What Does It Mean When Your Psa Goes From .3 to .4 After Radiation

• Journal List
• Fed Pract
• v.36(Suppl 1); 2019 Feb
• PMC6411359

Fed Pract. 2019 February; 36(Suppl ane): S16–S21.

Prostate Cancer Surveillance After Radiation Therapy in a National Delivery System

Abstract

Guideline cyclopedia with PSA surveillance amid veterans treated with definitive radiation therapy was generally loftier, but opportunities may exist to meliorate surveillance among select groups.

Guidelines recommend prostate-specific antigen (PSA) surveillance among men treated with definitive radiation therapy (RT) for prostate cancer. Specifically, the National Comprehensive Cancer Network recommends testing every vi to 12 months for 5 years and annually thereafter (with no specific stopping flow specified), while the American Urology Association recommends testing for at least 10 years, with the frequency to exist determined by the risk of relapse and patient preferences for monitoring.1,2 Salve treatments exist for men with localized recurrence identified early through PSA testing, so adherence to follow-up guidelines is important for quality prostate cancer survivorship care.1,two

Notwithstanding, few studies focus on adherence to PSA surveillance following radiation therapy. Posttreatment surveillance among surgical patients is generally loftier, but sociodemographic disparities be. Racial and indigenous minorities and unmarried men are less likely to undergo guideline concordant surveillance than is the full general population, potentially preventing constructive salvage therapy.3,4 A recent Department of Veterans Affairs (VA) written report on posttreatment surveillance included radiation therapy patients merely did non examine the bear on of younger age, concurrent androgen deprivation therapy (ADT), or treatment facility (ie, diagnosed and treated at the aforementioned vs different facilities, with the latter including a separate VA facility or the community) on surveillance patterns.5 The latter is particularly relevant given increasing efforts to coordinate care exterior the VA delivery system supported by the 2018 VA Maintaining Systems and Strengthening Integrated Outside Networks (MISSION) Act. Furthermore, these patient, treatment, and delivery system factors may each uniquely contribute to whether patients receive guideline-recommended PSA surveillance later on prostate cancer treatment.

For these reasons, we conducted a study to better understand determinants of adherence to guideline-recommended PSA surveillance among veterans undergoing definitive radiation therapy with or without concurrent ADT. Our report uniquely included both elderly and non-elderly patients likewise as investigated relationships betwixt treatment at or abroad from the diagnosing facility. Although we found loftier overall levels of adherence to PSA surveillance, our findings practice offering insights into determinants associated with worse adherence and provide opportunities to ameliorate prostate cancer survivorship care later RT.

METHODS

This report population included men with biopsy-proven nonmetastatic incident prostate cancer diagnosed between January 2005 and December 2008, with follow-up through 2012, identified using the VA Central Cancer Registry. We included men who underwent definitive RT with or without concurrent ADT injections, determined using the VA chemist's shop files. We excluded men with a prior diagnosis of prostate or other malignancy (given the presence of other malignancies might touch on life expectancy and surveillance patterns), hospice enrollment within 30 days, diagnosis at autopsy, and those treated with radical prostatectomy. We extracted cancer registry data, including biopsy Gleason score, pretreatment PSA level, clinical tumor phase, and whether RT was delivered at the patient's diagnosing facility. For the latter, we used information on radiations location coded past the tumor registrar. We also collected demographic information, including historic period at diagnosis, race, ethnicity, marital status, and ZIP code. We used diagnosis codes to make up one's mind Charlson comorbidity scores similar to prior studies.6–viii

Primary Outcome

The master upshot was receipt of guideline concordant annual PSA surveillance in the initial 5 years following RT. Nosotros used laboratory files within the VA Corporate Data Warehouse to identify the date and value for each PSA test afterwards RT for the entire cohort. Specifically, nosotros defined the surveillance period as threescore days after initiation of RT through December 31, 2012. We defined guideline concordance every bit receiving at to the lowest degree one PSA exam for each 12-month period after RT.

