The Saturday prostate cancer post: November 1, 2008

There are a lot of news items this weekend. This first batch addresses studies on:

  • The incidence of clinically insignificant prostate cancer
  • Bladder and rectal cancers as side effects of radiotherapy for management of localized prostate cancer.
  • Fatigue in cancer patients in general (and prostate cancer therapy specifically).
  • The appropriate use of androgen deprivation therapy
  • Second line chemotherapy for castration-resistant prostate cancer.

Helpap and Egevad have further attempted to define the clinical risks associated with the non-treatment of men with “low-risk” localized prostate cancer. They regraded >1,000 consecutive core needle biopsy specimens of prostate carcinoma taken in 2007 according to the modified Gleason scoring system. The results were correlated to serum PSA level and tumor extent in the cores. They found that: patients with a PSA level <10 ng/ml and tumor extent <20 percent frequently (up to 55 percent) had Gleason scores of 6 or 7a; patients with a PSA level >10 ng/ml or tumor extent >20 percent had higher Gleason scores (> 7a); patients with tumor infiltration of < 1 mm in only one of up to 12 cores and PSA levels <10 ng/ml mainly had low Gleason scores (6 and 7a)>However, they also found that only 5 percent of the patients had biopsy results corresponding to such parameters. Furthermore, only 25 percent of such patients were confirmed to have a pT2a tumor after radical prostatectomy. They conclude that while “clinically insignificant” prostate cancer can be defined according to very restricted parameters (a Gleason score < 7a; tumor infiltration of ≤ 1 mm in only one core needle biopsy; and PSA of ≤10 ng/ml), and that active surveillance is feasible, with the agreement of the patient, such cases are actually relatively rare. [Note that according to the modified Gleason grading system, a Gleason score of 7a = 3 + 4 whereas a Gleason score of 7b = 4 + 3.]

A retrospective analysis of SEER data on nearly a quarter of a million men treated with radiotherapy or radical prostatectomy between 1988 and 2003 concludes that, “Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population. The risk of rectal cancer is increased in patients who receive external beam radiotherapy compared to radical prostatectomy. Patients should be counseled appropriately regarding these risks.” This analysis was carried out by staff of an academic department of urology. While these results may be accurate, one wonders if a similar study carried out by members of a department of radiation oncology might have reached a different conclusion that emphasized the occurrence of erectile dysfunction and incontinence! Caveat emptor.

Goedendorp et al. have addressed the issue of fatigue as it affects cancer patients generally (not just prostate cancer patients). It is well known that fatigue is a common complaint of cancer patients during and after treatment. What has never previously been studied is the occurrence of fatigue in cancer patients prior to their diagnosis. It this study, Goedendorp and colleagues have demonstrated that ~ 23 percent of cancer patients already experience severe fatigue before initiation of treatment. The actual range of occurrence of severe, pretreatment fatigue by type of cancer patient appears to be between 14.3 percent (for prostate cancer patients) and 28.1 percent (for gastrointestinal cancer patients).

Isbarn et al. have reviewed available data on the use of androgen deprivation therapy (ADT) in the management of prostate cancer. They note that ADT “is increasingly used for the treatment of prostate cancer …, even in clinical settings in which there is no evidence-based proof of prolonged overall survival.” The further note that, “Even short-term use of ADT may lead to numerous side effects, such as osteoporosis, obesity, sarcopenia, lipid alterations, insulin resistance, and increased risk for diabetes and cardiovascular morbidity.” They conclude that, “ADT is associated with an increased risk of multiple side effects that may reduce quality of life and/or [overall survival]. Consequently, these issues should be discussed in detail with patients and their families before initiation of ADT. ADT should be used with knowledge of its potential long-term side effects and with possible lifestyle interventions, especially in settings with the highest risk-benefit ratio, to alleviate comorbidities.”

Rosenberg and Oh have reviewed the current status of available options for chemotherapy for men with castration-resistant prostate cancer (CRPC) who fail first-line chemotherapy with docetaxel + prednisone (with or without estramustine phosphate). They conclude that, “Mitoxantrone therapy can be considered in select patients …;” that “Other cytotoxic agents such as carboplatin might have a limited role;” but that, “In general, patients with CRPC should be directed towards clinical trials, when available.”

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