By Mark Scholz, MD, PCRI + Prostate Oncology Specialists
AUA is an annual meeting of urologists where data from new studies are presented. This data is presented in abstracts, or summaries of the entire peer reviewed articles. In this article, Mark Scholz, MD, analyzes the data and explains the practical implications of these new studies.
Close to 600 new prostate-cancer-related studies were published at the annual American Urological Association meeting in San Diego this past May. In this article, I want to draw attention to three of the studies in particular. These three studies discuss the optimal timing for administering radiation after surgery, when the surgeon leaves cancer behind. Persistent cancer after surgery, if the PSA is undetectable, is called a positive margin. If the PSA is rising it is called a PSA relapse.
Obviously, there were many interesting reports presented at a meeting of this size. Around 15,000 urologists from all over the world attended. There were prostate cancer studies relating to PSA screening, hormone therapy, active surveillance, prostate imaging, radiation, focal therapy, and of course, surgery. There were far too many topics to cover in this short article. But before we delve into the three post-surgical radiation studies, I want to present results from two other new reports about surgery. I also want to present the results of another, about prostate cancer survival rates in general. First, the two reports about radical prostatectomy:
Abstract MP69-15: Mark Preston, MD, and other researchers looked into an association with the day of the week that surgery was performed and various outcomes such as operative complications, length of hospital stay, and mortality. This was a retrospective evaluation of the SEER database in 20,955 men. The study found that surgery performed on Monday was associated with an 11% reduced risk of short-term complications and a 17% reduction in the risk of long-term urinary complications. Surgery performed on Friday was associated with a 12% higher complication rate and 19% higher risk for a prolonged hospital stay (>2 days). Mortality was not affected by the day of the week. The authors pointed out that this phenomenon of inferior surgical results toward the end of the week has been reported with other types of surgery besides prostate surgery. They did not offer any speculations about the cause.
The next study addresses a serious side effect from surgery that I have rarely heard about. This preliminary report indicates that surgery has a major impact on the capacity to have normal orgasms.
Abstract MP80-03: Christopher Dechet, MD, and other researchers administered periodic questionnaires to 499 men after surgery. Sixty percent of the men reported that the ability to achieve an orgasm was worse; thirty precent reported no change and ten percent said it was improved. Recovery plateaued at 15 to 21 months. Age was not a material factor except in patients less than 50 years old. Nor did the use of robotic surgery affect the incidence of orgasmic dysfunction. Recovery of orgasmic function was closely associated with recovery of erectile function. The authors also noted that moderate to severe urinary incontinence was associated with worse orgasmic function. The authors concluded, “orgasmic function is negatively impacted by radical prostatectomy and takes 15 to 21 months to recover.”
The next study is interesting because it closely mirrors what I commonly see in my clinic. Patients tend to grossly overestimate their chances for dying of prostate cancer. The researchers imply that this misconception is due to information from the internet.
Abstract MP04-08: In this study the researchers evaluated how well US adults estimated survival for a hypothetical prostate cancer patient using an unrestricted internet search. After that was completed, survival was estimated with cancer-specific nomograms. All the participants were given a pathology report from a 69-year-old man who had surgery. The participants were asked to predict what the hypothetical patient’s 15-year survival would be using unrestricted internet searching. Afterwards, they were asked to re-estimate with a prostate cancer nomogram. 129 people participated in the study. Their average age was 47. Three-fourths had a college degree. After internet searching only 19% were able to offer a reasonably accurate assessment of the hypothetical patient’s survival. After using the nomogram, one-half of the participants came up with a reasonably accurate prediction of survival. The authors concluded that most adults seriously underestimate 15-year survival using unrestricted internet searching and that patients need help finding accurate online health resources.
Now let’s move on to the three abstracts that have important implications for men; cancer that has been left behind after surgery. Over 60,000 men in the United States are treated with radical prostatectomy every year. A positive surgical margin is detected immediately after surgery by the pathologist in 10-50% of men (the incidence is higher with unskilled surgeons and more serious cancers).
Men with positive surgical margins or a PSA relapse after surgery are often treated with radiation. Surgery is almost always associated with a slow recovery of urinary continence and sexual function, sometimes requiring up to 2 years. The problem is that there is also evidence that radiation further retards urinary and sexual recovery. Therefore, if radiation can safely be postponed or withheld altogether the chances are better for more complete urinary and sexual recovery. The results of the following study indicate that the impact of radiation on sexual function is the greater concern.