Statistical Assay

We used descriptive statistics to characterize our accomplice of veterans with prostate cancer treated with RT with or without concurrent ADT. To handle missing information, we performed multiple imputation, generating x imputations using all baseline clinical and demographic variables, year of diagnosis, and the regional VA network (ie, the Veterans Integrated Services Network [VISN]) for each patient.

Side by side, we calculated the almanac guideline concordance charge per unit for each year of follow-up for each patient, for the overall accomplice, every bit well as by historic period, race/ethnicity, and concurrent ADT use. Nosotros examined bivariable relationships betwixt guideline concordance and baseline demographic, clinical, and delivery system factors, including yr of diagnosis and whether patients were treated at the diagnosing facility, using multilevel logistic regression modeling to business relationship for clustering at the patient level.

Analyses were performed using Stata Version 15 (College Station, TX). We considered a ii-sided P value of < .05 as statistically pregnant. This written report was canonical by the VA Ann Arbor Health Care Organization Institution Review Lath.

RESULTS

We evaluated annual PSA surveillance for 15,538 men treated with RT with or without concurrent ADT (Table one). Most men were white (70%), with 29% black and 3% Hispanic. Half (51%) the men were married, and the minority lived in rural areas (16%). The majority of men had screen-detected prostate cancer that was Gleason score ≥ 7, and with PSA ≤ 10 ng/mL. Most men were treated without concurrent ADT (sixty%), while those with concurrent ADT tended to take more ambitious disease factors (ie, higher PSA and Gleason score). Approximately one-half (52%) of veterans with prostate cancer received RT away from their diagnosing facility.

TABLE i

Baseline Characteristics of Veterans With Prostate Cancer Treated With Radiation Therapy

Characteristics	Overall (N = 15,538)	Radiations (North = 9,380)	Radiations + ADT (North = half dozen,158)
Age at diagnosis, mean (SD), y	65.76 (seven.v)	65.12 (7.3)	66.73 (7.8)
Race, No. (%)
White	10,929 (70.three)	half-dozen,664 (71.0)	4,265 (69.3)
Blackness	4,442 (28.6)	two,617 (27.nine)	i,825 (29.vi)
Other	167 (1.ane)	99 (1.i)	68 (1.1)
Ethnicity, No. (%)
Non Hispanic	15,023 (96.vii)	ix,054 (96.5)	v,969 (96.nine)
Hispanic	515 (3.3)	326 (three.5)	189 (3.one)
Married, No. (%)
Not married	7,597 (48.9)	iv,563 (48.vi)	3,034 (49.3)
Married	vii,941 (51.one)	4,817 (51.4)	three,124 (50.vii)
Rurality, No. (%)
Urban	thirteen,131 (84.5)	seven,866 (83.9)	v,265 (85.v)
Rural	2,407 (15.5)	1,514 (16.1)	893 (fourteen.5)
Charlson Score, No. (%)
0	6,770 (43.6)	iv,149 (44.2)	2,621 (42.6)
1	4,371 (28.i)	2,632 (28.1)	1,739 (28.ii)
≥ 2	4,397 (28.3)	2,599 (27.7)	one,798 (29.2)
Gleason Score, No. (%)
6	six,772 (43.6)	five,610 (59.8)	1,162 (18.9)
7	6,081 (39.1)	3,314 (35.3)	2,767 (44.9)
8–10	2,685 (17.three)	456 (4.9)	2,229 (36.2)
PSA, No. (%)
≤ x	xi,592 (74.6)	8,044 (85.7)	3,548 (57.6)
> 10 to ≤ xx	two,577 (16.6)	1,094 (eleven.7)	i,483 (24.i)
> 20	1,369 (viii.8)	242 (2.6)	1,127 (xviii.3)
Clinical T Stage, No. (%)
T1c-T2a	12,576 (fourscore.9)	8,256 (88.0)	4,320 (lxx.1)
T2b	732 (four.7)	328 (3.five)	404 (6.six)
≥ T2c	2,230 (xiv.iv)	796 (8.5)	i,434 (23.3)
Treatment, No. (%)
Radiation	9,380 (60.4)	9,380 (100)	0 (0)
Radiation + ADT	6,158 (39.vi)	0 (0)	6,158 (100)
Treatment facility, No. (%)
Same every bit diagnosing facility	7,480 (48.2)	four,897 (52.two)	iii,153 (51.2)
Dissimilar facility	viii,050 (51.viii)	4,483 (47.8)	3,005 (48.8)

