Case Report: A castration-resistant terminal prostate cancer

Most metastatic prostate cancer patients receive androgen Background: deprivation therapy (ADT) as the mainstay of treatment. Unfortunately, patients ultimately progress to castration resistance. We describe a man in his eighties who Clinical finding and diagnosis: developed stage IV, M1b prostate cancer, and multiple (≥5) bone metastases who required the aid of a walker to ambulate. Without treatment, his treating physician predicted he would survive 6 months. The patient initially responded well to Interventions and outcomes: treatment with ADT, but during the 80-89th week of treatment he developed castration resistance. ADT was then discontinued. He subsequently began practicing Falun Gong (FLG) as an alternative form of care. Within one year of constant practice, he became able to walk independently, his bone metastases disappeared, and he also enjoyed better psychosocial functioning. His treating physician assessed that his prostate malignancy was “clinically, under control” and “his overall functional status is excellent.” The patient survived a total of 263 weeks (61.4 months) post diagnosis, including 174 weeks (40.6 months) after developing castration resistance. This castration-resistant terminal prostate cancer patient Conclusion: gained significant clinical benefits after practicing Falun Gong.


Introduction
Prostate cancer is the second most common cancer a and the fifth leading cause of cancer death in men b worldwide. In the United States, it is the most prevalent cancer and the second leading cause of cancer death in men c . The five-year overall survival in metastatic prostate cancer patients aged ≥ 75 years is 13.6% 1 . Androgen deprivation therapy (ADT), either by means of bilateral orchiectomy or the administration of a gonadotropinreleasing hormone (GnRH) agonist or antagonist, is the mainstay of treatment for metastatic prostate cancer 2 . In most metastatic prostate cancer patients, ADT is initially effective, but its response is not sustained and patients ultimately progress to castration resistance 3 .
In recent years there has been a growing awareness of oriental meditative approaches for health and wellness in the West. Deeply rooted in thousands of years of Chinese cultural history, Qigong is a traditional Chinese mind-body practice that uses qi (vital energy) and consciousness cultivation to achieve an optimal health state. Falun Gong (FLG) is a unique type of ancient qigong practice based on the principles of "truthfulness-compassion-tolerance". The practice of FLG includes reading the main teachings, Zhuan Falun d and performing five sets of slow, gentle, meditative exercises e .
Recently, we prospectively followed a terminal stage IV prostate cancer patient in his eighties, who relapsed after ADT and then began practicing FLG. This is the first well documented castration-resistant prostate cancer case whose survival was significantly prolonged after practicing FLG.

