P

Original Research

Prevalence of Prostate Cancer in Patients WithChronic Spinal Cord InjuryNikhil Patel, MD, Kenneth Ngo, MD, James Hastings, PhD, Nicholas Ketchum, MD,

Farhad Sepahpanah, MD

Objective: To determine the prevalence of prostate cancer in patients with chronic spinalcord injury (SCI), with regard to the duration, level, and severity of injury.Design: Retrospective chart review study.Setting: Inpatient and outpatient Veterans Affairs spinal cord unit.

articipants: The electronic medical records of 350 veterans with chronic SCI and 344veterans without SCI as a control group were reviewed.Main Outcome Measure: Prevalence of prostate cancer in patients with chronic SCIwith regard to the duration, level, and severity of injury.Results: Of 350 veterans with chronic SCI, 7 individuals (2%) had prostate cancer. Incomparison, of 344 age-matched veterans without SCI, 18 (5.2%) had prostate cancer. InSCI group with prostate cancer, 2 patients had motor complete injury (American SpinalCord Injury Association Impairment Scale [AIS] A and B), and 5 patients had motorincomplete injury (AIS C, D, and E). Patients with SCI and with prostate cancer were slightlyolder (mean [SD] age, 72.14 � 8.25 years) than the control group (mean [SD] age, 69.83 �8.79 years) with cancer.Conclusion: Findings from this study indicate a lower prevalence of prostate canceramong veterans with chronic SCI in comparison with age-matched veterans without SCI.Given the small number of patients with SCI and with prostate cancer in this study, we didnot find any statistically significant correlation between the prevalence of prostate cancerand the level, duration, and severity of injury.

PM R 2011;3:633-636

INTRODUCTION

Every year, more than 10,000 persons in the United States incur a spinal cord injury (SCI),with an overall prevalence of 350,000 cases [1]. Approximately 80% of patients with SCI aremen [1]. With advances in technology and routine yearly checkups of individuals with SCI,the life expectancy for these patients has been significantly improved and approaches that ofthe general population [2].

Prostate cancer is the most common cancer, and prostate enlargement is the mostcommon benign tumor in men [3]. Age is a significant factor in developing prostate cancerin men. In fact, based on reports from the Prostate Cancer Foundation, more than 65% of allprostate cancers are diagnosed in men over the age of 65 years [3]. The average age atdiagnosis of prostate cancer in the United States is 69 years [3]. With the aging of the SCIpopulation [2], one may expect to see larger numbers of patients with SCI with prostatecancer later in their life. However, results some of the previous studies show lowerprevalence of prostate cancer in the patients with more severe SCI. [4,5]

Results of animal studies indicate the important role of hormonal and neurologic factorsin the growth of the prostate gland [6-8]. This relationship between the neurologic andendocrine systems with the prostate gland in human beings is not well understood.Furthermore, despite the increasing number of individuals with SCI who are living longer,little is known about the effect of SCI on the prostate gland [9].

At the Veterans Affairs (VA) medical centers, all veterans with the diagnosis of SCI

undergo routine comprehensive checkups once a year. Measuring serum prostate specific

PM&R © 2011 by the American Academy of Physical Me1934-1482/11/$36.00

Printed in U.S.A. D

N.P. Department of Physical Medicine andRehabilitation, Medical College of Wisconsin,Milwaukee, WIDisclosure: nothing to disclose

K.N. Department of Physical Medicine andRehabilitation, Medical College of Wisconsin,Milwaukee, WIDisclosure: nothing to disclose

J.H. Spinal Cord Injury Service, Clement J.Zablocki VA Medical Center, Milwaukee, WIDisclosure: nothing to disclose

N.K. Department of Physical Medicine andRehabilitation, Medical College of Wisconsin,Milwaukee, WIDisclosure: nothing to disclose

F.S. Spinal Cord Injury Services, Clement J.Zablocki VA Medical Center, 5000 W NationalAve, Milwaukee, WI 53295. Address corre-spondence to: F.S.; e-mail: fsepahpa@mcw.eduDisclosure: nothing to disclose

