Ailments & Conditions:

Prostate Cancer

The following blog post is an academic article I wrote for my Masters of Health Science (Traditional Chinese Medicine) degree. It explains the TCM approach to treating prostate cancer.

Traditional Chinese Medicine playing an active supportive care role for prostate cancer

By Nick Conquest

Introduction

Prostate Cancer (PC) represents a high proportion of all male cancers. In Australia the rate of PC appears to be rising steadily (Feletto et al., 2015). Surgery, hormonal therapy or radiation are common treatment strategies. Each treatment option can have a number of complications or side effects, which in turn have an affect on life quality(Michaelson et al., 2008). Traditional Chinese medicine (TCM) represents a complementary alternative medicine (CAM) frequently utilised by PC patients (Klafke, Eliott, Wittert, & Olver, 2011).   The modalities of acupuncture and Chinese herbal medicine are known to treat complications of PC treatment such as erectile dysfunction and hot flushes. However, the current evidence substantiating the efficiency of these modalities is lacking. For low risk PC, a common treatment approach is active surveillance or watchful waiting. It is possible this strategy provides an opportunity for TCM to play a more substantial role in PC treatment and in preventing further cancer progression.

Prostrate Cancer Prevalence and CAM usage

In Australia, the projected number of newly diagnosed cases of PC in 2015 is 17205.   PC represents a quarter of all male cancer and the projected number of deaths from PC in 2015 is 3440 (canceraustralia.com.au, 2015). In the last twenty-five years PC diagnosis has risen considerably in Australia and the rate of increase is greater than other comparable developed countries (Feletto et al., 2015). However, evidence suggests that although PC is a serious male health issue, the increasing prevalence appears to be due to the aging population and the increasing diagnostic use of the prostate specific antigen (PSA) (Armstrong & Lowe, 2014).

There is increasing evidence of the widespread use of CAM amongst PC patients. A population based study in Taiwan identified 22% of 972 PC patients used Chinese medicine, not including raw herbal medicine or patent products (Lin, Chen, & Chiu, 2011). A survey in America recorded 39% of 700 PC patients used some form of CAM, and although the survey results reported the CAM use did not improve treatment satisfaction, the high prevalence is noteworthy (Ramsey et al., 2012). A similar survey was undertaken in Adelaide, Australia. It reported a 50% usage of CAM for males with cancer who undertook the questionnaire. Although this figure included prayer and meditation, herbs and botanical products still represented 9.9% of participants (Klafke et al., 2011). These surveys did not provide a detailed analysis of the efficiency of CAM, however they were able to demonstrate the high number of cancer patients using CAM across a number of developed countries.

Common side effects of prostate cancer treatment

It is not unusual for PC treatment to involve a combination of bio medical modalities, often leading to complex strategies and multiple complications. For the purpose of this paper the following material is a brief mention of common PC treatment and associated side effects.

Prostatectomy

A radical prostatectomy (RP) is usually performed for men under the age of 65 who are considered a high risk of metastatic progression (Heidenreich et al., 2014). The most common and feared complications of an RP are urinary incontinence and impotence. The occurrence of urinary incontinence is often as high as 80% in patients, however a majority of patients experience improvements after time and therapeutic pelvic floor exercises (Michaelson et al., 2008). Erectile dysfunction can have a serious psychological impact on men, particularly when recovering from a prostate cancer diagnosis. Erectile dysfunction is often associated with feelings of guilt, shame and depression. Pelvic floor exercises and time can help, and medication in the form of PDE5 inhibiters is often used. These have a reasonable success rate but are also associated with side effects such as headaches, flushing and impaired vision (Partridge, 2011).

Androgen-deprivation therapy

Androgen-deprivation therapy is a common adjunct treatment after initial strategies have been applied for PC. For recurrent PC, ADT is often applied until death or for a substantial number of years (Michaelson et al., 2008). Non-surgical ADT involve the use of luteinizing hormone-releasing antagonists and more recently steroidal anti-androgen agents. These medications will act on the gonadptrophin by releasing hormones and thereby inhibiting testosterone and estrogen levels. This is an attempt to prevent cancer progression or maintain existing metastases (Heidenreich et al., 2014). Due to the hormonal interference and prolonged nature of ADT treatment there are various side effects of considerable concern. Hot flushing, loss of libido and gynaecomastia are common. These effects are not always causative but are often associated with depression and psychological distress, being another complication associated with ADT. Other serious complications include osteoporosis and cardiovascular disease such as myocardial infarction (Rhee et al., 2015).

Radiation therapy

There are two methods of applying radiation therapy for PC. These are external beam radiation therapy or more recently image-guided radiation therapy and interstitial brachytherapy or radioactive seed implantation. It is common to apply such treatments to low risk PC patients or in combination with ADT (Heidenreich et al., 2014). Similar to the previous mentioned treatments, radiation therapy can commonly cause urinary and erectile dysfunction. Erectile dysfunction can be a high as 40% after radiation therapy, commonly due to damage caused to the neurovascular bundles and penile bulb. However, due to the damage caused to local mucosal lining from radiation therapy, often symptoms are both more diverse and severe. Dysuria and hematuria are very common due to direct damage to the bladder(Michaelson et al., 2008). In addition, due to the close proximity to the prostate gland, damage to gastrointestinal tract is also common, the most prevalent conditions being proctitis and rectal urgency (Nam et al., 2014). 

Chemotherapy

Traditionally chemotherapy has not been a preferred option for PC treatment. However it still has relevance, particularly when the cancer has metastasized outside the prostate gland or there is a significant risk of metastasis occurring during a prostatectomy (Chopra & Rashid, 2015). Docetaxal is a commonly used chemotherapy PC drug. It is generally well tolerated, but is associated with side effects such as fluid retention, nail toxicity and myelosuppression (Baker et al., 2009).

Acupuncture providing supportive care for prostate cancer

For the intention of this paper three key complications of PC treatment and subsequent acupuncture treatments have been included.

Hot flushes

A literature review in 2010 spoke of the advances in oncology acupuncture. It discussed the benefits of acupuncture treatment for vasomotor symptoms in both breast cancer and prostate cancer. In fact, three acupuncture studies were cited for men with hot flushing due hormonal therapy. These were stated as being highly successful, particularly after several weeks of treatment (Lu & Rosenthal, 2010). However on closer inspection these studies do not present a high quality of evidence. The main limitation is small numbers of participants. One study that recorded a high success rate of acupuncture treatment had a participation group of 17, which ended in only 14 subjects completing the trial. At best this is only representative of a pilot study (Ashamalla, Jiang, Guirguis, Peluso, & Ashamalla, 2011). A systematic review for acupuncture treating hot flushes in men with prostate cancer concluded the current evidence was inconclusive. A majority of its included studies were observational and it stressed the need for adequately sized randomised control trials that adhere to current guidelines (Lee, Kim, Shin, Choi, & Ernst, 2009). A more recent and broad review of CAM therapies providing supportive care for advanced prostate cancer came to a similar conclusion regarding the treatment of hot flushes. They stated large randomised control trials (RCT) are necessary to enable acupuncture to be regarded as an effective treatment for prostate cancer patients with hot flushes (Scotté, 2012).

