[Influence of local treatment on the biology of advanced prostate cancer : Treatment of the primary tumor may delay hormone resistance of metastases]. / Einfluss von lokalen Therapiemaßnahmen auf die Biologie des fortschreitenden Prostatakarzinoms : Die Behandlung des Primärtumors kann die Hormonresistenz der Metastasen verzögern.

BACKGROUND: In metastatic prostate cancer, a trend towards longer survival has been observed over the last 15 years. Beyond progress due to new drugs, retrospective data also suggest a positive influence of a prior treatment of the primary tumor. OBJECTIVES: Can treatment of the primary tumor improve the prognosis of patients later developing metastases, and if yes, what are the underlying mechanisms. MATERIALS AND METHODS: In addition to a critical review and discussion of the literature, we analyzed the long-term outcomes of 115 patients with T4 prostate cancer, who had undergone radical prostatectomy after inductive hormonal therapy at our institution. RESULTS: Of the 115 patients, 84 developed prostate-specific antigen (PSA) recurrence during the further course of disease and must therefore be regarded as uncured. Tumor-specific and overall survival of these 84 patients after 150 months were 61 and 44%, respectively. A total of 47 patients were alive after a median follow-up time of 95 months, of whom 31 were still receiving standard hormonal therapy. Only 13 had developed resistance towards their primary hormonal therapy and, hence, received tertiary hormonal therapy. Again, long-term responses were found in some of these patients. CONCLUSIONS: Primary tumor resection, at least under the circumstances described here, seems to delay the development of castration resistance in metastatic prostate cancer or to completely prevent it in individual cases.

Extended longevity of reproductives appears to be common in Fukomys mole-rats (Rodentia, Bathyergidae).

African mole-rats (Bathyergidae, Rodentia) contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive "helpers" in their natal families, often for several years. This "reproductive subdivision" of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli), breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5-2.2fold depending on the sex), irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis) showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats.