Once You Have Cancer How Likely to Get It Again Kidney Cancer
Rev Urol. 2006 Winter; 8(1): 1–vii.
Surveillance Strategies for Renal Cell Carcinoma Patients Following Nephrectomy
Abstract
Renal prison cell carcinoma (RCC) is the well-nigh lethal of urologic malignancies, accounting for an estimated 36,000 new cases of carcinoma and 12,000 deaths in 2005. Nephrectomy is the usual treatment; however, after nephrectomy, RCC recurs in 20% to 40% of patients with clinically localized affliction. A consensus surveillance protocol does not be for follow-upwards of RCC after nephrectomy. In this article, available protocols are reviewed with a goal of developing an evidence-based system including the prognostic factors for recurrent illness, chronology and sites of recurrence, available handling options if recurrent disease is found, and modalities of diagnostic testing available to urologists. New surveillance recommendations are presented based on prognostic factors as well as the University of California, Los Angeles Integrated Staging System for RCC.
Key words: Cancer, Kidney, Renal, Nephrectomy, Surveillance, Recurrence
In the United States, renal prison cell carcinoma (RCC) will account for an estimated 36,000 new cases and over 12,000 deaths in 2005.one RCC is the nearly lethal of the urologic malignancies, with approximately twenty% to 30% of patients with RCC presenting with metastatic disease and more 40% of patients eventually dying from it.1 , ii Surgical resection for clinically localized disease remains the mainstay for curative intervention. However, the aggressive and often insidious nature of RCC is reflected by recurrence rates of 20% to twoscore% after nephrectomy for clinically localized disease.2
This loftier rate of recurrence for clinically localized disease after nephrectomy underscores the importance of mail-surgical surveillance. With the availability of treatment modalities offering improved survival in recurrent cases, the physician is challenged to identify treatable recurrences, while minimizing low yield studies and without sacrificing patient outcomes.
Urologists play a prominent role in long-term follow-up of patients with RCC. However, a consensus surveillance protocol does non exist. The rationale for developing an show-based arrangement is based on the prognostic factors for recurrent disease, chronology and sites of recurrence, treatment options bachelor if recurrent affliction is found, and modalities of diagnostic testing bachelor. This article provides a historical review of surveillance protocols and discusses new recommendations based on prognostic factors besides as the University of California, Los Angeles (UCLA) Integrated Staging Organization (UISS).
Prognostic Factors in RCC
Multiple prognostic factors have been studied to aid predict RCC recurrence, including tumor stage, nuclear form, overall performance status, and molecular markers.iii However, anatomic staging systems based on the tumor, nodes, metastasis (TNM) arrangement have been the mainstays in RCC prognosis. Using the 1997 TNM classification from the International Spousal relationship Against Cancer and American Joint Committee on Cancer, v-twelvemonth cancer-specific survival rates of 91%, 74%, 67%, and 32% for stages I to Iv, respectively, take been reported.iv A major reduction in survival occurs with systemic metastases between stages III and 4.
Positive lymph node status is incorporated in the TNM classification and is associated with a higher incidence of metastatic affliction and poorer response rates to immunotherapy.v , 6 The overall incidence of lymph node metastases is approximately 20% with a five-year survival rate ranging from eleven% to 35%. Significantly, lymph node dissection in these patients improves response to immunotherapy, considering lymph nodes have been observed to respond minimally to immunotherapy.seven
Tumor grade is an independent prognostic indicator for RCC. The Fuhrman nuclear grading organisation projects v-year survival rates of 89%, 65%, and 46% for grades ane, 2, and 3 to iv, respectively, independent of T phase.four Alternatively, in patients with T1 illness, v-year cancer-specific survival rates accept been reported to exist 91%, 83%, 60%, and 0% for grades 1, 2, 3, and 4, respectively.4
Incorporated in the TNM staging system, the modified 2002 TNM classifies tumors less than 4 cm (T1a), betwixt 4 and 7 cm (T1b), and greater than vii cm. In addition to its prognostic value, size is an of import benchmark in choice for nephron-sparing surgery, with tumors 4 cm or less most acquiescent for fractional nephrectomy.8
Recurrence of RCC: Timing and Location
The greatest risk of recurrence for RCC occurs within the first v years subsequently nephrectomy, with the majority of recurrences occurring within 3 years. Although recurrences have been reported as belatedly equally 30 years following nephrectomy, rates of 43% in the first year, lxx% within the 2nd year, 80% within 3 years, and 93% within 5 years have been reported.9 , 10 Tumor stage plays an of import role in timing of recurrence, with T1 tumors generally recurring between 38 and 45 months, whereas T3 tumors generally recur between 17 and 28 months following initial nephrectomy.eleven , 12 Subsequently nephrectomy, the incidence of RCC recurrence has been reported to be 7% with a median time of 38 months for T1 tumors, 26% with a median time of 32 months for T2 disease, and 39% with a median fourth dimension to recurrence at 17 months for T3 tumors.11
RCC has been shown to metastasize to almost all soft tissues in the body, but most normally to the lung, followed past bone, liver, brain, and local recurrence.12 Metastases to brain, os, and liver often present as widely disseminated affliction. Modalities of survey are chosen to reflect the about prevalent locations of RCC recurrence. In addition, stringent surveillance to detect recurrences in areas most amenable to further therapy is paramount.