Erectile dysfunction

Men’s health, specifically impotence, has been a component of TCM treatment for hundreds of years. There are various texts that reveal TCM patterns and treatment strategies. Macioca’s writing is based on both his clinical experience and also classical literature such as the Yellow Emperor’s Classic Internal Medicine. He states impotence and erectile dysfunction are attributable to disharmony between the heart and kidney according to Chinese medicine pattern differentiation (Maciocia, 2013). However, there is minimal evidence to promote the efficacy of acupuncture for the treatment of erectile dysfunction due to prostate cancer treatment. In 2009 a systematic review for treating erectile dysfunction was completed. Although not exclusive to prostate cancer, this review included a thorough search of all aspects of erectile dysfunction (Lee, Shin, & Ernst, 2009). Currently this systematic review is in the process of being updated. It is the author’s intention to create a protocol for assessing the safety and effectiveness for acupuncture and the treatment of erectile dysfunction (Cui et al., 2015). However it is possible this review may be premature. For the purpose of this paper searching CINAHL, MEDLINE, PUBMED and Google Scholar databases, no recent or ongoing RCTs concerning erectile dysfunction were found.

Incontinence

Presently, there is more research available for use of acupuncture for urinary incontinence in women or during post stroke recovery (Song et al., 2013) (Liu et al., 2014). However, these studies do appear to be of a reasonable quality with promising results, which may encourage further research or treatment for incontinence after PC treatment. In 2010 a study compared the use of electro acupuncture with pelvic floor muscle therapy and the muscle therapy alone. The results stated initial improvement when both treatments were applied over the pelvic muscle therapy alone (Yang et al., 2010). However, further studies are needed to validate acupuncture as an effective treatment for urinary incontinence.

 Chinese herbal medicine providing supportive care for prostate cancer

A commonly known patented Chinese herbal formula for the treatment of prostate cancer is PC-SPES. It contains the following Chinese herbs: ju hua, ban lan gen, san qi, dong ling cao, ju zong lu, ling zhi and huang qin. Its actions are said to promote prostate health and strengthen the immune system (Dhooghe & Consortium, 2012).   Currently there is no strong evidence to suggest this product can effectively provide health benefits for PC patients. A crossover RCT trial did show some impressive results; however the trial was cancelled due to contaminates found in the product (Oh et al., 2004).   This lead to the product being withdrawn from the market and subsequent alternatives such as PC-SPES II. Currently there are further studies concerning PC-SPECS II, one being a pilot study with results not as positive as the initial study mentioned (Dhooghe & Consortium, 2012). Another, available in abstract only, has recorded PC-SPECS II providing cancer cell inhibition and the down regulation of the PSA (B. Y. Zhang, Li, Lai, Li, & Chen, 2015). Other evidence such as case reporting has suggested that PC- SPECS may interfere with the thyroid hormone and the production of sex hormones (Viswanathan & Vigersky, 2012). This may be of considerable concern with a patient undergoing ADT.

There has been considerable interest in single Chinese medicine herbs inhibiting the progression of PC. The strategy involves the targeting of molecular pathways, which promote cancer progression.   Although the particular interest in the herbs stems from their original medicinal usage, this treatment application does not align with TCM theory or pattern differentiation. Instead it represents a chemical extraction of particular botanicals and applying the extracts as treatment. Saussurea involucrate or xue lian has been involved in an in vitro research paper. It was determined the extract of this herb can inhibit PC3 cancer cell proliferation. However this paper also discussed the fact this herb is close to extinction and has a very slow growing rate which would provide limitations for further research and implantation of the medicinal on a grand scale (Way et al., 2010). Dan shen and yin chen hao are other Chinese herbs which have been evaluated for their PC cancer cell inhibition qualities. Tanshinones are isolated compounds of dan shen. A study found in vitro tanshinones were able to inhibit androgen receptors, thereby reducing the PSA and promote tumor regression (Y. Zhang et al., 2012). Scoparone, a compound of yin chen hao, was found to act against a specific prostate cancer cell aging in vitro and in mice (Kim et al., 2013). A common thread running though these compounded single herb studies is the lack of thorough biological understanding that creates the cellular and molecular anti-cancer effects. Perhaps the original comprehension of the herb from a traditional Chinese perspective could fill in the gaps here. Although these studies represent a lower level of research, according to the evidence hierarchy, they do promote interest and potentially justify the use of such herbs and further herbal formulation research.

