Expectant management of men with biochemical recurrence after first-line therapy for early stage disease

In theory, expectant management (e.g., watchful waiting or active surveillance) is a clinical option after the failure of any type of first-line treatment for localized prostate cancer, including:

  • Radical prostatectomy
  • External beam radiation therapy
  • Brachytherapy
  • Cryotherapy
  • High-intensity focused ultrasound (HIFU)

One might very reasonably ask why on Earth any man who had failed first-line therapy for localized prostate cancer might be willing (let alone eager) to consider expectant management as an appropriate form of care when his PSA was rising. Indeed , the younger that man is, and the faster his PSA is rising, the crazier that notion would seem to be.

However, since there appear to be no data to support or refute the validity of this option following biochemical recurrence after any form of first-line care, let us consider a case example …

Harvey K. is 71 years old and a former advertising executive. He is well off, recently retired after selling his ad agency, fit and healthy for his age, and recently re-married. When he was 69 years of age, and a widower, he had a rising PSA of 3.1 ng/ml and was diagnosed with clinical stage T1c prostate cancer, two positive cores, and Gleason 3 + 4 = 7. After much agonizing, Harvey and his then fiancée of 3 months agreed that he would have a radical, nerve-sparing prostatectomy, to be carried out by one of the very best known prostate cancer surgeons in the country. They were very much in love, knew the risks they were taking, but (to quote Harvey), “Damn it, I’d rather try and fail than spend the next 4 years worrying about it and then decide to do something when the risk of a poor outcome was increasing.”

Harvey and his fiancée were lucky. The pathology report showed pT2a disease, with no sign of cancer outside the prostate, no positive surgical margins, and only two foci of cancer, still Gleason 3 + 4 = 7. Three weeks post-surgery, Harvey was fully continent (apart from the occasional leak when he overdid the weight-lifting). Five months after surgery, Mr. and Mrs K. were married; Harvey’s PSA was < 0.03 ng/ml; and reports of the joys of the honeymoon were stellar! These things do happen.

Nearly 2 years later (21 months to be precise), Harvey’s PSA is 0.25 ng/ml. His urologist re-draws blood immediately (making every attempt to ensure that there is no risk of abberant PSA measurements being taken). The second result comes back at 0.24 ng/ml. Three months later, Harvey’s PSA is 0.28 ng/ml. Harvey is in biochemical failure. Now what?

Mrs K. is ready to throw the book at the problem and wants Harvey to have radiation, hormone therapy, and anything else that the medical profession can think of. She wants Harvey alive at all costs. Harvey has a whole different perspective!

“I’ve been married to you for just 18 months and 23 days,” he says to Mrs. K., holding both her hands in front of his urologist. “We’re still making love three nights a week and we both love it! You want to give that up? ‘Cos I’m not ready to do that yet!”

He turns to the urologist: “What’s my PSA doubling time?”

“I know you’ve done all your homework, Harvey,” starts the urologist, “So I’m not going to try to talk you into something you are dead set against but you need to …”

“What’s my PSA doubling time?” Harvey asks again gently.

“Probably somewhere between 12 and 18 months,” replies the urologist.

Now we all need to understand that a PSADT  of 12-18 months shortly after a diagnosis of biochemical failure is no guarantee that it will stay that low. But Harvey is clearly not ready to risk the joys of recent marital bliss. A compromise is reached. Harvey will have his PSA re-measured every 3 months, on the dot. If the PSADT clearly falls below 12 months, Mr. and Mrs K. will have a second and serious discussion with the doctor (and Harvey knows that means “or else”).

Is Harvey a typical patient? Maybe or maybe not. He certainly sounds like some typical patients, but he is a fiction.

The question that needs to be considered is very simple, however. Can you appreciate why Harvey was so sure he wanted to make this decision in favor of expectant management. I’m quite sure I do!

Are there good clinical reasons to justify Harvey’s decision (quite apart from the personal ones)? Well, yes, in fact there are:

  • First, median survival for men with a slowly rising PSA following biochemical recurrence is by no means short, even if they have no therapy until they need hormone therapy for metastatic disease. There certainly are men who die quickly of prostate cancer. But there are also many men who will survive for well over a decade.
  • Second, there are no data from randomized, double-blind trials indicating that any form of salvage therapy extends prostate cancer-specific or overall survival in men who have a biochemical recurrence after surgery.
  • Third, the data published by Stephenson from a multi-institutional cohort of 1,540 men treated with salvage radiotherapy after surgical failure suggest that slightly less than half of these men will have  6-year progression-free survival, and then only if they are treated when their PSA level is < 0.50 ng/ml.

Using the Kattan nomogram for salvage radiotherapy post surgery, we can currently calculate Harvey’s prognoses as follows:

  • If he has radiotherapy now, and his PSA doubling time is 12 months, he has a 50 percent probability of 6-year biochemical recurrence-free survival.
  • If he had radiotherapy now, and his PSA doubling time is 18 months, he has a 54 percent probability of 6-year biochemical recurrence-free survival.
  • If he waits until his PSA reaches 0.5 and his PSA doubling time is still at least 12 months, he has a 44 percent probability of 6-year biochemical recurrence-free survival.
  • If he waits until his PSA reaches 0.5 and his PSA doubling time has dropped to (say) 9 months, he still has a 39 percent probability of 6-year biochemical recurrence-free survival.

Many patients who are faced with this sort of decision react, understandably, with fear of the unknown, and decide on early treatment. However, like many men in the advertising business, Harvey has been trained to take risks, and does so thoughtfully but willingly. In about 5 years (if we remember) we’ll let you know how Harvey is doing!

Content on this page last reviewed and updated December 30, 2008.
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