Case report
An 80-year-old Chinese man was a retired professor at a university in the USA. He presented to a urology clinic in 2014 complaining of bone pain, fatigue, and an elevated prostate specific antigen (PSA; ranging from 94.7 to 126.6 ng/ml; normal range: 0.6-12.4 ng/ml for 75-79 years born in China 4 ) for one year. He had a 20-year history of hypothyroidism treated with Synthroid™ (75µg/day), a hernia operation in 2003, and an implanted pacemaker in 2011. He had been diagnosed with benign prostate hyperplasia in 2004 and his baseline PSA values ranged from 4.1 to 8.6 ng/ml between 1996 and 2006. There was a family history of cancer. The patient required the aid of a walker to ambulate. Digital rectal exam (DRE) revealed a "very hard, very nodular and fixed prostate." PSA was 468 ng/ml on presentation. Transrectal ultrasound image showed the prostate to be 63×57×53 mm 3 with disrupted capsule, abnormal inhomogeneous peripheral zone, scattered calcifications, and no median lobe. The prostate biopsy pathology report revealed an adenocarcinoma with a Gleason Score 9 (4+5 or 5+4) in all lobes with 40-80% cancer infiltration ( Figure 1). Whole-body bone scan was highly suspicious for numerous osseous metastases in the lumbar and thoracic spine as well as in the left iliac bone of the pelvis, some areas of the sacrum and in the left 9th rib (Figure 2). CT scan findings were consistent with the bone scan ( Figure 2). The patient was diagnosed with terminal stage IV, M1b metastatic prostate adenocarcinoma with extensive (≥5) bone metastases. His treating physician predicted that without effective treatment he would have a life expectancy of only 6 months.
The patient was started on degarelix (240mg, 80mg, 80mg at month intervals) and bicalutamide 50mg daily. Survival was monitored by symptoms and serum PSA. Quality of life (QoL) was assessed with the SF-8™ questionnaire (Table 1). Psychosocial functioning was evaluated using an adapted, simplified six-part questionnaire that assessed the patient's status of positive thinking, happiness, altruism, emotional control and purpose of life. All these parameters have been systemically researched in a number of mindfulness psychological studies and commonly used in psychosocial functioning outcomes 5 ( Table 2). a http://gco.iarc.fr/today/online-analysis-pie?v=2018&mode=cancer&mo de_population=continents&population=900&populations=900&key=tot al&sex=1&cancer=39&type=0&statistic=5&prevalence=0&population_ group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_ i t e m s = 7 & g r o u p _ c a n c e r = 1 & i n c l u d e _ n m s c = 1 & i n c l u d e _ n m s c _ other=1&half_pie=0&donut=0&population_group_globocan_id= b http://gco.iarc.fr/today/online-analysis-pie?v=2018&mode=cancer&mo de_population=continents&population=900&populations=900&key=tot Figure 1. Core biopsy of the patient's prostatic adenocarcinoma (hematoxylin and eosin stain). The adenocarcinoma consists of poorly formed or fused glandular acini (Gleason grade 4) and aggregates, cords and solid foci not recognizable as acini (Gleason grade 5), resulting in the Gleason score of 9 (4+5). The Gleason score is the sum of two most prevalent histologic grades in a prostate adenocarcinoma, rated on a scale of 1-5, with 5 being the most clinically aggressive.  The patient's bone pain was gone within 5 days. After five weeks, his PSA dropped to 4.5 ng/ml. At week 14, degarelix was replaced with leuprolide acetate at a dose of 22.5 mg quarterly. PSA levels remained at 0-0.2 ng/ml until week 68. At week 80, his PSA rose to 1.4 ng/ml, and his physician discontinued bicalutamide due to suspicion of cancer relapse. PSA continued to increase to 2.4 ng/ml at week 84 and to 3.7 ng/ml at week 89. (Figure 3, Table 3) The physician planned to use abiraterone acetate plus prednisone or enzalutamide if the PSA rose to 10 ng/ml. The patient was not pleased with either choice because of the increased risk of side effects and limited survival benefits. ADT was then discontinued. At week 89, the patient began practicing FLG. When he watched the FLG video for the first time, the patient reported that he felt as if substantial high energy matter was plugged into his two lower legs. He could sense the flow of energy and the warmth induced by the energy during practicing. In the past, during cold winter nights, the patient had a tendency to get cramps in his legs. To prevent this, he had been using a hot water bottle under the quilt while sleeping for many years. Soon after starting to practice FLG, the patient reported he did not need a hot water bottle anymore.
At week 94, the patient's PSA reversed its increasing trend by dropping to 0.6 ng/ml ( Figure 3, Table 3). At week 106, he no longer needed the assistance of a walker. At weeks 130 and 133, no osseous metastases were seen on either CT or whole-body bone scan ( Figure 2). At week 151, DRE revealed that the prostate was softer and smaller than before.
Following ADT, the patient experienced adverse events including right foot swelling, wheezing, and hot flashes for about one year, all of which, the patient reported, had gradually disappeared after practicing FLG.
The patient's QoL improved greatly with FLG practice (Table 1). He was even able to go up a 14-step stairway without stopping halfway or developing shortness of breath with exertion on stairs he had before practicing FLG (Extended data: Video S1). Additionally, the patient reported the following sequential trend of psychosocial functioning improvement: starting FLG practice, finding the purpose of life, developing positive thinking, having a better temperament, experiencing symptom improvement, feeling happier and less depressed, and becoming more altruistic (Table 2). At week 219, based on the extended survival, absence of symptoms, disappearance of bone  * After onset of cancer and before practicing FLG, the patient was short of breath after climbing a 14-step staircase and had to rest midway to catch his breath. At week 187, he could go up the same 14-step staircase without stopping halfway and was no longer short of breath after reaching the top.      Needed a walker to ambulate.  metastases, improved QoL and psychosocial functioning, his treating physician assessed that his prostate malignancy was "clinically, under control" and "his overall functional status is excellent." The patient reported to be living a healthy life with good physical and mental status. He shared his experience as a terminal cancer survivor in the hospital support group as well as with the local medical community.
On week 228, the patient had a car accident which resulted in a severe neck injury and decreased ability to walk. On week 263, the patient was found dead at home from unknown causes. Three days before his death, he had spoken with us and denied any signs or symptoms of cancer relapse.

Discussion
The While there are anecdotical testimonies from terminal cancer patients revealing they survived longer than expected after practicing FLG 8,9 , this is the first case report documented with detailed medical records. According to the canon of traditional Chinese medicine, the Yellow Emperor's Classic of Medicine, people may enjoy a long, disease-free life by cultivating the mind and following upright moral principles 10 . The emerging discipline of psychoneuroimmunology has begun to disclose the relationship between psychological, neurological and immunological systems. For example, eudaimonic well-being is found to be associated with decreased expression of transcriptional response to adversity profile involving inflammation mediated neoplastic diseases 11 , decreased tumour growth and progression-related norepinephrine 12 . The patient presented here experienced symptom improvement soon after reading Zhuan Falun and accepting the principles of "truthfulnesscompassion-tolerance", suggesting that the improvement of moral and spiritual character also plays a significant role in the improvement of health.

