117 Kidney Cancer Survivorship Challenges and Issues
RENAL DYSFUNCTION FOLLOWING NEPHRECTOMY
Renal dysfunction following nephrectomy is a recognized occurrence in survivors of cancer localized to the kidney. Mild decrease in glomerular filtration rate (GFR) is more common following radical nephrectomy than partial nephrectomy (1,2). Although nephrectomy in healthy patients does not result in clinically significant chronic renal impairment based on studies from kidney transplant donors, nephrectomy in patients with renal tumors involves a higher level of risk. In a retrospective study of patients with two healthy kidneys and normal serum creatinine (<1.4 mg/dL) who had elective partial or radical nephrectomy for a tumor that was 4 cm or smaller, the probability of new chronic kidney disease (CKD) (defined as GFR <60) at 3 years after surgery was 20% after partial nephrectomy and 65% after radical nephrectomy (1). In a separate retrospective study with a longer follow-up period that excluded patients with baseline CKD (creatinine >1.5 mg/dL), 22% of patients in the radical nephrectomy group experienced new onset CKD at 10 years, compared to 12% of patients in the nephron-sparing (partial nephrectomy) surgery group (2). However, conflicting data from a European randomized controlled trial in a similar patient population suggests that while more patients who receive radical nephrectomy compared to partial nephrectomy will subsequently experience GFR <60, the difference in the rate of patients who develop GFR <30 is not statistically significant between the 2 groups (3). In addition to the loss of functional nephrons, worsening of overall renal function may be attributed to the increase in GFR of the remaining nephrons, leading to hyperfiltration, an increase in glomerular pressure, and acceleration of preexisting renal disease (4). The rate of 118decrease in postoperative GFR in patients whose preoperative GFR is greater than 60 is widely variable in the literature.
Long-term surveillance for renal dysfunction includes following estimated GFR, quantification of any proteinuria, and review of urinalyses (5). While the gold standard for measurement of the GFR utilizes an infusion of inulin, estimation of filtration by the modification of diet in renal disease (MDRD) and Cockcroft-Gault formulas are often used for practical purposes. Proteinuria can be a marker of hyperfiltration and is associated with faster progression of CKD (2,5). This can be an indication for initiation of an angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker, both of which can have renal protective effects.
LONG-TERM EFFECTS OF TARGETED AGENTS
Data on targeted agents thus far suggests that long-term effects should not be a routine concern.
Evaluation of safety in patients with metastatic disease who received sorafenib for greater than 1 year in the phase 3 TARGET trial demonstrated no new toxic effects. Adverse effects were primarily grade 1 or 2, although 34% were grade 3 or 4. Most adverse effects, of any grade, developed in the first cycle and decreased in frequency with each subsequent cycle (6).
Similarly, data from the global expanded access program for more than 4,500 patients who were treated with sunitinib for a median of 7 months, with 12 months of posttreatment follow-up, demonstrated that the safety profile appeared unchanged with long-term follow-up. Treatment schedule was 4 weeks on with two weeks off therapy prior to initiation of the next cycle. The three most common reasons for discontinuing therapy were lack of efficacy (39%), death (21%), and adverse effects (16%) (7).
Long-term effects of pazopanib at 800 mg daily were studied in the extension study of the phase 3 placebo-controlled clinical trial. Median duration of treatment was 9.7 months, and 43% of patients received treatment for more than a year. The most common reason for discontinuation of therapy was progression 119of disease. The safety profile appeared unchanged compared to the original study in which median duration of treatment was 7.4 months, with the most common side effects being hypertension, diarrhea, hair color changes, and anorexia (8).
Pooled retrospective data of clinical trials utilizing single-agent axitinib at 5 mg twice daily demonstrated declining or stable rates of most adverse effects in patients who were treated for more than 2 years compared to those treated for shorter time periods. The exceptions were increasing amylase, and myocardial infarction, which increased from 0 during the initial 6 months of treatment to 3% and 5%, respectively, at 2 years (9).
SURVEILLANCE FOR CANCER RECURRENCE
After surgical excision of stage II or III disease, 20% to 40% of patients will experience relapse, the majority in the lungs. The optimal approach to postoperative surveillance is controversial. The American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) guidelines are the most widely referenced practice guidelines and are quite similar (10,11). They are displayed in Figures 18.1 and 18.2. Some have suggested adjustments in screening depending on histologic subtype, based on observation of different recurrence patterns (12). The majority of clear cell tumors recur in the lungs, while the majority of papillary and chromophobe tumors recur within the abdomen. Additionally, the time to recurrence is significantly longer for chromophobe tumors (mean of 7 years, compared to a mean of 3.5–4 years in clear cell and papillary carcinomas). However, alternate screening algorithms have not yet been widely adopted.
Figure 18.1 AUA/NCCN guidelines for active surveillance after surgery in low-risk disease.
AUA, American Urological Association; CMP, comprehensive metabolic panel; CXR, chest x-ray; H&P, history and physical; NCCN, National Comprehensive Cancer Network; US, ultrasound.
Figure 18.2 AUA/NCCN guidelines for active surveillance after surgery in moderate- to high-risk disease.
AUA, American Urological Association; BUN, blood urea nitrogen; CBC, complete blood count; CMP, comprehensive metabolic panel; Cr, creatinine; CXR, chest x-ray; NCCN, National Comprehensive Cancer Network; UA, urinalysis; US, ultrasound.