A study in 2008 attempted to use a model more in line with the TCM pattern differentiation. It selected a base formula as the intervention and altered the formula according to variations in the participants’ TCM pattern. The results were favorable in that the intervention appeared to repress cancer cells and improve quality of life. However, this study did have limitations. The study had a small number of participants and was not an RCT, as it did not include a comparison group (Flaws, 2008). A more recent study compared a group of 71 PC patients with the TCM pattern of Qi deficiency and blood stagnation. They were randomized into two groups, one with a herbal formulated intervention with androgen therapy and the other group with androgen therapy and a placebo. After a period of four weeks, the treatment group showed improvements in the PSA and clinical symptoms when compared to the control group (Chen, Zhang, Wu, Yu, & Chang, 2013). This is a promising outcome from a well-designed study, which will potentially promote further research of a similar nature.

Can Traditional Chinese Medicine provide preventative treatment for prostate cancer?

Without clinical guidelines based on quantified research, using TCM as an adjunct to biomedical treatment for PC is faced with significant obstacles. The minimal evidence available will not encourage biomedicine to accept TCM as an effective treatment. In addition, the concern of drug and herb interaction is ever present from an oncologist’s perspective. One concern is interaction between herbs and antiestrogenic medication. For example, it has been postulated that dang gui has an interaction with estrogen (Lin et al., 2011). This issue is not exclusive to PC and currently there is not enough evidence to confirm or deny herb and hormonal interaction (Tsai, Lai, & Wu, 2014). These are serious limitations to applying TCM in combination with biomedical treatment. However, there is potential to apply TCM in some cases before biomedicine is implemented.

Another form of treatment currently applied to those diagnosed with abnormal or elevated PSA is active surveillance or ‘watchful waiting’ (Heidenreich et al., 2014). As mentioned earlier, the rates of diagnosis, particularly in elevated PSA in Australia, are on the rise. In Australia, guidelines are currently being determined in an attempt to provide appropriate support and treatment to patients while also reducing the overtreatment of low risk PC indicators (Armstrong & Lowe, 2014). As reported in America, the overtreatment of PC has significant financial cost and a greater likelihood of complications (Aizer et al., 2015). As the trend moves further towards ‘watchful waiting’, it is here TCM can be applied without any risk of drug interaction. Using pattern differentiation would allow TCM to treat a person in the hope of preventing further progression or cancer onset. As mentioned previously, TCM has a long history of treating cancer. The prostate primarily concerns the liver and kidneys in TCM, though the small intestine and the heart can also play a role (Lahans, 2007). An imbalance in these organs, whether it is stagnancy or a pattern of depletion, will represent the earliest of onset of PC. It would be fascinating to design an RCT with all participants within an active surveillance group implementing a TCM intervention of Chinese herbal medicine and/or acupuncture. The non-treatment group could be given lifestyle advice such as nutrition and exercise to satisfy ethical issues. A favorable outcome would be achieved if the early implementation of TCM could reduce potential complications and the need for further biomedical treatment.

Conclusion

Current evidence is insufficient to advocate the use of acupuncture or Chinese herbal medicine as an effective treatment for complications of PC. However, recent research has shown positive outcomes or points of interest that highlights the need for further research. If detected early, PC patients are often recommended to wait and watch, rather than undergo any invasive treatment. This ‘watchful waiting’ provides TCM with an opportunity to intervene and prevent further onset or progression of PC.

References

Aizer, A. A., Gu, X., Chen, M. H., Choueiri, T. K., Martin, N. E., Efstathiou, J. A., . . . Nguyen, P. L. (2015). Cost implications and complications of overtreatment of low-risk prostate cancer in the United States. J Natl Compr Canc Netw, 13(1), 61-68.

Armstrong, B. K., & Lowe, A. P. (2014). Clinical practice guidelines for PSA testing and early management of test-detected prostate cancer. Paper presented at the Cancer Forum.

