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. 2018 Jul 24;53(6):5106–5128. doi: 10.1111/1475-6773.13014

Medical Care Costs for Recurrent versus De Novo Stage IV Cancer by Age at Diagnosis

Debra P Ritzwoller 1,✉, Paul A Fishman 2,3, Matthew P Banegas 4, Nikki M Carroll 1, Maureen O'Keeffe‐Rosetti 4, Angel M Cronin 5, Hajime Uno 5,6, Mark C Hornbrook 4, Michael J Hassett 5,6
PMCID: PMC6232408  PMID: 30043542

Abstract

Objective

To address the knowledge gap regarding medical care costs for advanced cancer patients, we compared costs for recurrent versus de novo stage IV breast, colorectal, and lung cancer patients.

Data Sources/Study Setting

Virtual Data Warehouse (VDW) information from three Kaiser Permanente regions: Colorado, Northwest, and Washington.

Study Design

We identified patients aged ≥21 with de novo or recurrent breast (n de novo = 352; n recurrent = 765), colorectal (n de novo = 1,072; n recurrent = 542), and lung (n de novo = 4,041; n recurrent = 340) cancers diagnosed 2000–2012. We estimated average total monthly and annual costs in the 12 months preceding, month of, and 12 months following the index de novo/recurrence date, stratified by age at diagnosis (<65, ≥65). Generalized linear repeated‐measures models controlled for demographics and comorbidity.

Principal Findings

In the pre‐index period, monthly costs were higher for recurrent than for de novo breast (<65: +$2,431; ≥65: +$1,360), colorectal (<65: +$3,219; ≥65: +$2,247), and lung cancer (<65: +$3,086; ≥65: +$2,260) patients. Conversely, during the index and post‐index periods, costs were higher for de novo patients. Average total annual pre‐index costs were five‐ to ninefold higher for recurrent versus de novo patients <65.

Conclusions

Cost differences by type of advanced cancer and by age suggest heterogeneous patterns of care that merit further investigation.

Keywords: Medical care costs, advanced cancer

Individuals diagnosed with advanced cancer comprise a sizeable proportion of cancer‐related deaths and are responsible for substantial morbidity and spending in the United States (USA). There are two ways to develop advanced, noncurable cancer—be diagnosed with de novo metastatic stage IV cancer (i.e., the first occurrence of cancer) or develop recurrent metastatic cancer after previously having been treated for early‐stage (i.e., stages I–III) disease. Given that most population‐based datasets (including SEER and state‐based tumor registries) cannot identify recurrent cancers (Warren and Yabroff 2015), little is known about whether there are cost differences between patients with de novo and recurrent metastatic cancers. In addition, many cost‐effectiveness analyses associated with treatment trials for patients with metastatic cancer fail to differentiate between de novo versus recurrent metastatic cancer postdiagnosis cost trajectories (Takeda et al. 2007; Lange et al. 2014).

There are several reasons why the medical care and costs of patients with different types of advanced cancer might differ significantly. In contrast to patients with newly diagnosed cancer, those with a metastatic recurrence have been previously treated with surgery, systemic therapy, and/or radiotherapy and may therefore be ineligible for standard, first‐line treatment (Jassem et al. 2009). They may have “late effects” and/or comorbid conditions resulting from their prior disease and treatment (Carver et al. 2007); the treatments and costs for their initial, nonmetastatic cancer diagnosis may extend for many months (Eisen et al. 2015); and surveillance‐related utilization and costs after the completion of curative treatment for their initial cancer diagnosis may be significant (Khatcheressian et al. 2006; Backhus et al. 2014; Steele et al. 2015; Hahn et al. 2016). In addition, the experience of having recurrent disease after an attempt of curative therapy may lead to a shift in patients’ treatment goals and values (Weeks et al. 2012).