Conclusions
We describe in detail for the first time in the medical literature, the clinical course of a terminal prostate cancer case with relapse to ADT followed by FLG practice, an ancient Qigong practice originating from China. Most of the patient's prostate cancer signs and symptoms disappeared quickly after FLG practice, accompanied with greatly improved psychosocial functioning and quality of life. We conclude that this terminal prostate cancer case gained clinical benefits through practicing FLG. Although the mechanism by which FLG practice caused improvement is not yet well understood, its effects are identifiable and measurable. Thus, the practice of FLG deserves more investigation by the medical community.

Patient perspective
"My name is XXX. I had a teaching career as an Organic Chemistry Professor for 37 years at XXX before retiring in 2000. In May of 2014, I became a final stage, metastatic prostate cancer patient with bone pain, a 468 PSA, and an estimated life expectancy of less than half a year. I also required the aid of a walker to ambulate. After 19 months of androgen deprivation therapy (ADT), my cancer relapsed. Shortly prior to that relapse, I was very fortunate to have discovered a relatively new but rapidly growing mind and body cultivation practice known as Falun Gong that came originally from China.

Consent
Written informed consent for the publication of this case report and any associated images was obtained from the patient before his death.

Data availability
Underlying data All data underlying the results are available as part of the article and no additional source data are required. however, is commonly observed in the practice of FLG.

Extended data
(2) In the absence of serum testosterone levels after ADT was stopped, the case is not convincing. Answer: In Table 3, serum testosterone levels were tested at 44, 31, <3 and <3 (ng/dL) at week 1, 5, 84 and 89, respectively. Testosterone levels dropped quickly at the beginning of ADT and stayed low (<3 ng/dL) after discontinuing antiandrogen at week 84 and 89, as expected with the use of the LHRH agonist. However, PSA levels progressively rose between week 68 (0.2 ng/ml) and week 89 (3.7 ng/ml) despite low testosterone, indicating the cancer had become resistant to ADT. Thus, the testosterone level was not considered to have any role in the subsequent clinical events.
(3) "Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?" "Is the case presented with sufficient detail to be useful for other practitioners?" The reviewer ticked "no" to both questions. Answer: Based on this case's well documented hospital records, we have provided adequate physical examinations, diagnostic tests (biopsy, PSA levels, testosterone levels, bone scan, CT scan), details of the treatments given, as well as the clinical outcomes. We believe this case report has been presented with ample medical details. Clinical physicians and patients are likely to appreciate the significance of this case study's findings, especially if they consider the following three perspectives: I. Survival Such a significantly prolonged survival time is rarely reported in the medical literature and should be of great interest for those physicians who has managed similar patients. In the CHAARTED trial, a high volume of metastatic prostate cancer was defined by the presence of visceral metastases or four or more bone lesions with at least one beyond the vertebral bodies and pelvis 5 . This 80-year-old patient with a Gleason score of 9 met the definition of high volume metastatic prostate cancer as he had 5 bone metastases including one site beyond the vertebral body and pelvis (left 9th rib region). In the CHAARTED trial, the median life expectancy for an analogous patient was 32.2 months with patients seldom surviving longer than 60 months. Despite the multiple effective treatment for castration resistant prostate cancer, such as chemotherapy and second-generation anti-androgen therapy (zytiga, xtandi), provided by in this large clinical trial, the median life expectancy was just 32.2 months. In the non-academic medical community, the median life expectancy may be even shorter, perhaps around 27 months 6 . The patient in this study, who practiced FLG, survived a total of 61.4 months (263 weeks) post-diagnosis, which is longer than comparable patients in both the CALGB 9583 and CHAARTED studies. II. Quality of life Without any effective drug treatment options after developing castration resistance, the patent in this case lived without any symptoms, in excellent mental and spiritual health, with a good quality of life, without any cancer complications (such as bone pain, skeletalrelated events, and urinary symptoms), or medication side effects. We believe that this case has been presented with sufficient evidence of the valuable clinical benefits this patient experienced from practicing FLG. This information is useful for physicians and patients alike who are searching for effective treatment options. III. Cost FLG practice is free, and anyone can start or stop the practice on his own. This may alleviate physicians and patients' financial concerns.
The patient himself was a rigorous scientist who received orthodox scientific training and had a very good reputation in the organic chemistry community. His personal experience of practicing Falun Gong made him realize that "there may very well be a set of supernormal science on human body that is quite unique, subtle, and highly deserving of greater attention and further studies by modern scientists." We appreciate Dr. Klotz's comments and hope this response answers his questions and concerns properly.
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