Ashamalla, H., Jiang, M. L., Guirguis, A., Peluso, F., & Ashamalla, M. (2011). Acupuncture for the alleviation of hot flashes in men treated with androgen ablation therapy. International Journal of Radiation Oncology* Biology* Physics, 79(5), 1358-1363.

Baker, J., Ajani, J., Scotté, F., Winther, D., Martin, M., Aapro, M. S., & von Minckwitz, G. (2009). Docetaxel-related side effects and their management. European Journal of Oncology Nursing, 13(1), 49-59. doi:http://dx.doi.org/10.1016/j.ejon.2008.10.003

canceraustralia.com.au. (2015). http://canceraustralia.gov.au/affected-cancer/cancer-types/prostate-cancer/prostate-cancer-statistics.

Chen, D., Zhang, P., Wu, T., Yu, X., & Chang, D. (2013). Clinical effects of qilan capsule combined with androgen deprivation therapy on the treatment of prostate cancer (Deficiency of Qi and blood stasis type). [Chinese]. Chinese Journal of Andrology, 27(6), 19-22. Retrieved from http://ezproxy.uws.edu.au/login?url=http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed12&AN=2014585559

Chopra, S., & Rashid, P. (2015). Management of castration-resistant (advanced) prostate cancer (CRPC): Rationale, progress and future directions. Australian Family Physician, 44(5), 302.

Cui, X., Li, X., Peng, W., Zhou, J., Yu, J., Ye, Y., & Liu, Z. (2015). Acupuncture for erectile dysfunction: a systematic review protocol. BMJ open, 5(3), e007040.

Dhooghe, L., & Consortium, C.-C. (2012). PC-SPES.

Feletto, E., Bang, A., Cole-Clark, D., Chalasani, V., Rasiah, K., & Smith, D. (2015). An examination of prostate cancer trends in Australia, England, Canada and USA: Is the Australian death rate too high? World journal of urology, 1-11.

Flaws, B. (2008). A study on the integrated Chinese-Western medical treatment of Prostate cancer. Townsend Letter, Aug-Sept(Academic OneFile).

Heidenreich, A., Bastian, P. J., Bellmunt, J., Bolla, M., Joniau, S., van der Kwast, T., . . . Zattoni, F. (2014). EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. European urology, 65(2), 467-479.

Kim, J.-K., Kim, J.-Y., Kim, H.-J., Park, K.-G., Harris, R. A., Cho, W.-J., . . . Lee, I.-K. (2013). Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity.

Klafke, N., Eliott, J., Wittert, G., & Olver, I. (2011). Prevalence and predictors of complementary and alternative medicine (CAM) use by men in Australian cancer outpatient services. Annals of Oncology, mdr521.

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Lee, M. S., Kim, K.-H., Shin, B.-C., Choi, S.-M., & Ernst, E. (2009). Acupuncture for treating hot flushes in men with prostate cancer: a systematic review. Supportive care in cancer, 17(7), 763-770.

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Lin, Y.-H., Chen, K.-K., & Chiu, J.-H. (2011). Coprescription of Chinese herbal medicine and Western medications among prostate cancer patients: a population-based study in Taiwan. Evidence-Based Complementary and Alternative Medicine, 2012.

Liu, B., Wang, Y., Xu, H., Chen, Y., Wu, J., Mo, Q., & Liu, Z. (2014). Effect of electroacupuncture versus pelvic floor muscle training plus solifenacin for moderate and severe mixed urinary incontinence in women: a study protocol. BMC complementary and alternative medicine, 14(1), 301.

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Maciocia, G. (2013). Diagnosis in Chinese medicine: a comprehensive guide: Elsevier Health Sciences.

Michaelson, M. D., Cotter, S. E., Gargollo, P. C., Zietman, A. L., Dahl, D. M., & Smith, M. R. (2008). Management of complications of prostate cancer treatment. CA: a cancer journal for clinicians, 58(4), 196-213.

