The Impact of NCDB-Generated Literature on the Treatment of Urologic Malignancies

In the last 30 years, the National Cancer Database (NCDB) has offered important insights into the optimal management of urologic cancers. The NCDB is the largest cancer registry in the world¹, representing approximately 70 percent of cancer diagnoses in the United States. The large number of patient data available for analysis offers unique opportunities to examine changing treatment patterns, comparison of treatment outcomes, and epidemiology. The NCDB has tracked increased utilization of neoadjuvant chemotherapy (NAC) for treatment of muscle-invasive bladder cancer (MIBC), which is supported by current guidelines, but NAC use is still lacking. In regards to prostate cancer, the NCDB has been helpful in tracking incident diagnosis in relation to USPSTF recommendations for PSA screen and has provided some insight into treatment options when higher-level data is lacking. The NCDB offers a unique opportunity for the study of exceedingly rare subsets of testicular cancer where there are no current treatment guidelines. Lastly, there has been a large shift in presentation of renal cell carcinoma (RCC) towards stage I and less incidence of metastatic disease at presentation. Here we provide a summary of major advances in bladder, prostate, kidney and testicular tumors through publications analyzing NCDB data. 

Bladder Cancer

The NCDB has helped capture bladder cancer practice trends, epidemiology, and overall survival among various treatment groups.² The NCCN guideline recommended management of muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) with radical cystectomy (RC) or in select cases definitive chemoradiation, but actual practice has fallen short. Gray et al. examined 28,691 patients with stage II-IVa MIBC showing radical cystectomy was most common treatment modality (28.7 percent), but perioperative chemotherapy use was low (NAC: 1.9 percent, adjuvant chemotherapy (AC): 10.7 percent).³ Perioperative chemotherapy was low in 1998 at 11.6 percent and only slightly increased to 16.8 percent in 2003.⁴ In addition to survival benefit, NAC appears to allow for significant pathologic downstaging when compared to radical cystectomy alone⁵; however, bladder cancer with variant history, excluding neuroendocrine tumors, do not appear to have overall survival benefit with NAC.⁶ It appears that NAC utilization is increasing from 10.2 percent to 20.8 percent between 2006 to 2010⁷ with stage III most likely to get NAC.⁸ Definitive chemoradiation alternatively showed similar overall survival in a large cohort of patients with stage II MIBC.⁹

NCDB-based papers also have helped capture the role of AC. Galsky et al., analyzing a large group of patients with MIBC from the NCDB 2003-2006, concluded that 5 year overall survival in the RC+AC group was 37 percent vs 29.1 percent in the RC alone group¹⁰. However 30 percent of patients may not be able to receive AC because of early postoperative complications.¹¹ Perioperative chemotherapy was also seen to be negatively associated with advanced age, increasing comorbidity, lack of insurance, increased travel distance, geographic location outside of the northeastern US, and lower income.⁷

Prostate Cancer

Here we summarize the 7 most cited publications using the NCDB in relation to prostate cancer. Weiner et al. demonstrated that the incidence of low-risk prostate cancer decreased from the years 2007 to 2013 to 37 percent less than that of 2004.¹² Most newly diagnosed prostate cancer patients are asymptomatic (68.7 percent) and typically have localized disease with well or moderately differentiated tumors.¹³ There appears to be an increase in the incidence of metastatic prostate cancer, especially in the age group (55-69 years) thought to benefit the most from treatment.¹² There was a 28 percent decrease in incident diagnoses of prostate cancer in the year after the USPSTF draft recommendation against PSA screening.¹⁴

Trends in the use of various treatment modalities for prostate cancer and their impact have been analyzed with the NCDB when prospective clinical trial data are lacking. Rusthoven et al. concluded that prostate radiation therapy (RT) with androgen deprivation therapy improved overall survival in men with metastatic prostate cancer; however the extent of metastatic burden could not be controlled.¹⁵ This conclusion was complimented by Löppenberg et al. which surmised that local therapy (surgery or RT) in metastatic prostate cancer reduced overall mortality; however, the greatest benefit was in patients with low tumor risk and good general health status.¹⁶ Subsequently, a large randomized trial demonstrated that only men with low metastatic disease burden benefit from prostate RT with ADT.¹⁷ The risk of bias however is a real issue with retrospective database studies. Another NCDB study¹⁸ found that dose-escalated RT was associated with improved overall survival in men with intermediate and high risk cancer but was later refuted by a large clinical trial¹⁹. One trend identified by an NCDB study²⁰ is the fall of brachytherapy use for the treatment of localized prostate cancer which appears partly due to the rapid increase in utilization of robotic prostatectomy after its advent in the early 2000s.²⁰