RCC metastases occur almost usually in the lung, affecting iii% to 16% of patients later nephrectomy.10 , eleven , 13 – 15 Metastatic lung lesions are typically identified through symptoms such as cough, dyspnea, pleuritic chest pain, or hemoptysis (over 70%), although other reports find that these lesions are detected in asymptomatic patients more readily through imaging tests (over ninety%).12 A history and physical test are performed, and serial chest radiographs are obtained. Nosotros found chest computed tomography (CT) scans to be more sensitive in detecting lung metastases.
Bone metastases occur in 2% to 8% of patients following nephrectomy.10 , xi , fourteen , fifteen The majority of patients present with symptoms of bone pain (67% to 90%) and with elevated alkaline phosphatase levels (33% to 55%).eleven , 16 , 17 Furthermore, treatment for bone metastases is usually palliative to prevent pain or pathologic fractures, or to preserve part, and thus routine radiographic surveillance or nuclear scintigraphy is non advocated but used for confirmation of suspected metastases.
The incidence of liver metastases is reported to be 1% to 7%.10 , 11 , xiv , 15 The majority of metastases are detected as a issue of symptoms (86% to 90%) or elevated liver role tests, although most are multifocal at the fourth dimension of diagnosis.11 , 14 As resection of liver metastases improves survival, especially resection of solitary masses, history and physical examination, laboratory studies, and surveillance intestinal CT scans are the standard of care.ii
Metastases to the encephalon occur in 2% to 4% of patients post-obit nephrectomy. 10 , eleven , fourteen , 15 Metastasis to the brain unremarkably involves neurologic symptoms in upwards to 98% of patients.17 Handling is usually palliative and typically consists of corticosteroid therapy or radiation therapy; therefore, active surveillance with imaging is not justified. Yet, at UCLA, before immunotherapy begins, brain screening with MRI is performed to evaluate for occult metastasis because the seizure threshold is decreased with interleukin-ii (IL-ii) therapy.12 Brain metastases tin can so be treated with gamma-knife surgery to better tolerance to immunotherapy.
Studies report the incidence of local recurrence ranging from 1.eight% to 27%, with 1 study reporting a 5-year incidence of one.eight% from a population undergoing nephrectomy for localized RCC.12 , 18 In the same study, only threescore% of recurrences were identified secondary to symptoms.18 Along with a conscientious history and physical examination, abdominal CT scans are critical considering resection of the renal fossa bed has been shown to improve survival.
Nephron-sparing surgery or partial nephrectomy has been advocated for localized RCC lesions generally less than four cm diameter. Despite the fears of higher local recurrence following partial nephrectomy, local recurrence rates of 1.2% to 9% accept been reported, with breakdown past T stage at 0%, 2%, eight%, and 11% for T1, T2, T3a, and T3b disease, respectively, in one study.8 , fifteen Furthermore, overall survival rates compared with radical nephrectomy have been similar for T1 tumors.8
Management of Recurrent RCC
The challenge in the management of recurrent RCC lies in the limited efficacy of treatment modalities considering RCC is typically resistant to chemotherapy and radiation therapy. Two modes of handling are currently available for metastatic or recurrent RCC: immunotherapy and surgery. Systemic IL-ii treatment, the only FDA-approved immunotherapy, exhibits response rates of fifteen% to 25%.19 This therapy includes significant side furnishings, including pulmonary edema, hypotension, flu-like symptoms, and primal nervous system toxicity, and requires acceptable renal role to tolerate treatment. Improved response to immunotherapy has been shown in patients with the everyman metastatic brunt and with lone versus multiple recurrences.20
Surgical management of recurrent RCC plays a role in solitary metastasis, locally recurrent illness, residual masses after systemic therapy, and palliation for symptomatic relief. Surgical resection of alone metastasis can result in five-year survival rates of 24% to sixty%, with solitary lung metastasis nearly amenable for resection.21 Resection of local recurrences has besides been shown to extend survival from 21 to 136 months with reported v-twelvemonth survival for patients treated with surgical resection, medical therapy, and ascertainment for renal fossa recurrences of 51%, 18%, and 13%, respectively.eighteen , 22 , 23
Based on the more favorable out-comes when metastatic burden is detected at its infancy, an appropriate but aggressive surveillance protocol is indicated. Other factors should be weighed in likewise, including general health and comorbidities, site(southward) of metastases, illness course to date, and morbidity of surgery.
