The myth that younger men should not pursue active surveillance

In spite of no evidence to back up their assertion, I continue to hear urologists say things like "If you were older, I'd recommend active surveillance. But because you're young, you should have surgery for your low risk prostate cancer now while your recovery will be better." We saw, in a previous article, that immediate surgery rather than active surveillance only resulted in more years of expected misery from impotence and incontinence: see: "Can a man be too young for active surveillance?"

Now, a new study from Memorial Sloan Kettering Cancer Center examines the evidence for potency preservation. The authors, who include John Mulhall, the sexual medicine specialist, demonstrate that the expected loss of erectile function is never compensated for by better recovery in younger men and the age-related decline in erectile function over the years while waiting on active surveillance.

They used a standard questionnaire, the International Index of Erectile Function 6 (IIEF6). It is sometimes called the Sexual Health Inventory for men (SHIM). There are six questions, and the best score (excellent erectile function) is 30. The questions are:

1. Over the last month, how often were you able to get an erection during sexual activity?
2. Over the last month, when you had erections with sexual stimulation, how often were your erections hard enough for penetration?
3. Over the last month, when you attempted intercourse, how often were you able to penetrate your partner?
4. Over the last month, during sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner?
5. Over the last month, during sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
15. Over the last month, how do you rate your confidence that you can get and keep your erection?

All men filled out the questionnaire before surgery and periodically for two years. They excluded high risk patients who wouldn't be eligible for active surveillance, and any men who did not have bilateral nerve-sparing surgery. Men who had hormone therapy or salvage radiation were also excluded. There were 1,103 men in their cohort of men treated with RP at MSKCC between 2009-2013. Needless to say, MSKCC has some of the best, most experienced surgeons in the world.

They first looked at the baseline scores by age to get an understanding of how erectile function declines with age. This defines the expected erectile function if there were no surgery. They also looked at actual scores after surgery for each age. The difference between actual and expected shows the true effect of surgery on erectile function, with compensation for age-related decline and for the time delay caused by active surveillance.

They found that:

• Each year increase in age reduced the IIEF6 score by -0.27
• Erectile function recovery after RP declined by -0.16 for each year older at the age of treatment

While younger men started with a higher erectile function score, and their recovery after RP was better, it was never good enough to be better than the erectile function of an older man who didn't have surgery. At all time points, they would have been better off if they had delayed treatment and stayed on active surveillance. There was no "window of opportunity" where younger age recovery exceeded what would be expected to happen if they waited.

The authors conclude:

Small differences in erectile function recovery in younger men are offset by a longer period of time living with decreased postoperative function. Better erectile recovery in younger men should not be a factor used to recommend immediate surgery in patients suitable for active surveillance, even if crossover to surgery is predicted within a short period of time.

I hope patients whose urologists spout the myth that "early surgery will lead to better long-term erectile function than delaying until he is older" will email this important study to them and ask for comment.

Ageism in Prostate Cancer Treatment

We’ve all heard the age-related treatment recommendations of doctors. Comments like:

• “I don’t recommend surgery for patients over 70.”
• “Active surveillance is only for older men.”
• “Radiation is only for older men.”
• “After a certain age, there’s no point in doing anything beyond hormone treatment.”
• “There’s no need to test PSA or perform digital rectal exams on men over 70.”

Some such statements have some evidence behind them, some are historical relics, and some are neither. In fact, there is a distinct lack of evidence about prostate cancer treatments in older men.

Radical treatment for low-risk disease remains controversial at any age. However, the question remains: can treatment of high risk or locally advanced prostate cancer provide a survival benefit in the elderly?

In an editorial in the Journal of Clinical Oncology titled “Ageism in the treatment of high-risk prostate cancer: how long will clinical practice patterns resist the weight of evidence?” Shumway and Hamstra made the following points:

• Two-thirds of high-risk patients over 75 years of age receive only primary androgen deprivation therapy (ADT) or no treatment at all, and that has been increasing over time.
• Older men are more likely to be diagnosed with high-risk disease, and account for half of all prostate cancer-specific deaths.
• The average life expectancy of a 75-year-old US man is 11 years, and the 10-year cause-specific survival of high-risk men conservatively treated (i.e., without radical treatment) is 74%, so many doctors are hesitant to treat. The patient is more likely to die with the cancer than of the cancer.

On the other end of the risk spectrum, older men with low-risk disease are often over-treated. Daskivich et al. found that men with low- or intermediate-risk disease and co-morbidities that lowered life expectancy to under 10 years were often aggressively treated, yet there was no survival benefit to such treatment. Indeed, the survival benefit to immediate radical treatment of low-risk men of any age has been called into question by the PIVOT study.

Kowdley et al. argued that it is not chronological age, but physiological age that should be assessed in making a cancer surgery treatment decision. They further argue that it is overall health status, rather than age that must be assessed in the screening decisions. This runs counter to the AUA recommendation on prostate cancer screening, which argues against screening men over 70 years of age.

Surgery vs. Expectant Management in Older Men

A Japanese study last year by Mitsuzuka et al. looked at 333 matched pairs of men treated with prostatectomy. In each pair, one was older than 70 years of age, one was younger. They were matched on pre-operative factors (i.e., PSA, positive cores, Gleason score, clinical stage, and risk group). They turned out to be very similar on post-operative pathology as well (i.e., stage, Gleason score, positive margins, and lymph node invasion). The older group had higher cancer volume, however.

After 5 years of follow up, the biochemical recurrence-free survival was not significantly different between the younger men and the older men, 83% and 80%, respectively. Five-year

prostate cancer-specific survival and overall survival were similar as well.

It should be noted that a similar matched pair analysis from Cleveland Clinic by found that biochemical recurrence-free survival was 85% lower in the older cohort. Neither study reported on adverse events associated with radical surgery in the elderly.

A randomized clinical trial of prostatectomy compared to watchful waiting, the PIVOT trial, did not find a statistically significant survival difference in the older cohort. After 12 years of follow up, 8% of men aged 65 years and over who were only watched died of prostate cancer compared to 6% who had surgery. The difference was not statistically significant. Among men under 65 who were only watched, 9% died of prostate cancer, compared to 5% among those surgically treated. The difference between younger and older men was again not statistically significant. The difference may be clinically significant for high-risk older men, but the PIVOT trial was underpowered for that subgroup, so no determination can be made.

Another randomized clinical trial of prostatectomy or watchful waiting in Scandinavia with 18 years of follow up, SPGC-4, found no survival benefit to surgery among prostate cancer patients 65 years of age or older; however, there was a significant reduction in the risk of metastases with surgery. A Swedish study, Nilsson et al., found that age at the time of surgery predicted long-term urinary incontinence with a relative increase of 6% per year. Age at time of surgery also affects expected erectile function, according to Alemozaffar et al.

Liu et al. at Johns Hopkins used a Monte Carlo technique to simulate outcomes from active surveillance vs. surgery by age. They found that active surveillance had a net benefit in terms of quality-of-life years for low-risk prostate cancer patients older than 74 in excellent health, older than 67 in average health, and older than 54 in poor health. Yet, in 2009, twice as many men over 70 years of age had a radical prostatectomy compared to expectant management(26% and 13%, respectively) according to figures quoted by Maurice et al.

In the absence of data from larger randomized clinical trials, and the known risks of surgery in the elderly, such decisions much be approached carefully, especially among those with significant co-morbidities. NCCN recommends against surgery in low- or intermediate-risk men with life expectancy under 10 years.

Palliative Radiation/Conservative Treatment in the Elderly

The use of palliative radiation in elderly cancer patients has been decreasing over the years. In addition, its use decreases steadily by age, raising questions about under-treatment of the elderly. The following data were found by Wong et al. in the SEER/Medicare database:

Many kinds of conservative treatment for prostate cancer, i.e., treatment without curative intent, also seem to be under-utilized among the elderly. Conservative treatments may include ADT, chemotherapy, spinal surgery, and palliative radiation to metastases.

Echoing the findings of Wong et al. in all cancer patients, Lu-Yao et al. analyzed the SEER/Medicare database and found that only 7% of high-grade prostate cancer patients over 75 years of age received palliative treatment beyond ADT, compared to 21% of high-grade patients between 66 and 74 years of age.