Disclosure Key can be found on the Table ofContents and at www.pmrjournal.org

Submitted for publication June 15, 2010;accepted April 22, 2011.

dicine and RehabilitationVol. 3, 633-636, July 2011

OI: 10.1016/j.pmrj.2011.04.024633

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634 Patel et al PROSTATE CANCER IN PATIENTS WITH CHRONIC SCI

antigen (PSA) is part of the routine checkup for veteransolder than 40 years. Those veterans with PSA higher than 4ng/mLare referred to the urologist for further assessment and apossible prostate biopsy. The diagnosis of prostate cancer ismade based merely on the pathologic interpretation of theprostate biopsy. Our goal in this study was to determine theprevalence of prostate cancer in veterans with chronic SCIand its relationship to the duration, level, and severity of theSCI. We defined chronic SCI as injuries of more than 2 years’duration. The results were compared with an age-matchedsample of veterans without SCI who came to the same med-ical center for outpatient visits.

METHODS

This study was approved by our hospital’s institutional re-view board. In our SCI unit, we provide care for 445 maleveterans with a diagnosis of SCI who come to our facility oncea year for an annual evaluation. The annual evaluation is acomprehensive history and physical examination designed tooptimize the patient’s health maintenance and well-being.Many of our veterans are admitted to the hospital for theseevaluations because of the extent of the testing, the timerequired for travel to and from the clinic, and the socioeco-nomic limitations of this cohort. Evaluations are offeredannually to the patients. Because of patients’ preferences,scheduling conflicts, and other factors, the interval betweenevaluations frequently exceeds 1 year. By using a locallymaintained patient registry, we obtained a list of all thepatients who had completed an annual evaluation during2008 and 2009. The patients were evaluated and examinedby VA SCI staff physiatrists during their annual checkup, anddocumentation of the encounter was thoroughly reviewed inthis study.

Subjects and Data Collection

This study’s population included all individuals with SCIwho were registered at the SCI unit in the Zablocki VAMedical Center (n � 445). We selected all male veterans withhronic SCI (at least 2 years from the time of injury), aged 40ears or older, and who had a serum PSA measured at their008 and 2009 annual checkups. We excluded veterans whoad a PSA value of �4 ng/mL and/or a diagnosis of prostateancer before their SCI and referred to us for treatment, asell as veterans with acute prostatitis or urinary tract infec-

ion (UTI). We also excluded veterans who had been diag-osed with prostate cancer in other facilities and who hadome to the Zablocki VA Medical Center for treatment. Of the45 individuals screened, 90 veterans were excluded becausef their age (less than 40 years), new injury (less than 2 years)r because they had never had their PSA checked. We also

xcluded 5 veterans with SCI who developed SCI secondary

o their prostate cancer. The records of the remaining 350eterans were reviewed, and the data collected included age,ear of injury, level of SCI, severity of injury based on themerican Spinal Cord Injury Association Impairment Scale

AIS), method of bladder management, both the latest andighest PSAs in the measurement period, and whether thereas a post-SCI diagnosis of prostate cancer.With a computer-generated, randomized number, we se-

ected 344 veterans from among more than 18,000 veteransithout SCI who had come to the Zablocki VA Medicalenter for their outpatient visits during the same time period

2008-2009). To have a near-perfect age-matched controlroup in veterans without SCI, we divided our SCI andeterans without SCI to 10-year age brackets starting at age0 years. We chose the same number of cases in each bracketor the SCI and control groups. From our control group, wexcluded 11 able-bodied veterans who had been diagnosedith prostate cancer in other hospitals and sent to our facility

or further treatment. Because our medical center is a referralenter, excluding these 11 referral patients with prostateancer was essential to prevent the bias result of significantumber of prostate cancer referrals from other places.

All statistical analyses were performed by using SPSSoftware (SPSS Inc, Chicago, IL). The Pearson �2 test was

used to compare differences within and between the SCI andcontrol groups on categorical data. Differences in the contin-uous variables were evaluated by using t-tests, one-way anal-ysis of variance, and Pearson correlation coefficients. Statis-tical significance was accepted with traditional probabilitylevels (P � .05).

RESULTS

The electronic chart records of 350 qualified veterans withSCI were reviewed. The average (�SD) age in this group was59.53 � 8.98 years, with an average (�SD) length of SCI22.02 � 14.12 years. Regarding the severity of injury in theSCI group, 131 veterans were classified as AIS A, 48 as AIS B,41 as AIS C, 122 as AIS D, and 8 as AIS E (Table 1).

We identified 7 veterans (2%) with prostate cancer in thegroup with SCI (average [�SD] age, 72.14 � 8.25 years).The average (�SD) age for patients with SCI without prostatecancer was 59.28 � 8.82 years (Table 2). In the SCI group,age was significantly related to the occurrence of cancer(�2 �13.76, df � 3, P � .003).

In the SCI group, 179 veterans (51.14%) had a completemotor injury (AIS A and B). Among them, only 2 veterans hadprostate cancer (1.1%). There were 171 veterans (48.85%) inSCI group who had an incomplete motor injury (AIS C, D,and E). We found 5 veterans with prostate cancer in thisgroup (2.9%) (Table 2). Although, in the SCI group, wefound more subjects with prostate cancer in those withincomplete injuries, given the very small sample size (7

prostate cancer cases in total), there was not a statistically

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635PM&R Vol. 3, Iss. 7, 2011

significant difference between prostate cancer in patientswith complete versus incomplete injuries (�2 � 1.475, df �1, P � not significant). Perhaps for the same reason, theprevalence of prostate cancer in the SCI group was not foundto be significantly related to the duration or level of injury inthis small sample.

The average (SD) age in the control group was 59.53 �9.04 years). We found 18 veterans (5.2%) with prostatecancer (average [SD] age, 69.83 � 9.03 years) in the controlgroup (Table 2). There were significantly more prostate can-cers in the control group than in the SCI group: (�2 � 5.22,df � 1, P � .022). Similar to the SCI group, the prevalence of

rostate cancer was positively related to the age in controlroup (�2 � 29.50, df � 3, P � .001).

The average (SD) time since the diagnosis of prostatecancer in the control group was 2.28 � 3.24 years. None ofour veterans with prostate cancer in the control group werediagnosed more than 6 years before our study. There was nostatistically significant age difference between the SCI groupand control group (t approximately 0.01, P � .993). All 18prostate cancers in the control group occurred in individuals60 years of age or older (�2 � 29.50, df � 3, P � .001).

DISCUSSION

The main goal of this study was to determine the prevalence

Table 1. Patient population stratified by level of spinal cordinjury, AIS category, and bladder function

VariableNo. of Patients

(N � 350) % of Patients

Level of injuryCervical 169 48Upper thoracic 66 19Lower thoracic 83 24Lumbar and sacral 32 9

AISA 131 37B 48 14C 41 12D 122 35E 8 2

Bladder managementNormal 81 23Foley catheter 112 32Intermittent straightcatheter

77 22

Suprapubiccatheter

34 10

Condom catheter 38 11Urostomy 2 0.6Ilial conduit 4 1.1Indiana pouch 2 0.6

AIS � American Spinal Cord Injury Association Impairment Scale.Note: AIS categories A and B denote motor complete injury, whereas AIS

categories C, D, and E denote motor incomplete injury.

of prostate cancer among patients with SCI. The second goal

was to define any relationships between the severity of injury,duration, and the level of injury with prostate cancer. Asample of patients with SCI and over age 40 years wascompared with a computer-picked, randomly selected, age-matched sample of veterans without SCI who came to thesame VA medical center for their outpatient visits. The resultsshowed that the prevalence of prostate cancer in the non-SCIcontrol group was significantly higher than in the SCI group.In both groups, as was expected, there was a direct correla-tion between the prevalence of prostate cancer and veterans’age (ie, older patients were more likely to have prostatecancer). There were fewer prostate cancers in the SCI groupwith complete motor injuries (AIS A and B) than in those whohad incomplete motor injuries (AIS C, D, and E). Also, thepatients with both SCI and prostate cancer were slightly olderthan patients without SCI and with prostate cancer. The latterfinding, derived from very small samples, did not achievestatistical significance.

