Title: Re: long-term outcome following three-dimensional conformal/intensity-modulated external- beam radiotherapy for clinical stage T3 prostate cancer
Authors: Van Poppel, Hendrik
Issue Date: Dec-2008
Series Title: European Urology vol:54 issue:6 pages:1440-1441
Abstract: Expert's summary:
The authors review their long-term tumor control outcome for 296 patients aged 45–84 yr with clinical T3 disease who were treated with conformal radiotherapy in prescribed doses ranging from 6600 to 8640 cGy. The regional lymph nodes were not treated. Sixty-four percent of the patients received 3-mo neoadjuvant androgen deprivation therapy. Salvage androgen deprivation therapy was administered if the prostate-specific antigen (PSA) doubled in <3 mo.

The 5- and 10-yr PSA relapse–free survival rates were, respectively, 69% and 44% for T3a tumors and 49% and 32% for T3b tumors. As expected, the combination of doses above 81 Gy and androgen deprivation therapy resulted in 10-yr local control rates of 88%. The 5- and 10-yr distant metastases–free survival rates were, respectively, 85% and 73% for T3a tumors and 49% and 32% for T3b tumors.

The authors conclude that these results appear to be at least comparable, if not superior, to the outcomes reported in selected patients who underwent radical prostatectomy for clinical stage T3 prostate cancer and that radiotherapy is the standard treatment option.
Expert's comments:
The views of radiation (and medical) oncologists are important when prostate cancer management is discussed, but often the treatment-oriented experts look at it from a narrow angle. Urologists know very well that there are options other than surgery to treat, cure, or palliate. They are one of the only organ-based specialists who see the healthy man, the man at risk, and the early prostate cancer patient as well as the advanced prostate cancer patient, the metastatic cancer patient, and the patient who finally dies from the disease. While often surgery will have a place somewhere in the course of this chronic illness, urologists will be able to select the patients who will benefit from other treatments.

The urologist will decide when patients can be equally good or better off with external-beam radiation therapy with or without hormones. He or she identifies those who could eventually benefit from brachytherapy and those who might be better off with a seed implant than with active surveillance. The urologist is the expert who will propose and discuss the different treatment modalities and their results and complications. He or she will prescribe and administer medical treatments and eventually present the patient to a medical oncologist to initiate intravenous cytotoxic chemotherapy.

In this paper, it is obvious that there is a bias in the interpretation of the literature results.

The fact that surgery monotherapy will probably not cure many patients with clinical T3 prostate cancer is not an argument to claim that they should not have surgery at all. The results in terms of cancer-specific survival in clinical T3 prostate cancer patients who are treated with surgery initially (and sometimes exclusively) and then eventually received early or late radiotherapy or hormonal treatment are indeed excellent and exceed those obtained by radiotherapy with or without short- or long-term androgen deprivation. T3 prostate cancer is a disease that often warrants multimodal treatment, and it could well be that three treatment modalities in certain settings achieve better results than just one or two [1].

Exactly like the technique of radical prostatectomy, the quality of radiotherapy has much improved during recent years, and expert radiation oncologists are able to deliver dosages up to 86 Gy with obviously better local tumor control without adding much toxicity when compared with more conventional lower doses. It is clear that local control matters, and older series with lower doses (70–78 Gy) did not achieve good local control, since it was shown that in the 2-yr postradiotherapy biopsy, cancer was still present in nearly one-third of the patients [2]. It is noteworthy, however, that the number of patients who underwent salvage androgen deprivation for treatment failure is higher than in recent surgical series. Treatment failure was defined as biochemical relapse (111/150), local progression (22/35), or distant relapse (84/94).

The authors argue that in the surgical series, patients were selected, which is obviously correct, and most reports concerned patients with clinical unilateral T3a disease. Nevertheless, we have recently shown that for clinical T3b patients [1], and in those with PSA >100 ng/ml [3], 10-yr cancer-specific survival was 83.9% and 80.5%, respectively, when radical surgery was the first step in a multimodality treatment approach. Moreover, in the selected clinical T3a cases treated with surgery, a substantial amount will never need any second treatment. When these patients are all treated with radiotherapy, they all need hormone treatment (probably best for 3 yr), with well-known negative side effects and increased cardiovascular morbidity, even if administered for a short term [4] and [5]. After radical prostatectomy, serum PSA measurements allow hormonal therapy to be postponed in a fair number of patients, while radiotherapy-treated patients all need it because of the proven benefit of the combination treatment.

Actually, the results presented by Zelefsky et al are as expected—better with higher dose, better in lower stages, and better with hormones—but the results should not be compared with old series of radical prostatectomy monotherapy (reference 7 in Zelefsky et al). The statement that complete resection is not possible in those patients with gross extracapsular extension and with T3b is incorrect. Equally, it has not been shown that a more advanced local stage increases the risk of morbidity of the surgical procedure (reference 24 in Zelefsky et al), and it has also not been shown that the addition of radiotherapy after radical prostatectomy induces significant morbidity in more than just a few patients.

In contrast, the authors have clearly pointed out the drawbacks of the study report. The average and median follow-up is too short for prostate cancer, even locally advanced, since 15-yr cancer-specific survival rates are needed to evaluate treatment efficacy. The need for a randomized clinical trial that compares surgery and radiotherapy must be stressed, although it is unlikely ever to happen. This paper is, however, a valuable contribution that merits its place in the best-cited urological journal to date. Interaction between urologists and radiation and medical oncologists dedicated to urology will be fruitful as far as all parties are really interested in the urological cancer patient and do not at the same time claim that they are able to treat with due expertise any other malignancy that can confront a human being. The interaction will benefit the patient who suffers prostate cancer and who now is often the pawn in a game where different experts fight each other to advocate and offer the patient the treatment that they deliver.
Publication status: published
KU Leuven publication type: DI
Appears in Collections:Urology Section (-)

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