Radiation Plus Hormone Therapy in High Risk/Locally Advanced Older Men

Bekelman et al. published the results of a set of analytic studies designed to determine whether the combination of androgen deprivation therapy (ADT) and radiation therapy (RT) confers a survival benefit in older men with high risk or locally advanced prostate cancer over treatment with ADT alone. While two randomized clinical trials (RCTs) – NCIC CTG and SPGC-7 – have proven a survival benefit to the combined treatment in the age groups they studied, older men were under-represented in those studies. In spite of that convincing evidence, 40% of high-risk, elderly men are treated with ADT alone. Lacking evidence from RCTs, Bekelman et al. mined the SEER/Medicare databases to see if any convincing evidence could be gleaned from them. They looked at three cohorts:

•  The “RCT cohort” was matched as closely as possible to the two available RCTs on this subject. These men were:

o   65 to 75 years of age, and

o   Stage T2 (organ confined) and Gleason score 5 to 7 or Gleason score 8 to 10, or

o   Stage T3 and any grade

o   4,642 were treated with ADT alone; 8,282 with ADT + RT

• The “Elderly cohort” was defined as:

o   76 to 85 years of age, and

o   Stage T2 (organ confined) and Gleason score 5 to 7 or Gleason score 8 to 10, or

o   Stage T3 and any grade

o   8,694 were treated with ADT alone; 5,546 with ADT + RT

• The “Screen-detected cohort” was defined as:

o   65 to 85 years of age, and

o   Screen-detected, stage T1c and Gleason score 8 to 10

o   2,017 were treated with ADT alone; 2,260 with ADT + RT

·      Other variables collected were: co-morbidities, race, ethnicity, marital status, census tract median income, and the size of their urban area.

(Note: The RCT and Elderly cohorts include some men who were not high risk because of database limitations.)

Their findings are summarized below:

Compared to the younger men in the two RCTs, older men had about the same or greater reduction in prostate cancer-specific mortality and in all-cause mortality when they were treated with RT in addition to ADT.

Dr. Bekelman added the following comment:

“I generally think that doctors and patients should discuss the individual treatment decisions that older men face, including the evidence showing the benefits and risks of treatment.  For older men with prostate cancer, radiation therapy is well tolerated. There are risk factors that might increase risks of urinary or bowel toxicity, like prior history of transurethral resection of the prostate or inflammatory bowel disease, but these co-morbidities are independent of age. Age alone should not preclude patients and their physicians from considering curative cancer treatment.”

Conclusions

Taking these studies together, some generalizations can be made:

• Older men are generally under-represented in clinical trials for prostate cancer treatments.
• Older men who are low risk are generally over-treated, while those whose prostate cancer is high risk, locally advanced, or metastatic are generally under-treated.

As the baby-boom generation in the US ages, it will become particularly important to address these concerns. It behooves patients, their families, and their doctors to consider each case individually, and not make decisions based on chronological age alone.

Note: Thanks to Dr. Bekelman for allowing me to see the full text of his study, and for supplying important summary comments.

Can a man be too young for active surveillance?

There is a “conventional wisdom” that active surveillance (AS) is only for older men, and that younger men are better off having immediate radical treatment, typically prostatectomy (RP). By “better off” we mean that there is a better chance at cancer control, or that the side effects of treatment, particularly incontinence and impotence, will be milder if treated earlier. Let’s turn a spotlight on that conventional wisdom, and see if it holds up under scrutiny.

The screening protocol for men under 50 years of age that is advocated by Memorial Sloan Kettering (see this link and this one), and recently discussed here, has important implications for active surveillance. Autopsy studies have demonstrated prostate cancer incidence of 20-30% in men under 50, mostly low grade and indolent. With increased screening of this young cohort, there will be an increase in the current incidence rate (now at about 10%). These men will increasingly be urged by their urologists to seek radical treatment, primarily surgery. If their screening protocol is widely adopted, there is great danger of over-treatment for this age group.

Oncological Control

With up to 20 years of follow-up, the Klotz Active Surveillance Trial has demonstrated the safety of that protocol. Klotz reported that of the 993 patients, there were only 15 deaths (1.5%) due to prostate cancer. When he pooled together several active surveillance studies, he found that the combined disease-specific survival rate was 99.7%. A Gleason score of 8-10 on confirmatory biopsy and a PSA doubling time of less than 3 years were associated with mortality, indicating the importance of close monitoring and follow-up biopsies on any active surveillance protocol.

It is worth noting how long men entering the Klotz study were able to stay on active surveillance before their progression characteristics indicated that radical treatment was required. Most of the progression was found in the first 5 years after entering the program, and reached a plateau by 15 years.