Testicular Cancer

Testicular cancer is the most common cause of cancer in men aged 15-35 years. 78 percent of testicular cancer cases are diagnosed in early stage with seminoma being the most common overall at 56 percent.²¹ Nonseminoma germ cell tumors (NSGCT), unlike seminomas, are much more likely to present with late: early-stage disease with a frequency of 3:2 (late: early-stage) versus 9:1 with seminomas.²¹ Using NCDB analysis, it was observed institutions dealing with higher volumes of testicular cancer had a dose dependent improvement in survival outcomes for stage II and III NSGCT.²² Stage I seminomatous germ cell tumor (SGCT) practice guidelines have shifted from radiation towards active surveillance as the preferred adjuvant treatment. The NCDB demonstrates adjuvant radiotherapy decreased from 70.8 percent to 28 percent while observation increased from 23.7 percent to 54 percent over a 13 year period.²³ There was also decreased utilization of surveillance in patients with increased T stage and tumor size, which has been consistent with data showing higher relapse rates in patients with adverse pathologic features.²³

Kamran et al., concluded no overall survival benefit of chemotherapy in stage IS disease (>95 percent survival in observation and adjuvant treatment groups).²⁴  The NCDB also has been very helpful with rare tumor such as malignant sex cord-stromal tumors (MSCST) which has no guidelines on management secondary to very scarce data. Banerji et al. used data extracted from the NCDB from 1998-2011 and found 79,120 cases of testicular cancer, of which, only 315 cases or 0.39 percent were found to be MSCST.²⁵ The treatments varied widely, but survival estimates appeared to be worse for Sertoli tumors than Leydig tumors. The NCDB may be the only realistic option to analyze this rare type of tumor.

Kidney Cancer

The NCDB has been used to illustrate stage migration of RCC. Between 1993 and 2004²⁶, the proportion of pathologic stage I cases significantly increased from 50.6 percent to 59.5 percent. Stage II cases decreased from 14.5 percent to 11.6 percent, and stage III cases had a larger decline from 22.8 percent to 16.3 percent. Stage IV cases over the 12 year period stayed roughly the same. The increased incidence of migration towards stage I tumors is likely due to the increased use of cross-sectional imaging. The mean size of stage I tumors has decreased from a mean of 4.1 to 3.6 cm between 1994 and 2004.^26,27 In a more recent NCDB analysis from 2004-2015, the RCC stage migration appeared to have stabilized after 2007.²⁸ Also more recent analysis suggest that the incidence of metastatic RCC (mRCC) is now around 11 percent when compared to previously in 1993-2004 being 30 percent of all RCC cases.²⁸ Patients with stage III and IV RCC appear to have improved survival in recent years which has been attributed to advanced systemic therapies.²⁸

Treatment patterns have changes likely reflecting stage migration. Over a 15 year period, partial nephrectomy increased from 6.3 percent to 32.2 percent of cases and ablation increased from 1.0 percent to 6.8 percent for stage I tumors.²⁹ During this time period, there were some sociodemographic disparities that exist with nephron sparing. Female gender, black race, Hispanic ethnicity, lower income, older age and treatment at community hospitals were associated with lower use of nephron sparing.²⁹  Tabayoyong et al. demonstrated more patients receiving laparoscopic and robotic partial nephrectomy have positive surgical margins than in patients receiving open partial nephrectomy (8.1 percent and 8.7 percent, respectively, vs 4.9 percent).³⁰ Lastly, the role of cytoreductive nephrectomy (CN) with or without the use of targeted therapy (TT) in select patients with mRCC remains uncertain, but the NCDB has provided some insight. Hanna et al. compiled 15,390 patients who had mRCC and received TT with NCDB from 2006-2013 and concluded that there was +9.4 month overall survival advantage in CN patients compared to non-CN patients.³¹ Similar survival benefit was found with Bhindi et al.³² To date, there has been only one randomized trial³³ related to this question, which demonstrated that Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma. Critics of this trial highlight the discrepancy of higher metastatic disease burden than NCDB cohorts suggesting that the results are not valid in the general population, and future randomized trials are needed to answer this question.¹ 

References

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