperative to stage the tumor accurately. Tumor stage is a critical component of risk-stratified therapy [13]. Both the surgeon and the pathologist play an important role in correctly determining the local stage of the tumor. Diagnostic imaging as per protocol and its correct interpretation by radiologist is also warranted for the adjudication of the disease stage [14]. Initial imaging study should be able to confirm the organ of origin to be the kidney, delineate the contiguous spread of the tumor into the ureter or vena cava, status of the opposite kidney, and delineate the metastasis if present. Additionally, a computerized tomography (CT) of chest should be done in order to look for lung metastasis, as it has been found in study trials that CT-only nodules fare worse if the treatment is administered according to the local primary stage alone [15]. An interesting study was conducted by Gow et al. to find the correlation between local staging based on CT findings and histology findings. Their study concluded that there is a poor correlation of CT scan to histological staging. Therefore, therapy based solely on radiological imaging may lead to under- or overtreatment of patients. Histological assessment of the tumor should continue to be the standard for staging WTs. The authors found it consistently difficult to identify the capsular or nodal involvement thus making them unable to correctly differentiate between stage II and stage III [16]. Failure to sample the LN is one of the most frequent errors committed by the surgeon that may lead to incorrect downstaging and undertreatment to the patient thereby leading to increased risk of local relapse [14]. The operating surgeon must be aware of the surgical factors that may upstage the tumor to avoid any such mishap. These factors include tumor spillage, transection of the tumor thrombus, removing the tumor piecemeal, etc. [16,17,18]. It is the duty of the operating surgeon to document the operative findings in detail.

The pathologist is expected to gross the specimen correctly and extensively. He/she must ensure to take the blocks from all the critical sites and document the site of each block correctly [9].

18.3 Salient Differences Between the SIOP and COG Staging System

Surgico-pathologic staging in COG staging system is done upfront while in SIOP this staging is done after neoadjuvant ChT. Upfront surgery in COG protocol provides the unique opportunity to do the histological examination of naïve tumor tissue. It also avoids unnecessary preoperative ChT to the benign tumor. In addition, it also avoids the inappropriate preoperative ChT to the tumors with histology other than WT. In contrast, preoperative ChT as per SIOP protocol decreases the tumor size, leads to favorable stage distribution, and reduces the chances of tumor rupture. This significant benefit reduces the need for radiotherapy to almost half of that required in upfront surgery protocol of COG. SIOP staging is often criticized for under-staging the WT patients. However, patients’ stages as I or II by SIOP have the same overall and event-free survival as COG stages I and II, thus invalidating the argument of under-staging against SIOP [19]. Another criticism is that it may lead to unnecessary pre-nephrectomy ChT to the benign renal tumors. The SIOP rebuttal is that this incidence is only 1.5%, and it is well balanced by the favorable stage distribution and lower risk of tumor ruptures [19, 20].

Important points to remember:

  1. 1.

    The tumor extending into renal pelvis and ureter does not upgrade the tumor, if it can be removed in toto as the tumor specimen without transecting through the tumor. On the contrary, if the tumor in the ureter is transected at the time of surgery, then it upstages the tumor to stage III. If the tumor extends along the ureter through the uretero-vesical junction and is dipping into the bladder, then the surgeon should remove the cuff of bladder around the uretero-vesical junction so as to remove the tumor in a single piece avoiding the transection through the tumor. This will prevent the tumor to be upstaged to stage III based on surgical resection margin.

  2. 2.

    The tumor extending into renal vein or inferior vena cava makes it minimum stage II.

  3. 3.

    Extension of the primary tumor within the thoracic vena cava or heart that is removed piecemeal or separately from tumor is considered stage III not stage IV, even though outside the abdomen [10].

  4. 4.

    Any residue, even when it is microscopic, makes the tumor stage III.

  5. 5.

    Positive LN makes the tumor stage III, but if the positive LN is present outside the abdominal cavity, then it will be considered metastasis and stage IV.

  6. 6.

    FNAC of the tumor does not upstage the tumor. In COG, core needle biopsy upstages the tumor to stage III.

  7. 7.

    Core needle biopsy will not upstage the tumor in SIOP. However, open biopsy will upstage the tumor to stage III in both SIOP and COG staging system,

  8. 8.

    Even in those with stage IV disease, local stage is still a prognostic feature.

  9. 9.

    In case of a bilateral WT, a local stage should be provided for each tumor.

18.4 Role of Surgeon in Appropriate Staging

  1. 1.

    Trans-peritoneal incision for wide exposure—retroperitoneal surgery may not be able to stage the tumor correctly.

  2. 2.

    The peritoneum and liver should be examined to look for any tumor implant; presence of it will upstage the tumor to stage III or stage IV, respectively. Exploration of the contralateral kidney is no longer mandated before nephrectomy if the preoperative CT or Magnetic resonance imaging (MRI) demonstrates a normal kidney [21].

  3. 3.

    Thorough inspection should be done to look for any evidence of preoperative or intraoperative rupture. Bloody peritoneal fluid suggests rupture, and surgeon should thoroughly inspect the tumor surface. Free communication of the open neoplastic tissue surface with peritoneal cavity is also a sign of tumor rupture. Rupture of the tumor upstages it to stage III.

  4. 4.

    Tumor dissection should be done carefully to prevent any intra-operative spill or tumor rupture during surgery; this will upstage the tumor to stage III [16]. “Spill” refers to a break in the tumor capsule during surgery, whether accidental, unavoidable, or by design. In COG protocol, spill is considered to have occurred if a preoperative or intraoperative needle or open biopsy is performed, thus, upstaging the tumor to stage III. Any tumor spill increases the risk of local tumor recurrence [17, 18]. In SIOP protocol, fine needle or Tru-cut needle biopsy is permitted and does not upstage the disease, while the incisional biopsy upstages it to stage III. In the United Kingdom Children’s Cancer and Leukemia Group (UKCCLG) trial, preoperative percutaneous cutting needle biopsy, preferably using coaxial technique through retroperitoneal route to obtain multiple core biopsies, used to be performed routinely in all cases at diagnosis [9].

  5. 5.

    Ureter and renal vessels should be palpated to look for any tumor extension, if the tumor extension is present then it mandates the appropriate technique so as to avoid any transection of the tumor; this will also upstage the tumor to stage III [9].

  6. 6.

    LN sampling: Failure to sample the LNs is the most frequent error committed by the surgeon [22]. This will falsely under-stage the disease leading to undertreatment and high risk of local recurrence. Pathologic assessment of hilar and regional LNs is critical to accurately stage a child with WT. Determination of the involvement of the tumor by simply looking at the LN is highly inaccurate. There is no formal recommendation on the number of lymph nodes that need to be sampled. In a retrospective study of COG, sampling of seven LNs increased the rate of detection of metastasis [23]. Another important point is that the LN even when it contains only necrotic tumor then also it is labelled as stage III in SIOP protocol [9].

  7. 7.

    Proper documentation of intraoperative findings is also one of the primary goals of the surgeon.