Time on AS	Percent for whom no treatment was recommended
5 years	75.7%
10 years	63.5%
15 years	55.0%
20 years	55.0%

Age was not a risk factor for prostate cancer mortality. Klotz said, “Younger patients were not at increased risk of prostate cancer mortality.” In fact, in younger men, the risk of non-prostate cancer mortality was almost six times higher than the rate of prostate cancer mortality.

It’s important to understand how slowly low-risk prostate cancer typically progresses in young men, even without active surveillance; that is, even without an intention to treat if the cancer progresses. Based on the Memorial Sloan Kettering Nomogram, we can see that for a 45 year-old man in excellent health diagnosed with a Gleason score of 3+3, PSA of 4 ng/ml, and nothing felt on a digital rectal exam, he has a zero chance of dying of prostate cancer in the next ten years, and a 4% chance of dying of something else. Even if he lets it go for 15 years, he only has a 3% chance of dying of prostate cancer, and an 8% chance of dying of something else.

It has been observed that there are rare and virulent forms of prostate cancer that are more prevalent in men under 50, and particularly among younger African-American men (see this link and this link). This is irrelevant to the discussion of active  surveillance  because those men will seldom be good  candidates for active surveillance from the outset. And if they do get in, clinical progression will be noticed in any active surveillance protocol at a very early time. Still, it is a reasonable precaution to screen men under 50 for genetic markers when there is a family history of early prostate cancer; for example, Oncotype Dx, Prolaris, TMPRSS2-ERG fusion, PTEN loss, or BRCA2 mutations.

Advancing age at the time of diagnosis is associated with a worse prognosis. In an analysis of 205,551 cases in the SEER database (see this link), 15-year prostate cancer mortality rates increased steadily with age at diagnosis.

Age Group	15-year PC mortality
≤50	2.3%
51-60	3.4%
61-70	4.6%
≥71	6.3%

Once again, this observation is irrelevant to a discussion of active surveillance. Age was not found to be a prognostic factor after accounting for Gleason score, tumor stage and PSA. The higher risk older men would probably not meet the entry criteria for active surveillance (although, depending on co-morbidities, they may be good candidates for watchful waiting). Those older men with more virulent disease that do get into an AS program would most likely be soon found to progress and be safely treated in time.

Based on oncological prognosis, younger age should not be used to decide between active surveillance and radical therapy.

Continence

An argument for treatment for younger men has been that there is a higher chance of continence preservation after surgery among younger men who already have better continence. Let’s see what the real-world numbers look like.

Continence naturally declines with age. Population-based continence statistics on younger men is scarce, but we can reasonably assume that moderate to severe incontinence is a rare occurrence in a 45 year-old man, and for our purposes, let us suppose that a 45 year old, just diagnosed with low-risk prostate cancer, is fully continent. What decision maximizes his lifetime expected continence?

Age	A. No natural moderate or severe incontinence	B. Expected lasting continence for men treated at that age	C. Percent losing continence due to RP at that age	D. Probability of staying on AS if started at 45	E. Expected loss of continence due to decision to initially have RP rather than AS	F. Life expectancy (years)
45	100%	80%	20%	100%	20%	34
50	92%*	79%	13%	76%	10%	30
55	84%	74%	10%	64%	6%	25
60	81%	70%*	11%	55%	6%	21
65	79%	66%	13%	55%	7%	18
70	74%	63%	11%	55%*	6%	14
75	74%*	59%	15%	55%*	8%	11

Sources:

A.     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1060034/?page=4

B.     Younger cohort is from Johns Hopkins prostatectomy patients, older cohort is from University of Chicago: http://www.jurology.com/article/S0022-5347(06)01930-6/abstract http://www.jurology.com/article/S0022-5347(10)00017-0/abstract

C.     Column A – Column B

D.    Klotz, assuming plateau continues

E.     Column C x Column D

F.     Social Security actuarial tables

* extrapolated figures

Our fully continent 45 year-old man has about an 80% chance of retaining his continence if he has an immediate RP.  So, about 20% of 45 year-old men will lose continence if they decide for RP rather than AS. Those 20% will live with that loss of continence for 34 years.