A number of studies have described the variation in utilization and costs associated with the initial treatment for cancer patients diagnosed at late stage versus early stage (Riley et al. 1995; Taplin et al. 1995; Warren et al. 2008; Yabroff et al. 2008, 2011). Several studies have described the high cost of care for breast cancer recurrence (Lamerato et al. 2006; Karnon et al. 2007; Lidgren et al. 2007; Engel‐Nitz et al. 2015), and others have generated cost estimates for metastatic disease in patients 65 years and older (Yabroff et al. 2009; Bradley et al. 2017). However, in many of the databases used to generate these estimates, cancer recurrence cannot be identified reliably. This raises concern that cost estimates associated with the surveillance or survivorship phases of care, as well as those associated with the advanced disease phase of care, could be biased. For example, health care costs incurred because of recurrence after definitive treatment for early‐stage disease could be attributed to the survivorship phase rather than the advanced disease phase of care. The extent of this potential bias is not well understood (Brown et al. 2002; Mariotto et al. 2011; Yabroff et al. 2011; Guy et al. 2013). In addition, few population‐based datasets are available for the estimation of cancer care‐related utilization and costs for patients less than 65 years of age. To address the lack of data related to the direct medical costs of cancer recurrence, we estimated average total annual and monthly medical care costs for patients diagnosed with recurrent breast, colorectal, or lung cancer, relative to patients diagnosed with de novo disease. We estimate costs not only among Medicare aged‐eligible patients (age ≥ 65 years) but also among those under age 65 at diagnosis, a group that we hypothesize will receive more aggressive (and more expensive) treatment for both recurrent and de novo metastatic cancers.

Methods

Data Sources

Data for this study were obtained from the Cancer Research Network's (CRN) Virtual Data Warehouse (VDW) at the Colorado, Northwest, and Washington (formerly Group Health Cooperative) Kaiser Permanente regions. The CRN (http://crn.cancer.gov/) is a consortium of large health care systems affiliated with the Health Care Systems Research Network and the National Cancer Institute (Chubak et al. 2016). The VDW contains administrative, electronic health record (EHR) and other clinical data that have been extracted, processed, and maintained at each site (Ross et al. 2014). Cancer diagnoses were obtained from the Virtual Tumor Registry (VTR) component of the VDW, which adheres to standards of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program and the North American Association of Central Cancer Registries (NAACCR) (North American Association of Central Cancer Registries 2011). VTR data are derived from certified tumor registrars’ manual review of patients’ medical records and include demographics, diagnosis date, and tumor characteristics. VTR and VDW data are linked through a common, unique patient identifier (Ritzwoller et al. 2012, 2013, 2014; Hassett et al. 2014). Diagnosis and procedure‐coded events are based on International Classification of Diseases, 9th and 10th revisions, Clinical Modification (ICD9 and ICD10), Healthcare Common Procedure Coding System (HCPCS), and the fourth edition of the Common Procedure Terminology codes (CPT‐4). Oral and infused chemotherapy and immunotherapy were captured in the VDW infusion, pharmacy, and procedure files using methods previously described (Ritzwoller et al. 2013, 2014; Carroll et al. 2017). The VDW includes geocoded measures of socioeconomic status (e.g., median family income, and education) where patients’ residential addresses are mapped to census block data using geocoding software. Deaths are derived from the tumor registries, membership data, state mortality files, and social security administration data. IRB approval was obtained from all three sites. All analyses were performed using SAS v9.4 (SAS Inc., Cary, NC).

Study Sample

We identified patients diagnosed with de novo breast, colorectal, or lung cancers between January 1, 2000, and December 31, 2011, and patients who developed recurrent disease between January 1, 2000, and December 31, 2012, after having been initially diagnosed with stages I–III breast, colorectal, or lung cancer between January 1, 2000, and December 31, 2011. All de novo patients were identified from the VTR. Recurrent disease patients from KPCO and KPNW were identified through their respective VTRs, and those from KPWA were identified using our previously reported recurrence detection and timing algorithm (Hassett et al. 2014, 2017; Ritzwoller et al. 2017). Consistent with our previous analyses, eligibility for inclusion in the recurrence group was limited to patients who: (1) had no cancer prior to their incident breast, lung, or colorectal diagnosis; (2) completed definitive local–regional therapy for their incident cancer; and (3) survived and were followed for at least 30 days after definitive therapy. Censoring occurred if the VTR identified a second primary cancer. The date of the de novo or recurrent cancer diagnosis was considered the index date for this analysis. Patients were followed from 1 year prior to index date until death, disenrollment from the health plan, or one‐year post‐index date, whichever came first. Patients who disenrolled or were alive at the end of the study were censored as of those dates.