Traditional Surveillance Protocols
The majority of recurrent affliction is detected by surveillance laboratory or radiographic studies in asymptomatic patients 50% to 80% of the time, with the remainder detected by either piece of work-up of patient symptoms, including decreased appetite, weight loss, decreased free energy, fever, and night sweats, or physical findings of cachexia, abdominal mass, localized neurologic symptoms, or adenopathy.ii Surveillance tools include a careful history and physical exam; laboratory tests for serum calcium level, alkaline metal phosphatase level, and liver transaminases; and plain chest radiographs and CT scans.
Traditional protocols uniformly followed patients without tailored time points reflecting the likelihood of recurrence. Montie24 proposed a generic protocol for RCC surveillance post-obit nephrectomy with a history, physical examination, and laboratory tests every 6 months for v years starting 1 calendar month following surgery, a chest radiograph every vi months starting at 6 months, and an intestinal CT scan afterward 12, 24, and 48 months. Although based largely on empirical information, the increased concern of local tumor recurrence post-obit partial nephrectomy has led to more frequent abdominal CT scans at a rate of one time every six months for 5 years.
Stage-Based Surveillance Protocols
Several protocols take been proposed based on TNM staging. They have been reviewed in greater detail elsewhere and just the range of recommendations will be summarized hither. For T1 disease, adventure of metastatic disease and local recurrence is depression, thus recommendations range from a history and physical examination yearly for 5 years follow-up, to including a chest radiograph every 6 months for three years so yearly until v years follow-up. Nigh protocols practise non advocate intestinal CT surveillance.10 , 11 , 14 , 25
Increased risk for lung and abdominal recurrence exists for T2 tumors, thus recommendations range from a history and concrete examination, laboratory tests, and chest radiograph every 6 months for three years, then yearly until 5 years with no follow-up CT scans, to a history and physical examination, laboratory tests, and chest radiograph yearly for 5 years and abdominal CT scans at 2 and 4 years.10 , eleven , 14 , 25
Surveillance for T3 and T4 illness increases intestinal CT surveillance. Along with a history and physical examination, laboratory tests, and chest radiograph every half-dozen months for 3 years so yearly until five years follow-upward, most reports advocated routine intestinal CT scans, with scans at years 2 and 5, or 1, 3, and five.10 , 11 , 14 , 25 Some reports advocate a first visit at 3 months.
Post-obit partial nephrectomy, increased frequency of abdominal CT scans was advocated for T3 affliction with scans every vi months for 3 years, then a scan at year 5 com-pared to CT scans at i, 3, and five years by the same study.25
Integrated Staging and University of California, Los Angeles Integrated Staging System-Based Surveillance Protocols
Contemporary systems have been developed at UCLA and other institutions to improve and simplify prognostic information based on TNM stage as well as other independent pathologic and clinical variables. Notably, Kattan and colleagues26 at Memorial Sloan-Kettering Cancer Middle evaluated 601 patients under-going nephrectomy for localized RCC and found symptoms, tumor histology, tumor size, and TNM phase all independent predictors of tumor recurrence. Leibovich and colleagues27 at the Mayo Clinic evaluated 1671 patients undergoing nephrectomy for localized RCC and found tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis to be predictive of progression to metastatic illness. In both studies, the described factors were used to construct a nomogram to stratify patients according to risk of metastasis.
At the University of California, Los Angeles (UCLA), a novel staging organization was recently developed that stratifies patients improve than stage alone for survival and tumor recurrence. The evolution of the UCLA Integrated Staging System (UISS) incorporated the 1997 TNM classification with the Eastern Cooperative Oncology Group (ECOG) performance condition and Fuhrman grade into a single prognostic system and has been validated using 4202 patients from 8 institutions28 , 29 (Figure 1). The UISS has undergone modification from its original form to a simplified system categorizing patients into run a risk groups of low, intermediate, and high risk30 (Figure ii). For localized RCC, five-yr survival rates from this study were 92%, 67%, and 44% for low-, intermediate-, and high-chance groups, respectively (Effigy 3). For metastatic RCC, the UISS projected 3-yr survival rates of 37%, 23%, and 12% for low-, intermediate-, and high-hazard groups, respectively.