Similar results were found in a small group of veteranswith SCI in 2001 [4]. With that study, the lowest rate ofprostate cancer occurred in veterans with complete SCIs at orabove the T10 level of injury. Veterans with incomplete SCIsor injuries at T11 and below had higher rates of prostatecancer [4].

To determine the effect of the level of injury on theprevalence of prostate cancer, the SCI group was divided intocervical, upper thoracic (T1-T6), lower thoracic (T7-T12),and lumbar–sacral subgroups. In our study, there was nostatistically significant correlation between the prevalence ofprostate cancer and the level of injury, although the smallsample size may have limited the ability to detect suchdifferences.

It is not clear why the prevalence of prostate cancer islower in patients with SCI. Neurologic factors such as inner-vations of the prostate gland can change the size and activityof the prostate in patients with SCI [7]. In animal studies,denervation of the prostate gland resulted in cellular mor-phology, growth, and function changes [8]. Besides the neu-rologic factors, hormonal factors also can play an importantrole. Testosterone is the most important male hormone thatcan directly affect the prostate gland [9-11]. The effect oftestosterone in hyperplasia of the prostate gland has been

Table 2. Study population stratified by severity or absence ofspinal cord injury

Population

CompleteSCI

Patients

IncompleteSCI

PatientsNon-SCIControls

No. of subjects 179 171 344Mean (SD) age, y 58.9 � 8.93 60.8 � 9.07 59.53 � 9.04No. with prostatecancer

2 (1.1%) 5 (2.94%) 18 (5.2%)

SCI � spinal cord injury.Note: SCI is assessed according to the American Spinal Cord Injury

Association Impairment Scale (AIS).

636 Patel et al PROSTATE CANCER IN PATIENTS WITH CHRONIC SCI

documented for many years. It has been shown that testos-terone can expedite prostate cancer cell replication [10].Without testosterone, most prostate cancer cells grow at amuch slower pace. Multiple studies of patients with SCI haveshown much lower levels of serum testosterone in patientswith complete SCI [10,11]. Perhaps the lower serum testos-terone in patients with SCI reduces the prevalence of prostatecancer in these patients [12]. There is no evidence thattestosterone can cause prostate cancer, but a lack of testos-terone may slow down progress in the growth of cancer cellsand thereby reduce the prevalence of prostate cancer in theSCI population. In this study, the average age for the smallsample of patients with SCI and with prostate cancer washigher than the non-SCI group with prostate cancer (al-though the difference was not statistically significant). Lowerserum testosterone in patients with SCI [13,14], especiallythose with complete SCI, may explain why the prostatecancer cells that grow in the absence of testosterone willpresent in the older patients with SCI [13-15]. A future studywith a larger sample size is needed to determine this correla-tion.

Study Limitations

The retrospective nature of this study is its greatest limitation.The ideal study design would have been to calculate theprevalence of prostate cancer in patients with chronic SCI,starting from 2 years after the SCI, and compare these pa-tients with an age-matched control group who were cancerfree at the age when their matched case patients developedSCI. The second limitation of this study was the small num-ber of patients with prostate cancer in the SCI group. Al-though we included 350 patients with SCI in this study, therewere only 7 patients who had prostate cancer. Such a smallsample size limits the statistical power needed to identifysignificant differences in some of the comparisons made inthis study. A much larger, prospective study to examine therelationship of serum testosterone and prostate cancer withthe level and severity of injury might begin to clarify some ofthe basic questions regarding the interactions among theendocrine system, the spinal cord, and the prostate gland.

CONCLUSION

Although findings from this study indicate a lower preva-

lence of prostate cancer in patients with SCI, especially in

those with complete injury, there is a need for largerprospective studies. In searching for the answer to thepossibility of lower prevalence of prostate cancer in pa-tients with chronic SCI, we believe that there should bespecial attention given to the testosterone deficiency inpatients with chronic SCI.

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