Utilization Measures

We examined inpatient, chemotherapy, and hospice use in the 12 months post‐index date for de novo and recurrent cases across all three cancer cohorts. For recurrent cases, we also examined the proportion of cases who received chemotherapy and radiotherapy at the initial (i.e., incident stages I–III) diagnosis and in the twelve months after the index date (i.e., the recurrence date).

Costs

Medical care costs were estimated using the standard relative resource cost algorithm (SRRCA) (O'Keeffe‐Rosetti et al. 2013). SRRCA applies uniform cost coefficients to standardized claims or EHR‐derived utilization data to ensure that observed differences are not a result of differing pricing methods and billing rules (bundling of services). These estimates do not, however, account for variation in patient cost sharing or co‐pays. Costs were reported in 2012 U.S. dollars. Average total monthly and annual costs were estimated from 1 year before the index date until disenrollment, death, or 1 year after the index date. For the monthly cost analysis, the calendar month associated with the index date was considered the index month.

Statistical Analysis

Patient characteristics were reported as means, medians, and standard deviations for interval‐level variables (pre‐index, index month, post‐index) and percentages for categorical variables. Wilcoxon's rank‐sum tests (for interval‐level variables) and chi‐square tests of association (for categorical variables) were used to assess differences between the de novo and recurrent groups for all three cancer cohorts.

Differences in total annual and monthly costs between de novo versus recurrent cases were estimated separately for each cancer site across all age groups (and separately for patients aged <65 vs. ≥65) using generalized linear repeated‐measures regression models with a gamma distribution and log link (Manning, Basu, and Mullahy 2005; Basu and Manning 2010; Guy et al. 2013). We also ran the generalized linear repeated‐measures regression models where monthly costs were grouped into three‐time periods: 12 months pre‐index, index month, and 12 months post‐index. The following covariates were included in the final adjusted model: age at index date, race/ethnicity, the Quan adaptation of the Charlson comorbidity index modified to exclude cancer diagnoses (Quan et al. 2005), census‐based proxy for median family income, health plan (KPCO, KPNW, KPWA), index year, presence of an inpatient event within 12 months post‐index date, receipt of chemotherapy within 12 months post‐index date, and whether the individual died in the last month for which data were available. We address the potential bias in cost estimates due to differential follow‐up among individuals that either disenrolled or died within 12 months following the index date using inverse proportional weights (IPWs), which account for key demographic and clinical factors related to differential follow‐up. There were no significant differences in follow‐up data among recurrent and de novo breast cancer patients, but there were differences in follow‐up time among patients with lung and colorectal cancers.

Results

Demographic and Clinical Characteristics

We identified 352 breast, 1,072 colorectal, and 4,041 lung cancer cases of de novo disease, along with 765 breast, 542 colorectal, and 340 lung cancer cases of recurrent disease after an early‐stage initial diagnosis (see Figure S1: Consort Flow Diagram). As described in Table 1, relative to the recurrent cases, de novo colorectal and lung cancer patients were younger, and de novo lung cancer cases were more likely to be male. No clinically significant differences were found in race/ethnicity for de novo versus recurrent cases. Recurrent colorectal and lung cancer patients differed (higher) significantly (p < .054) in based proxies of income distribution. The year of the advanced cancer diagnosis, defined as the index year for this analysis, was relatively evenly distributed for de novo patients across all three cancer types. However, due to the study inclusion criteria (incident stages I–III diagnosis from 2000 to 2011 with a recurrent diagnosis through December 31, 2012), the recurrent cases were more heavily distributed during the latter years of the study. The comorbidity burden was statistically significantly higher only for the de novo lung cancer cases (relative to recurrent cases). A recurrence within 12 months of definitive therapy occurred in 18 percent, 31 percent, and 45 percent of the breast, colorectal, and lung cancer cases, respectively. In addition, relative to the recurrent cases, a larger proportion of the de novo colorectal (50 percent vs. 39 percent) and lung (71 percent vs. 52 percent) cancer cases died before the end of the study. The proportion of de novo cases who had at least one inpatient event after the index date was statistically significantly higher than the recurrent cases with 53 percent versus 42 percent for breast (p < .001), 76 percent versus 57 percent for colorectal (p < .001), and 60 percent versus 50 percent for lung cancers (p < .001), respectively. No statistically significant differences existed in the proportion of de novo versus recurrent cases who received chemotherapy or radiotherapy post‐index date, across all three cancer sites. For recurrent cases, receipt of chemotherapy both at the initial (stages I–III) diagnosis and during the 12 months after the index date (recurrence) was higher for breast (51 percent) than colorectal (45 percent) or lung (22 percent). The use of radiotherapy in both time periods was also higher for breast (25 percent) than for colorectal (4 percent) or lung (12 percent). No statistically significant difference in hospice use was found for de novo versus recurrent colorectal or lung cancer cases; however, the hospice use for de novo breast cases was significantly lower than recurrent cases (6 percent vs. 12 percent, p‐value .003).

