We found that a considerable proportion of men with benign prostate biopsies after suspicious screening tests reported a negative psychological impact at 6 and 12 months, which extends our previous work showing a negative psychological impact at 6 weeks. Men with benign prostate biopsies reported substantial thinking and worrying about prostate cancer, even after the benign biopsy. In addition there appeared to be associated psychological, socio-behavioral, and medical utilization implications, demonstrating that the impact was an important one. Men in the biopsy group were more likely than men in the normal PSA group to report talking with their wife or significant other about prostate cancer, thinking their wife or significant other was worried about prostate cancer, searching on the Internet about prostate cancer, visiting the urologist, and undergoing additional PSA tests and prostate biopsies.
Investigators from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), have described the medical and nonmedical costs associated with false-positive prostate cancer screens.13
The PLCO trial found that men with false-positive prostate cancer screening results were nearly twice as likely not to return for further prostate cancer screening, compared with men with normal prostate cancers screening results.14
Our survey contrasted with this finding; the vast majority of men in our study reported being committed to having subsequent screening tests. In fact, our medical record review showed fully 71% of men in the biopsy group had at least 1 more screening PSA test in the subsequent year. The differences in the findings between our study and the PLCO substudy may be related to study design; the PLCO study was a population based screening trial, whereas our study was a nonrandomized, comparative study that recruited men from primary care physician offices. Although our study population and methodology differed, our findings are consistent with those of Schwartz et al.,15
who found that the public is enthusiastic about cancer screening, and the commitment is not dampened by false-positive test results. The finding that about 1-third of men in our biopsy group had between 2 and 4 additional PSA tests and 15% had another prostate biopsy within the year suggests that physicians and patients do not view the initial benign biopsy result as entirely reassuring, and physicians continue closely monitoring these men. It is noteworthy that the biopsied men were regular patients of urologists over the year of follow-up; 71% had seen an urologist at least once and 38% had 2 or more urology visits. This ongoing surveillance and the possibility of a false negative biopsy may help propagate the anxiety we documented among these men.
Concern about false-negative biopsy results is fairly unique to prostate cancer screening. In addition to lower specificity (therefore more false positives) than breast and colorectal cancer screening,1,16,17
the follow-up test, transrectal ultrasound-guided biopsy, involves random sampling of the prostate gland (in addition to targeted biopsies of suspicious areas), causing mounting concerns about false-negative biopsies.18
Whereas a benign biopsy in response to an abnormal mammogram is fairly reassuring (because the abnormal area of the breast has been visualized and biopsied), the elevated screening PSA, a blood test, simply represents a general indictment of the prostate gland, and, because of the poor negative predictive value of the random biopsy, at least 10% of men with a benign biopsy result will have prostate cancer detected on a subsequent biopsy.19
Therefore, urologists are urged to perform repeat sets of biopsies20
in men who have suspicious screening tests and initially benign biopsies.
The clinical significance of an elusive prostate cancer detected subsequent to a series of benign prostate biopsies has been questioned.21
Djavan and colleagues prospectively examined the biochemical and pathological features of cancer detected on biopsies 1, 2, 3, and 4, as well as the biopsy-related morbidity. The investigators found that prostate cancers detected on biopsies 1 and 2 were similar, but that cancers detected on biopsies 3 and 4 had lower grade, stage, and volume compared with biopsies 1 and 2; moreover, the third and fourth biopsies were associated with higher complication rates. When to stop the biopsy cascade that has started, especially for men with conditions known to elevate the PSA level, such as BPH and prostatitis, deserves more attention. This is important because many of these men will have false-positive screening results, which may have psychological and socio-behavioral consequences. While only 1 biopsied man in our study had more than 1 subsequent biopsy during the follow-up year, 25% of the biopsy group reported at the baseline survey having already had 3 or more sets of biopsies, suggesting that the strategy of repeated sets of biopsies is not uncommon.
Our study had a number of limitations. The absence of pre-screening data precluded the determination of whether men in the 2 groups had equivalent baseline psychological profiles. In addition, the 2 groups were not comparable at baseline with regard to history of benign prostatic hyperplasia, prostatitis, previous PSA tests, and previous visits to urologists. However, adjustment for these factors in logistic regression models predicting key outcomes from group membership did not change our findings. Also, men who had a previous prostate biopsy were excluded from the normal PSA group, but not from the biopsy group. However, when we restricted our analyses to include only those men in the biopsy group without a previous biopsy, the findings were essentially unchanged, except that with the reduced power from the restricted sample the difference between the groups responses to the question “In the past month, how much have you thought about prostate cancer?” lost significance at 12 months (P
= 0.16). Another potential limitation involves missing data; however, as the amount of missing data was small and the magnitude of the differences between groups was large it is unlikely that missing data made a difference in the findings from our study. Also, we obtained information about worry on the part of the spouse or significant other from the patient, rather than directly from the spouse or significant other22,23
; however, we believe the perception of the patient regarding worry on the part of their intimate partner is an important issue. We limited our study population to men with a primary care physician at 1 of the 3 participating institutions, anticipating that most of the men would be receiving their health care in that setting. However, men were not asked whether they had any PSA tests or prostate biopsies performed elsewhere, and, therefore, it is conceivable that the number of follow-up PSA tests and prostate biopsies that we obtained from our electronic medical record review at the 3 participating institutions is an underestimation. Lastly, the sample primarily included well-educated white men, and the results may not be generalizable to other racial and ethnic groups, and men with less education. We recommend verification of the results of this study in other samples, particularly African Americans, who are at higher risk for prostate cancer.
In conclusion, we found that even benign prostate biopsy results have psychological, socio-behavioral, and medical consequences. For many men, the benign biopsy result does not put the question of prostate cancer to rest; but rather, is associated with additional urology visits, PSA testing, and prostate biopsies, all of which have consequences for the patient and his family. We do not know the relative contribution of patient and urologist concern to the patterns observed, but it is certainly clear that men with benign biopsies receive more follow-up medical care than those with normal PSA results. These hidden tolls associated with screening should be considered in the discussion about the benefits and risks of prostate cancer screening, particularly in men with benign prostatic hyperplasia or prostatitis, who are at higher risk of false-positive screening results. Although it may be the path of greater resistance,24
physicians will better serve patients by acknowledging that screening for prostate cancer, although an attractive option for many, is not the best option for all.25