Primary focal unilateral nerve sparing cryoablation for very early prostate cancer: is it enough or too much, or do we know?
T here are many controversies surrounding the management of low risk prostate cancer. It is clear that there are plenty of such patients who get overtreated, some are appropriately treated, some undertreated, and on occasion some not treated at all. Unfortunately, it is frequently difficult to tell exactly which of these things we are doing and which one we should be doing. This study by Truesdale et al is essentially attempting to bring clarity to this problem by defining a group of men who are appropriately treated with focal unilateral nerve sparing cryoablation (FUN cryo) for whom a favorable outcome might be expected. There is a reasonable rationale for believing FUN cryo might be an appealing option for localized prostate cancer involving 1 lobe. Two prospective studies support the efficacy of cryoablation as being comparable to or somewhat less effective than conventional external beam radiotherapy (EBRT) in men with locally advanced disease. The major downside to cryoablation seems to primarily be its association with a higher risk of erectile dysfunction (ED) This unilateral approach holds the promise of being less likely to cause ED and other treatmentrelated adverse effects than a full gland freeze, albeit with a yet to be defined risk of reduced effectiveness. Based on this report by Truesdale and colleagues, there seem to be some patients who fail FUN cryo because they have such high volume disease that a focal freeze is inadequate. How many fall into this category? Based on this study, it seems that patients with more than 2 biopsy cores may very well fall into this category, because 75% of them failed with 3 years using the Phoenix definition. However, 60% of patients with 2 biopsy cores or less failed by 7 years as well, so even they cannot really be defined as ideal for FUN cryo. One of the reasons it is difficult to identify the ideal patient for FUN cryo is that many of them may not need treatment at all. Evidence for this assertion comes from the fact that when the outcomes of less highly selected patients are compared after surveillance to definitive treatment, it is very difficult to show much difference. For example, the National Prostate Cancer Register of Sweden Follow up Study included 6849 patients 70 years or younger with local clinical stage T1 2 prostate cancer, a Gleason score of 7 or less, and a serum prostate specific antigen (PSA) level of less than 20 ng/mL. Survival outcomes after surveillance were compared with outcomes after curative treatment with either surgery or EBRT. Among the 6849 patients, 2686 had low risk prostate cancer (i.e. clinical stage T1, Gleason score 2Y6, and serum PSA level of G10 ng/mL) For those with low risk disease, the 10 year cancer specific mortality rate was 2.4% for the 1085 patients in the surveillance group and 0.7% among the 1601 patients in the curative intent group. Thus, even with more aggressive and presumably more effective treatment, the benefits at 10 years were modest at best, even in less wellselected patients. Therefore, it is likely that a very significant percentage of the men in the study of Dr Truesdale may not have benefited from any treatment. For the sake of argument (and example) if we assume that 50% of the patients who did well with FUN cryo were overtreated, then only 20% (one half of the remaining 40% with 2 or less cores) might have been appropriately treated. Unfortunately, we do not know how to prospectively define who this 20% is. Furthermore, this 20% is a rather tenuous number because the biochemical endpoint used has not been validated for men treated with cryosurgery. The endpoint used was developed for detecting clinically significant failure after radiotherapy but not cure. Thus, based on this assumption, it is likely that the cure rate with FUN cryo is somewhat less than 20% Based on the Swedish data described above and a Bback of theenvelope calculation[ (lower risk of mortality but less effective treatment) the improvement in cause specific survival at 10 years might be expected to be less than 2% for patients treated with FUN cryo compared with surveillance, with a substantially higher risk of complications. If an Bideal patient[ was identified, and such a patient was told he had less than a 20% chance of cure, associated with a less than 2% improvement survival from prostate cancer with an invasive surgical procedure requiring general or spinal anesthesia, at a not insignificant price, it would seem doubtful to me that very many men would select FUN cryo. Based on my comments above, one might get the impression that I have no enthusiasm for FUN cryo in the management for prostate cancer. Not quite true, there is a subgroup of patients for whom FUN cryo might be an ideal option. Highly selected patients failing definitive EBRT might fit into this category. For example, a relatively young and potent patient with an excellent performance status has a focal local recurrence. Such a patient ideally originally had negative biopsy results everywhere except the site of the index lesion (e.g. right lobe) and then received high dose (78 Gy+ EBRT to the entire gland. He now presents years later with a slowly rising PSA, a biopsy proven recurrence, and an endorectal magnetic resonance imaging scan suggesting that his disease is limited to the same site. For such a patient, lifelong androgen deprivation therapy or a salvage prostatectomy might be associated with excessive morbidity, but FUN cryo might just Bdo the trick[ It seems that, after EBRT, patients tend to fail at their original site of disease. These patients are not uncommon, and they may have a relatively unfavorable long term prognosis if not effectively treated. Focal unilateral nerve sparing cryoablation can effectively ablate unilateral disease and might put him at a lower risk of ED or urinary/rectal incontinence. INVITED COMMENTARY
Cancer journal