Table 1.

Demographics of De Novo and Recurrent Cohorts by Cancer Site

Breast Cancer Colorectal Cancer Lung Cancer
De NovoN (%) RecurrentN (%) p‐Value De NovoN (%) RecurrentN (%) p‐Value De NovoN (%) RecurrentN (%) p‐Value
Total cases 352 765 1,072 542 4,041 340
Demographics
Race/ethnicitya
White 297 (84) 638 (83) .6241 840 (78) 434 (80) .1070 3,424 (85) 287 (84) .7619
Nonwhite 38 (11) 79 (10) 115 (11) 66 (12) 353 (9) 33 (10)
Unknown 17 (5) 48 (6) 117 (11) 42 (8) 264 (7) 20 (6)
Female 352 (100) 765 (100) NA 525 (49) 248 (46) .2217 1,949 (48) 183 (54) .0475
Age on index date
21–54 years 113 (32) 238 (31) .8243 244 (23) 76 (14) .0002 432 (11) 21 (6) .0292
55–69 years 126 (36) 267 (35) 379 (35) 214 (40) 1,672 (41) 144 (42)
70+ years 113 (32) 260 (34) 449 (42) 252 (47) 1,937 (48) 175 (52)
<65 years 214 (61) 421 (55) .0708 486 (45) 201 (37) .0015 1,450 (36) 109 (32) .1573
Mean age at index (SD) 61.6 (13.5) 62.5 (14.7) .3240 66.1 (13.6) 68.2 (12.3) .0032 68.3 (10.5) 69.0 (9.4) .2067
Income (census block level based)
<$40,000 22 (6) 79 (10) .0821 110 (10) 47 (9) .0331 490 (12) 34 (10) .0541
$40,000–$60,000 125 (36) 252 (33) 397 (37) 190 (35) 1,610 (40) 140 (41)
$60,000+ 205 (58) 434 (57) 565 (53) 305 (56) 1,941 (48) 166 (49)
Health Care System (HCS)
HCS #1 134 (38) 282 (37) .7544 356 (33) 188 (35) .0180 1,378 (34) 124 (36) .0529
HCS #2 110 (31) 231 (30) 364 (34) 148 (27) 1,201 (30) 80 (24)
HCS #3 108 (31) 252 (33) 352 (33) 206 (38) 1,462 (36) 136 (40)
Clinical characteristics
Diagnosis index year
2000–2003 93 (26) 109 (14) <.0001 341 (32) 114 (21) <.0001 1,268 (31) 68 (20) <.0001
2004–2006 84 (24) 183 (24) 270 (25) 151 (28) 1,074 (27) 93 (27)
2007–2009 94 (27) 234 (31) 287 (27) 165 (30) 1,018 (25) 94 (28)
2010–2012 81 (23) 239 (31) 174 (16) 112 (21) 681 (17) 85 (25)
Stageb
I 0 (0) 200 (26) NA 0 (0) 51 (9) NA 0 (0) 177 (52) NA
II 0 (0) 348 (46) 0 (0) 165 (30) 0 (0) 86 (25)
III 0 (0) 217 (28) 0 (0) 326 (60) 0 (0) 76 (22)
IV 352 (100) 0 (0) 1,072 (100) 0 (0) 4,042 (100) 0 (0)
Comorbidities
0 246 (70) 554 (72) .5873 609 (57) 283 (52) .1186 2,047 (51) 96 (28) <.0001
1 64 (18) 134 (18) 231 (21) 140 (26) 953 (24) 130 (38)
2+ 42 (12) 77 (10) 232 (22) 119 (22) 1,041 (26) 114 (34)
Recurrence within 12 months of definitive therapyc – 136 (18) – 170 (31) – 152 (45)
Death within 12 months post‐index date 95 (27) 242 (32) .1161 532 (50) 211 (39) <.0001 2,879 (71) 177 (52) <.0001
Inpatient event within 12 months post‐index date 186 (53) 319 (42) .0005 819 (76) 307 (57) <.0001 2,414 (60) 170 (50) .0007
Chemotherapy within 12 months post‐index date 240 (68) 529 (69) .7454 704 (66) 349 (64) .6099 2,601 (64) 223 (66) .6509
Chemotherapy at initial diagnosis and within 12 months post‐index NA 386 (50) – NA 241 (44) – NA 76 (22) –
Radiotherapy within 12 months post‐index 137 (39) 327 (43) .2282 165 (15) 88 (16) .6595 1,997 (49) 157 (46) .2738
Radiotherapy at initial diagnosis and within 12 months post‐index NA 194 (25) – NA 19 (3.5) – NA 39 (11) –
Hospice within 12 months post‐index 22(6) 92 (12) .0031 134 (13) 54 (10) .1335 732 (18) 58 (17) .6283
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a

