Taking Time to Start XRT for Localized Prostate Cancer: It’s Not for Everyone

Abstract & Commentary

William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.

Synopsis: Delays in starting radiation therapy for high-risk localized prostate cancer were shown in this retrospective review to be associated with a greater risk for disease relapse, as witnessed by PSA recurrence. For patients with low-risk disease, however, comparable delays were not associated with greater risk for relapse.

Source: Nguyen PL, et al. Cancer. 2005;103:2053-2059.

A delay of 3 months between diagnosis of clinically localized prostate carcinoma and initiation of treatment is not uncommon for patients who ultimately choose radiation therapy. This interval is significantly longer than delays commonly observed for other cancers such as head and neck, cervical, lung or breast carcinoma. There are probably several reasons for this including the time for appropriate consultations, obtaining second opinions, etc, and possibly a complacency based upon a notion that prostate cancers are indolent and unlikely to progress rapidly.

Nguyen and colleagues performed a retrospective analysis to determine whether a delay in initiating external beam radiation therapy following diagnosis could impact prostate-specific antigen (PSA) outcome for patients with localized prostate cancer. For this, the data from 460 patients between 1992 and 2001 who received 3D conformal RT to a median dose of 70.4 Gy for T1c or T2 prostate cancers, without evidence of spread beyond the capsule were analyzed. The primary end point was PSA failure (American Society for Therapeutic Radiology and Oncology definition) and delay was measured as the time interval between diagnosis and initiation of treatment.1 Risk groups were defined by PSA at baseline, clinical T category, Gleason score and the percentage of biopsy cores positive for tumor.

Of the 460 patients, 220 were considered at low risk, and for them treatment delay was not a significant predictor of time to PSA failure (P = 0.31). However, in contrast, for those considered at high risk, treatment delay was a significant predictor of time to PSA failure (adjusted hazard ratio = 1.08; 95% CI, 1.01-1.16 per month; P = 0.029). The patients with high-risk disease had 5-year estimates of PSA failure-free survival of 55% if their treatment delay was greater than 2.5 months compared to 39% if the delay was less than 2.5 months (P = 0.014).

Comment by William B. Ershler, MD

Thus, for patients with high risk but localized prostate cancer, about half of treated patients of the current trial had a significant decline in disease-free survival. This, of course, would makes intrinsic sense to tumor biologists familiar with the relentless nature of cancer cells to grow and spread, particularly for those with biochemical or histological features of aggressive disease. Nonetheless, there is a commonly observed complacency in getting started with initial treatment for prostate cancer. Some of this is due to the availability of diverse treatments within radiation oncology (external beam, brachytherapy, etc), and, of course, surgery. It is not uncommon for patients to seek opinions from one or more surgeons as well as radiation oncologists, and then to deliberate for considerable time before making a treatment decision. Indeed, in this series, the median time from diagnosis to treatment was 2.5 months. It is unlikely that this is unique to the communities represented in this report. Patients who elect surgery are also likely to be treated after a delay. In this regard, 2 recent reports2,3 have shown that a delay of 3 months before prostatectomy was also associated with less favorable outcomes in patients with markers of high-risk (high baseline PSA or poorly differentiated) tumors.

Currently, neoadjuvant hormonal ablation is becoming more commonly used. For those with markers of high-risk disease and who anticipate a delay in definitive initial therapy, it might be reasonable to consider this approach. However, the use of such an approach in diminishing relapse rates in the context of initial treatment delays has not been established. Yet, if current trials of neoadjuvant hormonal therapy prove beneficial to radiation or surgery alone, it would seem a logical extension would be to so treat high-risk patients with localized disease while they are considering treatment options.

References

1. Mackillop WJ, et al. Int J Radiat Oncol Biol Phys. 1994;30:221-228.

2. Nam RK, et al. Can J Urol. 2003;10:1891-1898.

3. Moul JW, et al. J Urol. 2004;171:1141-1147.