On unadjusted analysis, annual guideline concordance was less mutual among patients who were at the extremes of age, white, had Gleason vi affliction, PSA ≤ 10 ng/mL, did not receive concurrent ADT, and were treated away from their diagnosing facility (P < .05) (data not shown). Nosotros did find slight differences in patient characteristics based on whether patients were treated at their diagnosing facility (Tabular array ii). Patients treated at facilities other than where they were diagnosed were more than rural, white, and married, with slight differences in baseline PSA and Gleason scores but similar use of radiation monotherapy and concurrent ADT.

Table 2

Baseline Characteristics of Veterans With Prostate Cancer by Treatment Facility

Characteristics	Radiation Handling Location		P Value
	Aforementioned Facility equally Diagnosis (N = 7,488)	Different Facility Than Diagnosis (Northward = 8,050)
Age at diagnosis, mean (SD), y	65.31 (7.half dozen)	66.18 (7.four)
Race, No. (%)			< .001
White	4,525 (threescore.5)	6,404 (79.5)
Black	2,900 (38.7)	one,542 (nineteen.2)
Other	63 (0.8)	104 (1.3)
Ethnicity, No. (%)			< .001
Not Hispanic	7,179 (95.ix)	7,844 (97.4)
Hispanic	309 (4.1)	206 (two.half dozen)
Married, No. (%)			< .001
Not married	iii,967 (53.0)	3,630 (45.one)
Married	iii,521 (47.0)	4,420 (54.9)
Rurality, No. (%)			< .001
Urban	half-dozen,635 (88.half-dozen)	six,496 (80.seven)
Rural	853 (11.four)	1,554 (19.3)
Charlson Score, No. (%)			< .001
0	3,145 (42.0)	iii,625 (45.1)
one	2,073 (27.7)	ii,298 (28.5)
≥ two	2,270 (30.three)	two,127 (26.four)
Gleason Score, No. (%)			.006
6	3,164 (42.3)	3,608 (44.8)
7	two,997 (xl.0)	three,084 (38.three)
8–10	one,327 (17.seven)	1,358 (sixteen.9)
PSA, No. (%)			< .001
≤ 10	five,500 (73.four)	vi,092 (75.7)
> 10 to ≤ twenty	1,248 (16.vii)	one,329 (16.5)
> xx	740 (9.9)	629 (vii.8)
Clinical T Phase, No. (%)			.930
T1c-T2a	6,062 (81.0)	half dozen,514 (80.9)
T2b	348 (4.6)	384 (iv.eight)
≥ T2c	i,078 (xiv.4)	ane,152 (14.three)
Treatment, No. (%)			.220
Radiation	4,483 (59.9)	4,897 (60.8)
Radiations + ADT	three,005 (40.ane)	3,153 (39.2)

Overall, we found annual guideline concordance was initially very high, though declined slightly over the study period. For instance, guideline cyclopedia dropped from 96% in year 1 to 85% in year 5, with an boilerplate patient-level guideline cyclopedia of 91% during the study menstruum. We found minimal differences in annual surveillance subsequently RT by race/ethnicity (Figure ane).

Annual Guideline Concordance for PSA Surveillance Among 15,538 Patients After RT in a National Commitment System According to Race and Ethnicity

Abbreviations: PSA, prostate-specific antigen; RT, radiations therapy.

On multilevel multivariable analysis to adjust for clustering at the patient level, we found that race and PSA level were no longer significant predictors of almanac surveillance (Table 3). However, the following factors remained significant determinants of lower guideline concordance: extremes of historic period, Gleason vi affliction, RT without concurrent ADT (adjusted odds ratio [aOR] 1.00 radiation therapy alone vs ane.84 radiation therapy with ADT, P < .01; 95% CI, 1.62–two.09), and treatment at a different facility from where one was diagnosed (aOR ane.00 different facility vs one.lxx aforementioned facility, P < .01; 95% CI, i.53–one.90). The post-obit factors became significant on multivariable analysis: existence nonmarried (aOR 1.00 nonmarried vs one.12 married, P = .03; 95% CI, one.01–one.25), and urban residence (aOR 1.00 urban vs 1.twenty rural, P = .02; 95% CI, 1.03–i.39). Men treated with RT with concurrent ADT were more likely to have greater annual surveillance whether they were treated within or outside of their diagnosing facility (Effigy ii).