Nonwhite includes Hispanic, black, Asian, and other races and/or ethnicities.

b

For lung cancer cohorts, de novo includes stages IIIB and IV, while recurrent includes stages I, II, or IIIA (at initial diagnosis).

c

Definitive therapy is defined mastectomy/lumpectomy for breast cancer, colectomy for CRC, and lobectomy for lung cancer, with or without radiation.

Costs

Adjusted total monthly medical care costs for 12 months before and after the index date for patients with de novo versus recurrent breast, lung, or colorectal cancers appear in Figures 1, 2, 3, respectively. Separate estimates are provided for individuals over and under 65. For all cancer types, monthly costs during the pre‐index period were significantly higher (p < .0001) for recurrent cancer patients than for de novo patients, through approximately 1 month prior to the index month (Figures 1, 2, 3 and Table 2). During the index month, monthly costs were considerably higher for de novo than for recurrent cancer patients for both colorectal cancer age groups (p < .0001) and lung cancer patients aged 65 and older (p < .0001). Higher costs were observed for all de novo breast cancer patients and for lung cancer patients aged less than 65, relative to recurrent patients, although these results did not reach statistical significance. Monthly costs between post‐index month 1 and month 12 were statistically significantly higher among de novo than among recurrent patients for all cancers and all age groups. Table S1 describes the final parameter estimates.

Figure 1.

Figure 1

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Breast Cancer Adjusted Average Monthly Total Cost by Age Group

Figure 2.

Figure 2

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Colorectal Cancer Adjusted Average Monthly Total Cost by Age Group

Figure 3.

Figure 3

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Lung Cancer Adjusted Average Monthly Total Cost by Age Group

Table 2.