If he chooses AS instead of RP, what happens in the next 5 years? He has some small natural deterioration of continence, roughly an 8% expected loss. If he has an RP 5 years from now, his expected continence is about the same at 79%. Therefore, his net expected loss of continence will be 13% if he remains on AS for the full 5 years. But he has only a 76% chance of staying on AS for the first 5 years. Therefore, his expected loss of continence due to the decision to go on AS at 45 and get treated at 50 is 10% - only half as much as if he had the RP at 45. And he will expect to live with that incontinence for fewer years.

If he chooses AS at 45 and manages to stay on it for the next 25 years without treatment (a 55% probability), his expected loss of continence (incorporating the probability of being able to go that long without treatment) is minimized, at only 6%. And he will only have to suffer the loss for 14 years.

With respect to preserving continence, the 45 year old man is better off going on AS and staying on it as long as he can. What’s more, it can be easily shown with a similar continence analysis that a man diagnosed with low risk prostate cancer at any age, is better off choosing AS over immediate treatment.

We have ignored the stress incontinence that persists even after “full” continence is restored. 34 years is a long time to worry about leakage every time a man coughs, sneezes, laughs or plays sports.

Potency Preservation

Potency is better preserved by prostatectomy while the patient is younger and fully potent. Is our 45-year old man, newly diagnosed with low risk prostate cancer and fully potent, better off having a prostatectomy immediately, or choosing AS? Let’s run the numbers.

Age	A. Expected potency without prostatectomy	B. Expected lasting potency for men treated at that age	C. Percent losing potency due to RP at that age	D. Probability of staying on AS if started at 45	E. Loss of potency due to decision to initially have RP rather than start with AS	F. Life expectancy (years)
45	100%	55%	45%	100%	45%	34
50	94%*	49%*	45%	76%	34%	30
55	87%	43%	44%	64%	28%	25
60	82%	35%*	47%	55%	26%	21
65	74%	27%	47%	55%	26%	18
70	60%	18%*	42%	55%*	23%	14
75	45%	8%	37%	55%*	20%	11

Sources:

A.     http://www.brachyjournal.com/article/S1538-4721(15)00003-3/pdf

B.     http://jama.jamanetwork.com/article.aspx?articleid=1104401 Supplemental content: eTable3 (97% had nerve-sparing surgery)

C.     Column A – Column B

D.    Klotz, assuming plateau continues

E.     Column C x Column D

F.     Social Security actuarial tables

* extrapolated figures

Our fully potent 45 year-old man has a 55% chance of retaining his potency if he has an immediate RP.  So, about 45% of 45 year-old men will lose potency if they decide for RP rather than AS. Those 45% will live with that impotence for 34 years.

If he chooses AS instead of RP, what happens in the next 5 years? He has some small natural deterioration of potency, roughly a 6% expected loss. If he has an RP 5 years from now, his expected potency will be a less too, at 49%. Therefore, his expected loss of potency nets out exactly the same (at 45%) if he remains on AS for the full 5 years. But he has only a 76% chance of staying on AS for the first 5 years. Therefore, his expected loss of potency due to the decision to go on AS at 45 and get treated at 50 is 34% - 11 percentage points less than if he had the RP at 45. And he will expect to live with that impotence for fewer years.

If he chooses AS at 45 and manages to stay on it for the next 25 years without treatment (a 55% probability), his expected loss of potency (incorporating the probability of being able to go that long without treatment) is only half of the expected loss due to immediate treatment, at only 23%. And he will only have to suffer the loss for 14 years.

With respect to preserving potency, the 45 year-old man is better off going on AS and staying on it as long as he can. What’s more, it can be easily shown with a similar potency analysis that a man diagnosed with low-risk prostate cancer at any age, is better off choosing AS over immediate treatment.

This analysis ignores other important sexual side effects that would certainly weigh against immediate prostatectomy. Those sexual side effects include loss of penile length and girth, climacturia, Peyronie’s, venous leak, dry orgasms, anorgasmia, and dysorgasmia. Baseline erectile function is seldom restored fully. Loss of libido and psychologically induced loss of erectile function and depression are common results of all the aforementioned. Even when erectile function can be induced chemically, there is significant cost attached to 34 years of ED medicines or injections.

Radiation

The choice is not nearly as clear when the decision is between AS and radiation therapy (either external beam or brachytherapy) for young low-risk patients. Incontinence is a very low probability side effect of radiation, and potency preservation is much better within every age group, chronic side effects of any kind are rare with modern technology. It is often argued that we don’t know how cancer control will change with 25+ years of follow-up after dose-escalated radiation. As we have seen (see this link), recurrence rates did not reach a plateau for RP or IMRT; however, if we were to examine low-risk patients only, it is likely that long-term results would be more stable for both surgery and radiation.

It is worth mentioning that there is another bit of “conventional wisdom” that does not hold up under scrutiny of the medical evidence. Many urologists incorrectly state or imply that the side effects of radiation are progressive and won’t show up for many years. Under that scenario, a 45 year-old man treated with radical radiation would eventually wind up with impotence 10 years later, as well as urinary and rectal problems. The PROSTQA study (see this link) of men treated in 1999 showed that most of the radiation-induced toxicity showed up early, and that much of the “late-term toxicity” observed may actually have been attributable to age, diabetes, and comorbidities (see this link).

The percent experiencing grade 2 or higher urinary toxicities (excluding incontinence) by 5 years, 8 years, and 10 years after treatment was:

• ·      IMRT: 8.6% at 5 years, 11.2% at 8 years, and 10 years (76% of 10-year total by 5 years)
• ·      BT: 4.3% at 5 years, 8 years, and 10 years (100% of 10-year total by 5 years)
• ·      RP: 3.1% at 5 years, 3.7% at 8 years, and 5.5% at 10 years (56% of 10-year total by 5 years)

Ironically, we would conclude  (erroneously) from the above that it is prostatectomy, rather than radiation, that has cumulative urinary side effects that progress most over time.

The percent experiencing grade 2 or higher rectal toxicities by 5 years, 8 years, and 10 years after treatment was:

• ·      IMRT: 7.8% at 5 years, 8 and 10 years (100% of 10-year total by 5 years)
• ·      BT: 1.7% at 5 years, 8 years, and 10 years (100% of 10-year total by 5 years)
• ·      RP: 0% at 5 years, 8 years, and 10 years (100% of 10-year total by 5 years)

We have seen in a previous commentary that erectile dysfunction due to radiation was lower than for RP within every age group, that it occurred within the first 9 months following treatment, and that half of the observed deterioration over time was due to the normal aging process.

The case for active surveillance and against radical treatment at a younger age is less convincing if radiation is the treatment of choice. It is for currently mostly a moot point because younger low-risk patients are seldom offered radiation therapy.

Conclusions

I have been personally influenced by the testimony of a 45 year-old man in my prostate cancer support group who was inconsolable and under treatment for suicidal ideation after the loss of continence and potency. Younger men who are single and suddenly find themselves to be impotent and incontinent often despair of finding a mate, and younger men who are married sometimes find their marriages on shaky ground.

It is also important to remember that the longer one is able to stay on AS, the higher the probability a cure will emerge from all the research now in the field. Already it seems that 5ARis (Proscar or Avodart) may delay or even reverse progression in low risk PC. There are a number of hormonal medicines and immunotherapies already being tested that might prove to be even more potent.

AS protocols are already improving, and will continue to be safer. Many institutional protocols now dictate that the first follow-up biopsy should be multiparametric MRI-targeted and/or targeted using a transperineal mapping biopsy. To avoid the danger of excessive biopsies in younger men, many institutions have moved off of the original protocol of annual biopsies. After the first follow-up biopsy, what happens next depends on what happened before. If there were no signs of any progression, the next biopsy can be two years later; after that, maybe 4 years with just an imaging study in between, etc. I know that even Johns Hopkins, which had the strictest AS protocol, relaxed their position on annual biopsies.

We have now seen that starting with AS is a more rational decision than starting with RP for all low risk men. However, the decision is often not a rational one, but is based on fear, traditional “baggage” carried over from other cancers, and the influence of loved ones, relatives and friends. In the end, the young patient must decide what he is most comfortable doing. Maybe it will be AS, maybe SBRT or brachytherapy, maybe surgery. What I am uncomfortable with is his doctor making those life-changing decisions for the patient, and ruling out any options without evidence. The low-risk patient certainly has plenty of time to investigate all options thoroughly for himself before coming to a decision. Taking one’s time often allows one to put emotions in perspective. Leaving all options open until one is ready to decide is the best stance to take. I have only seen treatment regret in men who didn't take the time to do that.