Abstract: MP04-11: In this study the authors administered questionnaires to 113 men at three specific time points: before surgery, after surgery but before radiation, and after radiation. The patients were divided up into two groups: The ones who had radiation within a year of surgery (median 8 months) and those who had more delayed radiation (median 28 months). The authors found that there was no significant difference in the rate of recovery of urinary function between the two groups. However, men receiving early radiation were found to have worse recovery of sexual function compared to the men whose radiation was administered later.
Since delaying radiation seems to be associated with better rates of sexual recovery, the next important question is what kind of impact does the timing of radiation have on cancer control. This is an important question because previously-performed trials show that radiation right after surgery in men with positive margins reduces the risk of future metastases and improves survival. The problem with these previously performed studies is that the men who had immediate radiation were only compared with men who had their radiation delayed until the PSA was 2.0 or higher. The next two studies address the important question, “Would there still be a survival advantage for immediate radiation over delayed radiation if men with positive margins were monitored very closely without any immediate radiation, but had radiation initiated at the very first sign of a PSA rise (above 0.5)?”
Abstract MP14-08: To answer this question, the authors of this study evaluated 596 men with positive margins after surgery, whose PSA was undetectable. The patients were divided into two groups: Those who had immediate radiation within 6 months of surgery while the PSA was still undetectable, and men who started radiation at the first indication of a PSA increase, before their PSA rose higher than 0.5. In the latter group 60% of the men never did develop a PSA increase and therefore never required radiation. However, in the other 40% delayed radiation was initiated after the PSA began to rise but before it increased above 0.5. Metastasis-free survival at 10 years for the first group, the men who had radiation right after surgery was 90%. For the other group, with either no radiation or delayed radiation, it was 89%.
Abstract MP14-12: In this study, the authors divided 422 men with positive margins into four groups: radiation right after surgery (PSA < 0.2), radiation started after a PSA relapse but while the PSA was less than 0.5 (the same as Abstract MP 14-08), radiation started after the PSA had risen above 0.5, and men who never received any radiation whatsoever, no matter how high the PSA increased. The men in the first two groups (immediate radiation and radiation with a PSA < 0.5) were 4.3 times less likely to develop metastases over the next 8 years compared to the other groups. There was no significant difference between the men treated with “early” (PSA <0.2) or “immediate” radiation after relapse (PSA < 0.5).
Both of these studies are retrospective. The problem with retrospective studies is that unsuspected factors can impact the accuracy of results. Despite this limitation, we now have two studies indicating that men with positive margins can safely forgo immediate radiation as long as they monitor their PSA levels very closely and initiate radiation at the very first sign of a PSA relapse.
While these two new studies address a very important question, men should realize that the presence or absence of positive margins is only one of many important prognostic factors that predict for cancer problems in the future. The other important factors are node status, the PSA level prior to surgery, the Decipher genetic test, and the Gleason score. The two studies I just presented should be applied to men who have a positive margin and otherwise have favorable prognostic factors. Such men can safely delay radiation until there is evidence of a PSA relapse. Conversely, men who have unfavorable prognostic factors need immediate aggressive multimodality therapy regardless of their margin status. The final study we will review addresses treatment for men with unfavorable prognostic factors.
Abstract MP50-01: Several luminary researchers, Drs. James Eastham, Peter Scardino, Francesco Montorsi, and Alberto Briganti, evaluated the use of aggressive post-op treatment in men with lymph node metastasis after surgery. Their study evaluated 1,338 men with node metastases who received immediate testosterone inactivating pharmaceuticals (TIP) and compared their survival rates with men who were treated with TIP plus radiation. The difference between the 10-year mortality risk of the men getting immediate combination therapy and those receiving TIP alone ranged from 5% in patients with low risk features to 40% in men with a high disease burden.
The results of all these new studies indicate that the selection of treatment after surgery should depend on the characteristics of each patient. Treatment, therefore, can range from observation, to radiation alone at the first sign of PSA relapse, to immediate combination therapy with hormone therapy plus radiation*.