Cost Estimates by Cancer Site and Age Group

Adjusted Average Total Monthly Costs
<65 Years of Age at Index Date ≥65 Years of Age at Index Date
Average Monthly Cost [$] (95% CI) Average Monthly Cost [$] (95% CI)
De Novo Recurrent Cost Difference p‐Value on Cost Differencea De Novo Recurrent Cost Difference p‐Value on Cost Differencea
Breast
12 months pre 305 (236–394) 2,737 (2,337–3,205) 2,431 <.0001 818 (608–1,099) 2,178 (1,843–2,776) 1,360 <.0001
Index month 7,926 (6,564–9,572) 7,099 (5,985–8,421) −827 .1087 9,210 (7,309–11,607) 6,530 (5,396–7,903) −2,679 .1391
12 months post 8,559 (7,398–9,904) 7,817 (6,896–8,859) −742 .0690 5,816 (4,852–6,972) 4,772 (4,213–5,406) −1,043 .0967
Colorectal cancer
12 months pre 448 (336–595) 3,667 (3,067–4,383) 3,219 <.0001 878 (749–1,029) 3,125 (2,701–3,616) 2,247 <.0001
Index month 13,588 (11,838–15,596) 5,601 (4,450–7,050) −7,987 <.0001 15,500 (13,468–17,836) 7,093 (5,778–8,708) −8,406 <.0001
12 months post 8,694 (7,724–9,785) 6,217 (5,334–7,247) −2,476 <.0001 7,024 (6,221–7,932) 5,274 (4,587–$6,063) −1,750 .0004
Lung cancer–Outliers Removedb
12 months pre 582 (507–669) 3,669 (3,140–4,287) 3,086 <.0001 1,025 (938–1,121) 3,286 (2,914–3,705) 2,260 <.0001
Index month 10,980 (10,152–11,876) 8,724 (6,757–11,263) −2,256 .0821 10,314 (9,946–11,029) 6,138 (5,018–7,509) −4,175 <.0001
12 months post 7,148 (6,722–7,602) 5,592 (4,673–6,690) −1,556 .0071 5,498 (5,203–5,811) 4,505 (3,989–5,089) −993 .0013
Adjusted Average Annual Total Cost
<65 years of Age at Index Date ≥65 years of Age at Index Date
Total Cost [$] (95% CI) Total Cost [$] (95% CI)
De Novo Recurrent Cost Difference p‐Value on Cost Differencea De Novo Recurrent Cost Difference p‐Value on Cost Differencea
Breast
12 months pre 3,310 (2,563–4,274) 30,531 (26,149–35,649) 27,221 <.0001 9,596 (7,103–12,964) 24,797 (21,118–29,117) 15,201 <.0001
Index month + 11 months post 90,391 (79,197–103,166) 72,243 (64,492–80,926) −18,148 .0005 55,436 (47,112–65,238) 44,378 (39,703–49,602) −11,058 .0086
Colorectal cancer
12 months pre 4,721 (3,331–6,690) 40,424 (33,359–48,991) 35,703 <.0001 11,558 (9,730–13,729) 36,702 (31,650–42,565) 25,144 <.0001
Index month + 11 months post 79,809 (70,735–90,048) 54,956 (46,859– 64,453) −24,853 <.0001 59,623 (53,690–66,210) 43,726 (37,702–50,322) −15,897 .0001
Lung cancer – Outliers removedb
12 months pre 6,508 (5,628–7,525) 41,973 (35,789–49,232) 35,465 <.0001 11,286 (10,288–12,383) 36,195 (31,758–41,249) 24,909 <.0001
Index month + 11 months post 64,582 (60,240–69,230) 52,759 (45,437–61,261) −11,823 .0057 41,919 (39,410–44,587) 39,854 (35,710–44,480) −2,065 .3236
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a

Differences in cost based on log values.

b

Outliers removed by adjusting all costs outside of the 99th percentile to overall mean cost.

Differences in adjusted average total monthly costs were consistent with the adjusted average total annual costs—for both the 12‐month period before and the 12‐month period after the index diagnosis (Table 2). Recurrent cancer patients had statistically significantly (p < .005) higher annual costs relative to de novo patients in the pre‐index period, for all age groups and all three cancer sites. For example, women less than 65 had an average total annual cost of $3,310 [95% CI $2,563–$4,27] in the year prior to a de novo breast cancer diagnosis, compared to $30,531 [95% CI $26,149–$35,649] in the year prior to a recurrence diagnosis, for an estimated annual cost difference of $27,221 (de novo vs. recurrence, p < .0001). For CRC and lung cancer patients less than 65, the average annual cost differential (de novo vs. recurrence) was estimated at $35,703 (p < .0001) and $35,465 (p < .0001), respectively. For patients aged 65 and older, the differentials were not as large, but remained statistically significant, with the exception of lung cancer patients. For the 12‐month period starting with and extending beyond the index month, average annual costs were greater for de novo versus recurrent cancer patients for all cancer types and age groups (Figures 1, 2, 3); all differences were statistically significant (p < .006) for all groups, except for lung cancer patients aged 65 years and older (−$2,065, p = .33).

Discussion

Our study illuminates the striking differences in overall medical care costs for de novo versus recurrent cancers. Most notable was the difference in annual total costs between the two groups in the months prior to the index advanced cancer diagnosis. For patients less than 65 years of age, estimated medical care costs during the year prior to a diagnosis of a recurrence were approximately five‐ to ninefold higher than during the year prior to a diagnosis of de novo metastatic disease. Much of this difference may be explained by residual treatment for the initial cancer diagnosis and ongoing surveillance costs (Loggers et al. 2014; Chang and Gould 2017; Merkow et al. 2017), but further analyses are warranted to determine the relative importance of these factors as contributors to this difference. Regardless, the high cost of medical care for patients previously treated for early‐stage disease illustrates the need for accessible and assessable guideline‐based surveillance care. This is particularly important for patients less than 65 years of age, who are the most vulnerable with respect to access to health insurance (Thorpe and Howard 2003; Davidoff et al. 2015).

Medical care costs during the index month of the advanced cancer diagnosis spiked. This jump was especially notable for de novo patients, relative to those with recurrent cancer. This spike in costs, and the corresponding spike in utilization (Figures 1, 2, 3), is consistent with our previous work, which noted a one‐ to threefold increase in monthly utilization of total medical care services during the months leading up to an initial cancer diagnosis (Hornbrook et al. 2013). De novo patients were younger and in the lung and colorectal cohorts less likely to survive for 12 months after the index diagnosis (Table 1) than recurrent patients, but it is not clear that these factors were responsible for the de novo/recurrent cost differential. We identified higher inpatient use for de novo cases, suggesting that the cost differential could be driven by hospitalizations and tests/procedures performed to evaluate the new cancer diagnosis. Patients with recurrent cancer previously had diagnostic studies for their initial cancer diagnosis, so it would not be surprising to expect relatively lower “evaluative” costs at the time of their cancer recurrence diagnosis. While cost differences (de novo vs. recurrent) during the index month were lower for all cancer types, the differences were not statistically significant for breast cancer patients or for lung cancer patients less than 65.

Cost differentials persisted throughout the 12‐month post‐index period. These differences were reflected in the significantly lower average total annual costs for patients with recurrent versus de novo disease (except for breast cancer patients). Some have suggested that the use of aggressive and expensive initial treatments (Sagar, Lin, and Castel 2017) and/or end‐of‐life care could be driving costs for de novo cases. However, we found no significant differences between groups with respect to the proportion who received chemotherapy or radiotherapy in the 12 months following the index date. Across all cohorts, a minority of recurrent cases received chemotherapy in both the initial and recurrent settings (Yardley et al. 2014; Rier et al. 2017). Perhaps, providers are less likely to recommend aggressive, expensive therapy for recurrent versus de novo cases, because patients with recurrence may be relatively chemoresistant, whereas de novo cases are inherently chemotherapy naïve and may be more likely to benefit from therapy (Malmgren et al. 2018). The average total annual cost estimates further illuminate the cost differences between groups (de novo vs. recurrent) by period (pre‐/post‐index). Also, we noted higher costs for patients in the younger age group—a finding previously noted by Taplin (Taplin et al. 1995) and Mariotto (Mariotto et al. 2011) in their estimates of initial care costs for patients with distant disease.

We are not aware of previous studies evaluating the medical care costs for patients with recurrent lung or colorectal cancer. For patients with recurrent breast cancer, our estimates of average total annual costs differed from those reported previously. Specifically, for 765 recurrent breast cancer cases (mean age 62.5), we estimated costs before and after recurrence to be $27,038 and $57,549 (2012$U.S., data not shown), respectively. Studying 62 patients with recurrent breast cancer who had at least 12 months of follow‐up, Lamearto (Lamerato et al. 2006) reported billed charges of $12,344 before and $79,253 after recurrence (2003$U.S.). However, in addition to a much smaller cohort, this analysis included younger patients, used charges rather than costs, and did not include pharmacy charges. Karnon (Karnon et al. 2007) estimated costs in the year after a metastatic recurrence (2004£) for patients who died/experienced a subsequent event (n = 56) and for patients who remained alive with no further event (n = 36), to be £10,003 and £9,409, respectively. Stokes (Stokes et al. 2008) used SEER/Medicare claims to estimate the 10‐year costs of care for patients with recurrent breast cancer, finding that costs ranged from $11,000 to $19,183 (2004$U.S.). Even after adjusting for inflation and exchange rates, most of these other estimates are approximately 50 percent lower than our findings.