Nam, R. K., Cheung, P., Herschorn, S., Saskin, R., Su, J., Klotz, L. H., . . . Kodama, R. T. (2014). Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study. The Lancet Oncology, 15(2), 223-231.

Oh, W. K., Kantoff, P. W., Weinberg, V., Jones, G., Rini, B. I., Derynck, M. K., . . . Rosen, R. T. (2004). Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer. Journal of Clinical Oncology, 22(18), 3705-3712.

Partridge, C. (2011). Erectile dysfunction following radical prostatectomy: a review of current treatment options.

Ramsey, S. D., Zeliadt, S. B., Blough, D. K., Fedorenko, C. R., Fairweather, M. E., McDermott, C. L., . . . Arora, N. K. (2012). Complementary and alternative medicine use, patient-reported outcomes, and treatment satisfaction among men with localized prostate cancer. Urology, 79(5), 1034-1041. Retrieved from http://ezproxy.uws.edu.au/login?url=http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed10&AN=2012249215

Rhee, H., Gunter, J. H., Heathcote, P., Ho, K., Stricker, P., Corcoran, N. M., & Nelson, C. C. (2015). Adverse effects of androgen?deprivation therapy in prostate cancer and their management. BJU international, 115(S5), 3-13.

Scotté, F. (2012). The importance of supportive care in optimizing treatment outcomes of patients with advanced prostate cancer. The oncologist, 17(suppl 1), 23-30.

Song, F., Jiang, S., Zheng, S., Ye, T., Zhang, H., Zhu, W., . . . Liu, X. (2013). [Electroacupuncture for post-stroke urinary incontinence: a multi-center randomized controlled study]. Zhongguo zhen jiu= Chinese acupuncture & moxibustion, 33(9), 769-773.

Tsai, Y.-T., Lai, J.-N., & Wu, C.-T. (2014). The use of Chinese herbal products and its influence on tamoxifen induced endometrial cancer risk among female breast cancer patients: A population-based study. Journal of ethnopharmacology, 155(2), 1256-1262.

Viswanathan, L., & Vigersky, R. A. (2012). The effect of herbal medications on thyroid hormone economy and estrogen-sensitive hepatic proteins in a patient with prostate cancer. Archives of internal medicine, 172(1), 58-60.

Way, T.-D., Lee, J.-C., Kuo, D.-H., Fan, L.-L., Huang, C.-H., Lin, H.-Y., . . . Liu, H. (2010). Inhibition of epidermal growth factor receptor signaling by Saussurea involucrata, a rare traditional Chinese medicinal herb, in human hormone-resistant prostate cancer PC-3 cells. Journal of agricultural and food chemistry, 58(6), 3356-3365.

Yang, B., Ye, D., Yao, X., Peng, J., Zhang, S., Dai, B., . . . Zhu, Y. (2010). [The study of electrical acupuncture stimulation therapy combined with pelvic floor muscle therapy for postprostatectomy incontinence]. Zhonghua wai ke za zhi [Chinese journal of surgery], 48(17), 1325-1327.

Zhang, B. Y., Li, Y. F., Lai, Y., Li, Y. S., & Chen, Z. J. (2015). [Effect of compound Chinese traditional medicine PC-SPES II in inhibiting proliferation of human prostate cancer cell LNCaP and on expressions of AR and PSA]. Zhongguo Zhong Yao Za Zhi, 40(5), 950-956.

Zhang, Y., Won, S.-H., Jiang, C., Lee, H.-J., Jeong, S.-J., Lee, E.-O., . . . Lü, J. (2012). Tanshinones from Chinese medicinal herb Danshen (Salvia miltiorrhiza Bunge) suppress prostate cancer growth and androgen receptor signaling. Pharmaceutical research, 29(6), 1595-1608.

 

Published on February 2, 2016