Tuesday, August 30, 2016

Treatment delay in primary radiation therapy or surgery


Patients are often concerned about delaying treatment. Will it give the cancer a chance to metastasize? What if the random biopsy didn’t detect existing higher grade cancer? This is particularly of concern to patients considering active surveillance.

Dong et al. reported on the cancer control outcomes of 4,064 patients treated with external beam radiation therapy at Fox Chase Cancer Center. The patient records included:
  • 1549 low-risk patients, 1612 intermediate risk patients, and 903 high-risk patients
  • Median time-to-treatment was 3.3 months
After a median follow-up of 64 months:
  • There were no differences in 5-year biochemical failure, distant metastases, or overall survival depending on whether patients waited more or less than the median time to treatment.
  • This was true for every risk group.
  • This was even true for high-risk patients who did not receive any ADT.
This reflects the very slow natural history of prostate cancer progression, even with a high-risk diagnosis.

(Update) Lee et al. reported on the outcomes of 3,962 intermediate- and high-risk patients who all got a prostatectomy up to a year after their biopsy. After a median follow-up of 7 years:
  • Longer delays were associated with a decreased risk of castration-resistant, regardless of their risk group
  • Longer delays did not result in increased detection of metastases or deaths

The same holds true whether the final decision is surgery or radiation (or, of course, active surveillance). Koretz et al. tracked the oncological outcomes of men who delayed having surgery after a positive biopsy. They categorized the 1568 men into those who had an RP ≤60 days, 61-90 days, and >90 days after their biopsy. After 64 months of follow-up:
  • All three groups had about the same pathology outcomes: Gleason upgrade, extracapsular extension, seminal vesicle invasion, positive margins, and positive lymph nodes.
  • The 5-year biochemical recurrence-free survival was the same in all three groups.
  • Treatment delay had no effect even among high-risk men
Even longer delays had no effect on outcomes. Gupta et al. looked at very high-risk (GS 9/10), high-risk (GS 4+4) and unfavorable intermediate-risk (GS 4+3) men who had surgery within 6 months of their diagnosis. They compared outcomes between those who were treated in less than 3 months of diagnosis vs. 3-6 months. There was no difference in 5-year biochemical recurrence-free survival or metastasis-free survival. Patel et al. found that surgical delays of up to 6 months following prostate biopsy were not associated with an increased risk of Gleason upgrading, EPE, SVI, positive surgical margins, or lymph node involvement. Similarly, Reichard et al. reported no difference in biochemical failure, metastases, prostate cancer mortality, or all-cause mortality among high or very high risk men who delayed prostatectomy the longest. Lee et al. found that a treatment delay of a year before prostatectomy in intermediate and high-risk men had no effect on risk of developing metastases or all-cause mortality.

Hirasawa et al. found than men who delayed surgery for over 6 months had no worse outcomes than men who were treated sooner in Japan. Zanaty et al. found that delaying surgery only affected the high risk patients in Canada. Morini et al. found no loss of efficacy when surgery was delayed for more than 12 months in Brazil. Aas et al. found no decline in pathological findings, freedom from relapse, or prostate cancer survival after delaying prostatectomy for 6 months with 8 years of follow-up among intermediate or high risk men in Norway

Prostate cancer patients have enough time to meet with a variety of specialists and make a well-considered decision, irrespective of their risk level at the time of diagnosis.

Patients who are considering which kind of therapy is right for them should take comfort from this. They have sufficient time to meet with a variety of specialists and to gather the information they need to make a well-considered decision.

Patients who are considering active surveillance should also take comfort from this. Oncological outcomes were the same as for immediate therapy, whether men were treated with surgery or radiation. Those choosing surgery after active surveillance, may have worse continence and potency preservation, however (see this link). Delay in seeking therapy is not likely to adversely impact cancer control, even if they harbor a riskier form of the disease, at least in the short term. Of course, a confirmatory follow-up biopsy, especially one that is targeted using multiparametric MRI, will provide a much higher degree of assurance.

I have come to believe that no doctor ought to accept as final any prostate cancer primary treatment decision made by a low, intermediate, or high risk patient within a month of receiving his diagnosis, and preferably within 3 months. The emotional temperature has too strong an effect on decision making, and time is our friend in this regard. Similarly, doctors should insist that second opinions have been acquired.

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