Our study begins to fill large gaps in the literature on the variation in medical care costs for patients with recurrent versus de novo metastatic disease, within and across three cancer types that comprise a sizeable proportion of the overall economic burden of cancer in the United States (Yabroff et al. 2011). The strengths of our study include the use of tumor registry data to identify cancer cases and recurrences—supplemented with a validated cancer recurrence detection and timing algorithm (Hassett et al. 2014; Ritzwoller et al. 2017). Second, we captured complete utilization and costs of medical care, both before and after the most important sentinel event in the cancer trajectory. We did not use health plan‐specific charges, costs, or payments, given that they can vary for the same service, for the same diagnosis and/or treatment, and even across regions within the Kaiser Permanente program. Instead, we implemented a standardized costing algorithm that is based on Medicare fee schedules (O'Keeffe‐Rosetti et al. 2013), thus allowing comparisons between our estimates and other published SEER‐/Medicare‐based estimates.

However, our study is not without limitations. First, we did not estimate “net” medical care costs relative to matched noncancer controls (Campbell and Ramsey 2009; Guy et al. 2013; Yabroff, Borowski, and Lipscomb 2013; Yabroff et al. 2013); however, findings from our prior work indicate that net costs (i.e., those attributable specifically to cancer) account for the majority of total costs in the year following diagnosis among de novo breast, colorectal, and lung cancer patients (Banegas et al. 2015). We did not decompose all the components driving variation in medical care costs within and between groups. The cost estimates reported in our study reflect utilization patterns of populations diagnosed with cancer between 2000 and 2011 (2012 for recurrent cancers), and thus, our estimates do not account for more recently approved, and often higher‐cost, targeted therapies. Also, our study sample was not as racially, ethnically, and geographically diverse as the U.S. population. Further, we present cost estimates from the payer or health system perspective and do not capture patient cost liabilities, which may lead to substantial financial hardship for many patients and their families (Banegas and Yabroff 2013). Assessing the financial burden of patients with recurrent cancer is largely unknown and should be a focus of future research. Lastly, our study is specific to the experience of patients receiving care from salary‐based clinicians within three KP integrated health care systems. Consistent with our previous studies related to treatments and outcomes for patients with advanced cancer (Ritzwoller et al. 2012, 2014), we strongly believe that our findings generalize to other settings. However, given that financial incentives to provide more expensive treatments are mitigated within the KP setting, the cost estimates from this study may actually be less than what one might observe in a fee‐for‐service setting.

Cost differences between de novo and recurrent cancers reveal heterogeneity in care patterns that merits further investigation. Understanding differences in costs/utilization for de novo and recurrent cancer patients is critical when developing treatment plans, evaluating factors associated with spending/quality (including assessing overuse and underuse), and studying episode‐based reimbursement models. The costs reported by this study may serve as a benchmark for stage‐specific phase‐of‐care oncology episode payment models and future cost‐effectiveness studies of treatments for advanced cancer.

Supporting information

Appendix SA1: Author Matrix.

Click here for additional data file. (1.2MB, pdf)

Figure S1: Qualifying Patients for Recurrence Cost Analysis.

Click here for additional data file. (38.5KB, doc)

Table S1: Average Total Monthly Cost Model Parameter Estimates by Cancer Site.

Click here for additional data file. (16.1KB, docx)

Acknowledgments

Joint Acknowledgment/Disclosure Statement: This work was supported by a grant from the National Cancer Institute (R01 CA172143 DPR/MJH), with additional support from NCI (U2 C171524 to the Cancer Research Network, Lawrence Kushi, PI), R01 CA10527, U01 CA195565; The American Society of Clinical Oncology (Career Development Award) to MJH.

Disclosures: None.

Disclaimer: None.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Appendix SA1: Author Matrix.

Click here for additional data file. (1.2MB, pdf)

Figure S1: Qualifying Patients for Recurrence Cost Analysis.

Click here for additional data file. (38.5KB, doc)

Table S1: Average Total Monthly Cost Model Parameter Estimates by Cancer Site.

Click here for additional data file. (16.1KB, docx)

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