Kaplan-Meier survival analysis of 661 patients based on prognostic indicators incorporated into University of California Los Angeles Integrated Staging Organisation for renal jail cell carcinoma. (A) Survival curves based on 1997 tumor, nodes, metastasis (TNM) stages I–IV; (B) Survival curves based on Fuhrman grades one–iv. (C) Survival curves based on Eastern Cooperative Oncology Group performance condition. Reproduced with permission from Zisman A et al.28
Academy of California Los Angeles Integrated Staging for patients with localized renal jail cell carcinoma. Using the T stage, Fuhrman form, and Eastern Cooperative Oncology Group operation status (ECOG PS), patients are stratified into low-, intermediate-, and high-risk groups. Adapted from Zisman A et al.30
Kaplan-Meier survival assay of 3119 patients based on University of California Los Angeles Integrated Staging with localized renal cell carcinoma. CT, computerized tomography; LR, low risk; IR, intermediate risk; HR, high gamble. Reproduced with permission from Patard JJ et al.29
Based on the UISS stratification, the natural history of RCC, and available treatment modalities, nosotros recommend the post-obit guidelines (Figure 4). For depression-take chances patients, nosotros recommend yearly history and concrete examination, laboratory tests, and chest CT for 5 years and an abdominal CT scan at years 2 and four, with no further surveillance beyond 5 years. For intermediate-take a chance patients, we recommend history and physical examination, laboratory tests, and breast CT every half dozen months for the showtime 3 years, and so yearly for 10 years of follow-upwards, with an abdominal CT scan at ane twelvemonth then every ii years until 10 years follow-upwardly. We recommend more than intensive intestinal surveillance for high-hazard patients, with recommendations identical to those for the intermediate-adventure group except with more frequent intestinal CT scans at a rate of once every 6 months for the outset ii years, then yearly for years ii to 5, then every two years until ten years follow-up. For both medium-and high-take chances groups, a chest radiograph can alternate with a chest CT scan after 3 years.12 , 31
Surveillance protocol post-obit nephrectomy for localized renal cell carcinoma using the Academy of California Los Angeles Integrated Staging System.
Compared to a non-biased protocol, this strategy has a more relaxed surveillance for the depression-chance grouping, with increased surveillance for the loftier-take a chance population. We do not recommend whatever additional surveillance for patients following partial nephrectomy, with an exception perhaps in cases of familial forms of RCC such every bit von Hippel-Lindau disease, with which at that place have been documented reports of fourscore% recurrence in the ipsilateral kidney following fractional nephrectomy within 10 years.32
Notably, all surveillance protocols must take into account patient comorbidities, patient compliance and mindset, and willingness to consider additional handling.
Futurity Directions
New technologies and progressive understanding of RCC biology promise enhanced treatments as well every bit detection of metastases. Positron emission tomography (PET) may soon have a larger part in renal tumor imaging. Studies suggest promising results for detection of lymph node involvement and of improved differentiation of local recurrence and metastasis.33 In a written report of 8 patients, PET imaging upstaged tumor burden in iii patients and excluded recurrence in i patient.34
The employ of molecular markers for RCC is currently in its infancy. Markers may prove benign as a prognostic indicator, to predict responsiveness to treatment, to monitor progression of treatment, to detect recurrences, and perhaps equally a target for directed therapies or vaccines. Playing essential roles in angiogenesis, apoptosis, cell adhesion, jail cell cycle regulation, and proliferation, these molecules represent the primal to un-locking the mysteries of RCC.19 Recent work in carbonic anhydrase (CA) Nine, a member of the carbonic anhydrase family of proteins thought to regulate intracellular and extracellular pH during hypoxic periods in tumor cells, has shown that low expression of CA IX, defined as less than 85%, is an independent prognostic indicator of poor survival in patients with metastatic RCC.35 , 36 Furthermore, the RCC of complete responders to immunotherapy correlated with high expression of CA IX.35 An analogous correlation exists in the low expression of CA IX in papillary and chromophobe subsets of RCC, which typically answer poorly to immunotherapy. At UCLA, CA IX is at present routinely screened in pathologic samples and a stage III trial of antibody against CA IX is underway.
In an era of express medical resource, future studies will also investigate the price-benefit analysis of aggressive routine surveillance. These data will compare the burden of early on surveillance to detect early on recurrences to the response rates and outcomes when recurrences are detected later.
Determination
Refinements in the understanding of the natural history of RCC, as well as promising new discoveries in RCC biology, event in a continuous evolution of recommendations for surveillance of patients with RCC. Currently at UCLA, a novel staging algorithm has combined prognostic factors along with the traditional TNM staging organization to improve RCC staging. Together with the likely timing and location for RCC recurrences, an evidence-based protocol to survey patients following nephrectomy for clinically localized RCC has been proposed. This protocol can exist used by the clinician with patient preferences and treatment options to tailor patient follow-upwardly after nephrectomy.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1471767/
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