Testicular Atrophy and the Aggressiveness of Prostate Cancer

ABSTRACT & COMMENTARY

Synopsis: Assessment of testicular histology was undertaken in 78 patients who had therapeutic orchiectomy for advanced prostate cancer. Among 35 patients who had orchiectomy for progressive disease after primary radiation therapy to the prostate bed, 25 had prominent testicular atrophy and the stage and grade of their original prostate tumors were higher. Survival was worse when compared to the 10 who did not have prominent testicular atrophy. Similarly, of the 25 men who presented with advanced (Stage D2) disease and were treated by orchiectomy, the seven who were found to have prominent testicular atrophy had shorter survival when compared to the 18 without prominent atrophy. Thus, the presence of prominent testicular atrophy at the time of therapeutic orchiectomy identifies a subset of patients with more aggressive disease and worse prognosis.

Source: Danniell HW. Cancer 1998;83:1170-1173.

Orchiectomy is a commonly prescribed surgical intervention for men with prostate cancer who have recurrence after local excision or radiation or who present with metastatic disease. Whereas this usually results in gratifying (albeit temporary) tumor regression in the great majority of patients, there is significant variability, and, in some patients, there is no response. In a series of patients who underwent orchiectomy for prostate cancer, the degree of testicular atrophy was determined by histological analysis and correlated with prostate cancer grade and patient survival.

Thirty-five patients had orchiectomy after progression from primary radiation to the prostate bed. Of these, 25 had testicular atrophy, and those with atrophy had worse five-year, tumor-specific, post-orchiectomy survival when compared to the 10 men without testicular atrophy (30% vs 89%; P = 0.02). Furthermore, a review of the original tumor histology in these patients indicated that these 25 men had tumors of more advanced stage and with higher histological (Gleason) grade.

Included in the series were 25 patients who had not received prior radiation but presented with advanced (Stage D2) disease and had orchiectomy as primary therapy. Seven of these men had prominent testicular atrophy, and they, too, had more undifferentiated prostate cancer histopathology and shorter survival when compared to the 18 patients without testicular atrophy. For this group, tumor-specific, post-orchiectomy survival at two years was 43% for those with prominent atrophy compared to 72% for those without.

There were an additional 18 patients who underwent orchiectomy for non-Stage-D2 disease and had not received prior radiation therapy. Of these, five had prominent atrophy and 13 did not. For this subset, there was no difference in survival after orchiectomy, with a total of only three deaths during the study period.

Danniell concludes that the demonstration of testicular atrophy at the time of therapeutic orchiectomy for prostate cancer is associated with poor post-orchiectomy prognosis.

COMMENTARY

In these days of molecular/genetic probing for prognostic factors, it is easy to overlook the obvious. Indeed, if Danniell had found that the over-expression of a certain gene correlated as strongly with survival as did the presence of prominent testicular atrophy, the paper might have elicited a swell of excitement. It might be argued that under that circumstance, the genetic marker might lead to an increased understanding of the pathogenesis of the disease. Yet, the same could be said about this paper.

It has been known for some time that low serum testosterone levels portend a worse prognosis for patients in whom hormone ablation therapy is to be undertaken.1-3 It stands to reason that if the tumor has developed in an androgen-depleted state, it is less likely to be androgen-dependent and, therefore, is more likely to demonstrate autonomous hormone-independent growth and be more aggressive. Although not reported in this series, it is likely that testicular atrophy would be associated with low serum testosterone levels.

Testicular histology at the time of therapeutic orchiectomy might prove to be a useful (and inexpensive) clinical tool in assessing the likelihood of sustained response to hormonal ablation. With the advent of effective palliative chemotherapy for prostate cancer patients who have progressed after hormonal ablation,4 perhaps those with prominent testicular atrophy at the time of orchiectomy could be considered candidates for alternative, adjunctive approaches as well.

References

1. Haapianinen R, et al. Prostate 1988;12:325-332.

2. Eriksson A, et al. Prostate 1988;12:249-256.

3. Kries W, et al. J Clin Oncol 1990;8:870-874.

4. Oh WK, et al. J Urol 1998;160:1220-1229.