Model Predicted Almanac PSA Guideline Cyclopedia by Handling Location and Receipt of Concurrent ADT

Abbreviations: ADT, androgen impecuniousness therapy; PSA, prostate-specific antigen; RT, radiation therapy.

TABLE iii

Determinants of Almanac PSA Surveillance After RT on Multilevel Multivariable Assay (Clustering at Patient Level)

Characteristics	Adapted Odds Ratio	P Value	95% CI
			Lower	Upper
Historic period	1.25	< .01	ane.13	i.38
Historic period2	0.998	< .01	0.997	0.999
Race
White	1.00
Black	0.99	.82	0.87	1.12
Other	1.61	.09	0.93	2.79
Ethnicity
Non-Hispanic	1.00
Hispanic	1.19	.26	0.88	one.60
Marital Status
Nonmarried	i.00
Married	one.12	.03	ane.01	1.25
Rurality
Urban	1.00
Rural	i.xx	.02	i.03	1.39
Charlson Score
0	1.00
1	ane.01	.85	0.89	ane.15
≥ ii	1.01	.91	0.89	1.xiv
Gleason Score
6	i.00
seven	one.04	.55	0.92	1.17
8–10	1.22	.03	i.02	1.46
PSA at diagnosis
≤ 10
> x & ≤ 20	0.88	.09	0.76	1.02
> 20	0.86	.xiv	0.70	1.05
Clinical phase
≤ T2a	1.00
T2b	1.04	.74	0.81	one.35
≥ T2c	0.99	.89	0.84	ane.16
Yr (vs i)
2	0.54	< .01	0.48	0.61
3	0.31	< .01	0.28	0.35
4	0.xix	< .01	0.17	0.22
five	0.14	< .01	0.12	0.16
Treatment (vs RT)
RT + ADT	1.84	< .01	1.62	2.09
Treatment location
Different facility	1.00
Same facility	1.70	< .01	i.53	1.90

DISCUSSION

We investigated adherence to guideline-recommended annual surveillance PSA testing in a national cohort of veterans treated with definitive RT for prostate cancer. We found guideline cyclopedia was initially high and decreased slightly over fourth dimension. Nosotros likewise establish guideline concordance with PSA surveillance varied based on a number of clinical and delivery system factors, including marital condition, rurality, receipt of concurrent ADT, every bit well as whether the veteran was treated at his diagnosing facility. Taken together, these overall results are promising, nonetheless, as well point to unique considerations for some patient groups and potentially those treated in the community.

Our finding of lower guideline cyclopedia among nonmarried patients is consistent with prior enquiry, including our study of patients undergoing surgery for prostate cancer.4 Addressing surveillance in this population is important, equally they may have less social back up than do their married counterparts. We also constitute surveillance was lower at the extremes of age, which may exist advisable in elderly patients with limited life expectancy but is concerning for younger men with low competing bloodshed risks.7 Future work should explore whether younger patients experience barriers to care, including employment challenges, as these men are at greatest take chances of cancer progression if recurrence goes undetected.

Although rural patients are less probable to undergo definitive prostate cancer handling, possibly reflecting barriers to intendance, in our study, surveillance was actually college among this population than that for urban patients.9 This could reflect the VA'due south success in connecting rural patients to appropriate services despite travel distances to maintain quality of cancer care.10 Given almanac PSA surveillance is relatively exceptional and not particularly resource intensive, these high surveillance rates might non apply to patients with cancers who need more frequent survivorship care, such as those with head and neck cancer. Future work should examine why surveillance rates among urban patients might be slightly lower, as living in a metropolitan area does not equate to the absence of barriers to survivorship intendance, peculiarly for veterans who may non be able to have time off from piece of work or take transportation barriers.

