BERKELEY, CA (UroToday.com) - Patient care was the main impetus for us to write our paper because we encounter, in our practices, a number of patients with ultra-high prostate-specific antigen (PSA). There is, however, limited information in the literature; in fact, the table in the manuscript reflects all we could find in our PubMed search regarding this scenario.
In the literature, ultra-high PSA is generally defined as PSA of > 50 ng/mL. In our work, we compared the treatment outcomes in patients with PSA ≥ 20 ng/mL, 50-99.9 ng/mL, and ≥ 100 ng/mL and found that with radical treatment, their outcomes are much better than generally believed. Furthermore, while our report describes a cohort of patients diagnosed from January 1990 – December 2001, the results in contemporary patients are likely to be even better because of the widespread adoption of technological advances such as image guidance, dose escalation, intensity modulated radiotherapy, increased use of androgen deprivation in association with radiotherapy, and for longer durations than with this cohort of patients.
There are many controversies in management of prostate cancer, e.g. PSA screening, active surveillance versus immediate radical treatment, etc. It seems contradictory to consider only conservative endocrine treatment in a patient in whom an aggressive cancer is found with ultra-high PSA. My co-authors and I challenge the commonly-held belief that a PSA level of > 50 ng/mL or even > 100 ng/mL indicates such a high likelihood of metastatic disease that only androgen deprivation therapy (ADT) is justified.
This is the largest series in the world on non-metastatic patients with ultra-high PSA at diagnosis. To our knowledge, the Saskatchewan prostate cancer database is the second largest in Canada, after British Columbia. We do not yet have a formal prostate cancer screening program, although an increasing amount of ad hoc screening has taken place since the test was first introduced to Saskatchewan in 1990.[1,2] Life expectancy in Saskatchewan is the longest among all Canadian provinces. It therefore makes sense, given the good health of many of our patients, to give patients radical treatment despite a high PSA.
We have received compliments from colleagues for this common sense approach, which corroborates randomized studies, although these studies do not limit patient eligibility to include only those with PSA > 50 ng/mL. The Scandinavian Prostate Cancer Group Study-7 and the Swedish Association for Urological Oncology-3 (SPCG-7/SFUO-3), compared endocrine treatment, with or without radical radiotherapy, and included patients with PSA of 70 ng/mL or less. It concluded that in patients with locally advanced or high-risk localized prostate cancer, the addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality and substantially decreased overall mortality.[3] Similarly, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) PR.3/Medical Research Council (MRC) UK PR07 trial, comparing lifelong ADT without or with the addition of local radiotherapy, included patients with clinical T2 tumors with PSA concentration of more than 40 ng/mL.[4] It showed that the addition of radiotherapy to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70 respectively; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033).
With all these data, it is expected to change clinical practice worldwide and challenge the currently-accepted standard that ADT alone should be the treatment of choice for prostate cancer with very high PSA. There should be no hard cutoff regarding PSA eligibility for radical treatments, radical prostatectomy, or radiotherapy. Our study, combined with the literature, leads us to conclude that ultra-high PSA in and of itself should not disqualify patients from being offered radical treatment if it is otherwise a reasonable option based on patient and tumor factors.
References:
- Skarsgard D, Tonita J. Prostate cancer in Saskatchewan Canada, before and during the PSA era. Cancer Causes Control 2000;11(1):79-88.
- Tonita JM, Skarsgard D, Muhajarine N. Changes in case mix and treatment patterns in prostate cancer in Saskatchewan during the prostate specific antigen testing era. Cancer Causes Control 2009;20(2):201-9.
- Widmark A, Klepp O, Solberg A, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 2009;373:301-8.
- Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet 2011;378:2104-11.
Written by:
Patricia Tai, MB; Jon Tonita, PhD; Carla Woitas, CHIM; Tong Zhu, MSc; Kurian Joseph, MD; and David Skarsgard, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Saskatchewan Cancer Agency, Regina, SK Canada
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