We plant guideline concordance was higher among patients with higher Gleason scores, which is of import given their college likelihood of failure. However, low- and intermediate-risk patients also are at take chances for handling failure, and then annual PSA surveillance should be optimized in this population unless hereafter studies support the safety and feasibility of less frequent surveillance.10–13 Our finding of increased surveillance in patients who receive concurrent ADT may relate to the increased frequency of survivorship care given the need for injections, often every 3 to six months. Hereafter studies might examine whether surveillance decreases in this population in one case they complete their short or long-term ADT, typically given for a maximum of 3 years.

A especially relevant finding given recent VA policy changes includes lower guideline cyclopedia for patients receiving RT at a different facility than where they were diagnosed. Ane possible explanation is that a proportion of patients treated exterior of their dwelling facilities employ Medicare or individual insurance and may have surveillance performed outside of the VA, which would non take been captured in our study.xiv However, information technology remains plausible that in that location are challenges related to coordination and fragmentation of survivorship intendance for veterans who receive care at separate VA facilities or receive their initial treatment in the community.15 Future studies can help quantify how much this difference is driven by diagnosis and treatment at divide VA sites vs treatment outside of the VA, as dissimilar strategies might be necessary to amend surveillance in these 2 populations. Moreover, electronic health tape-based tracking has been proposed as a strategy to identify patients who have non received guideline concordant PSA surveillance.14 This strategy may assistance increase guideline cyclopedia regardless of initial treatment location if VA survivorship care is intended.

Although our study examined receipt of PSA testing, information technology did non examine whether patients are physically seen dorsum in radiation oncology clinics, or whether their PSAs take been reviewed by radiation oncology providers. Although many surgical patients render to primary care providers for PSA surveillance, surveillance after RT is more than circuitous and likely best managed in the initial years by radiation oncologists. Unlike the postoperative setting in which the definition of PSA failure is straightforward at > 0.two ng/mL, the definition of treatment failure after RT is more complicated every bit described below.

For patients who did not receive concurrent ADT, failure is defined as a PSA nadir + ii ng/mL, which get-go requires establishing the nadir using the first few postradiation PSA values.15 It becomes even more complex in the setting of ADT as it causes PSA suppression even in the absence of RT due to testosterone suppression.two At the conclusion of ADT (short term 4–6 months or long term eighteen–36 months), the PSA may rise as testosterone recovers.xv,16 This is non necessarily indicative of treatment failure, as some normal PSA-producing prostatic tissue may remain afterwards treatment. Given these complexities, ongoing survivorship care with radiation oncology is recommended at least in the brusk term.

Physical visits are a challenge for some patients undergoing prostate cancer surveillance after treatment. Therefore, exploring the condom and feasibility of automated PSA tracking15 and strategies for increasing utilization of telemedicine, including clinical video telehealth appointments that are already used for survivorship and other urologic care in a number of VA clinics, represents opportunities to systematically provide highest quality survivorship intendance in VA.17,xviii

CONCLUSION

Well-nigh veterans receive guideline concordant PSA surveillance after RT for prostate cancer. Nonetheless, at the offset of treatment, providers should screen veterans for risk factors for loss to follow-up (eg, care at a unlike or not-VA facility), discuss geographic, financial, and other barriers, and plan to leverage existing VA resources (eg, travel support) to proceed to attain high-quality PSA surveillance and survivorship care. Future research should investigate means to take advantage of the VA'due south robust electronic health record arrangement and telemedicine infrastructure to farther optimize prostate cancer survivorship care and PSA surveillance particularly among vulnerable patient groups and those treated outside of their diagnosing facility.

Acknowledgments

Funding Sources: VA HSR&D Career Development Award: ii (CDA 12–171) and NCI R37 R37CA222885 (TAS).

Footnotes

Author disclosures

The authors written report no bodily or potential conflicts of interest with regard to this commodity.

Disclaimer

The opinions expressed herein are those of the authors and practise not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the United states Government, or any of its agencies.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411359/