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Top ten myths about prostate cancer in India

Robert Anton Wilson once said,

“Humans live through their myths and only endure their realities.”. Its time we busted the top ten myths about prostate cancer in India and uncover the reality we have to endure in the clinic every day.

MYTH #10

Prostate cancer is rare in India

WRONG!

2009–2011 National Cancer Registry Program reports, from twenty five population-based cancer registries across India shows that prostate cancer is ranked among top ten in all the regions[1]. Incidence rates are quite higher in Delhi compared to other parts of India and it is rapidly increasing. Presently it is the second leading anatomical site of cancer in Delhi. The situation is no different in other regions. In Kolkata and Trivandrum it is the second most common, and in Mumbai, it is the 3rd most common site of cancer. Rare? Not even close to it.

MYTH #9

Bilateral orchidectomy is a good treatment for most prostate cancer patients

WRONG!

Hormonal therapy for localized prostate cancer is not recommended in isolation. These patients have a potential for cure, long life expectancy, and every effort must be made to avoid the adverse effects of long-term androgen deprivation. The 10 year survival after radical prostatectomy in localized prostate cancer exceeds 95%[2]. Bilateral orchiectomy in these patients is not curative, and increases the morbidity. Radical prostatectomy is treatment of choice for most patients with organ confined prostate cancer with a life expectancy greater than 10-15 years. Even in high risk and locally advanced prostate cancer, radical prostatectomy can achieve good cancer specific and overall survival[3, 4], especially when treated with adjuvant/salvage radiotherapy and/or androgen deprivation therapy.

MYTH #8

Androgen Deprivation Therapy has minimal side effects

WRONG!

Besides the expected adverse effects of hot flashes, loss of libido, sexual dysfunction, osteoporosis (and associated skeletal events), ADT is associated with a high cardiovascular risk, myocardial infarction, sudden cardiac death (especially in patients with history of recent cardiovascular disease and especially within 6 months of starting ADT[5][6], significantly higher risk of ischemic stroke[7] and even diabetes[8], hyperlipidemia and obesity (metabolic syndrome)[9] The U.S. FDA has notified the manufacturers of GnRH agonists to add a warning on the drug label about increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men receiving these medications for the treatment of prostate cancer.[10]

MYTH #7

Finger guided / Six core biopsy is sufficient for diagnosing prostate cancer

WRONG!

Six core biopsy is no longer considered adequate in detecting prostate cancer. It has a very high false negative rate of 15-34% (which increases the chance of a repeat biopsy)[11]. 10-12 core biopsies increase the cancer detection rate by 31%[12]. Increasing the number of cores further increases the CDR only marginally. Moreover, increasing the number of cores improves biopsy concordance with prostatectomy specimens. Concordance rates of prostate cancer grade, when an extended biopsy scheme is used, are as high as 85%, compared to 50% with a sextant biopsy[13, 14]. There is no significant difference in detection rate of insignificant cancer between sextant and 12 core biopsy[15]

MYTH #6

Biochemical recurrence after primary treatment is a death sentence for the patient

WRONG!

The median time to metastases after biochemical failure, if left untreated is 8 years![16] The 10 year overall survival is 62%.  After salvage radiotherapy, overall survival rises to 86%[17] and disease free survival at 6 years is 32%. Nomograms can predict which patients will progress, and nadir PSA is an important determinant of disease free survival. In patients who achieve a nadir PSA of <0.5 ng/ml, the disease free survival at 6 years is 50%[18]. All this doesn’t sound like a death sentence. A life on a hospital parole would be a better way to describe it.

MYTH #5

Radical prostatectomy should not be done in patients who have already undergone a TURP

WRONG!

Although post TURP radical prostatectomy may be more challenging with higher blood loss and higher rate of complications, there is no significant difference in oncologic efficacy[19]. Robotic surgery has a unique role in these patients. Intraoperative blood loss, post operative complications, duration of catheterization and hospital stay may be reduced by doing a robot assisted surgery[20]. These cases are challenging, operative time is longer when compared with patients without previous prostate surgery, and should be handled by robotic surgeons with appropriate expertise[21].

MYTH #4

Lifestyle management has a minimal role in prostate cancer patients

WRONG!

Metastatic prostate cancer patients are at a higher risk of skeletal related events and osteoporosis. Besides calcium and vitamin D supplementation and 1 to 3 monthly zoledronic acid injections, weight-bearing exercise helps maintain bone health in ca prostate.

Localized prostate cancer patients on a low-fat, vegan diet, exercise, and stress management have significantly high quality of life scores, better physical, mental and sexual function[22]. There is also some preliminary evidence to suggest that avoidance of smoking and establishing a regular exercise regimen may decrease the chances of prostate cancer recurrence after primary treatment[23, 24].

MYTH #3

Calcium and vitamin D supplementation is adequate to preserve bone strength in patients on ADT

WRONG!

The widely quoted Zometa 039 trial randomized 643 men with CRPC and asymptomatic or minimally symptomatic bone mets to calcium and vitamin D supplementation with intravenous zoledronic acid (4 or 8 mg every 3 weeks) or calcium and vitamin D supplementation alone. Zoledronic acid group had significantly less skeletal related events as well as increased median survival[25]. NCCN guidelines for mCRPC recommend zoledronic acid 4 mg intravenously every 3-4 weeks. Although there is no consensus on the frequency of zoledronic acid, the WHO has developed a fracture risk assessment model (FRAX) which can be assessed in every case, and a baseline DEXA scan to assess bone mineral density should be done in every case. Based on the finding of FRAX score and DEXA scan, recommendations can be tailored to individual patient. For CRPC, denosumab was compared to zoledronic acid and was found to be better at reducing skeletal events and therefore may be preferable to zoledronic acid[26]. Denosumab can also increase bone mineral density and is the only agent approved for this condition[27]. Calcium and vitamin D supplementation does form an essential part of bone health program in prostate cancer patients, but supplementation alone may be inadequate for many.

MYTH #2

Chemotherapy is indicated only for castrate resistant prostate cancer

WRONG!

Till recently, chemotherapy was thought to be indicated only after progression despite hormone therapy. This concept has recently been challenged. Docetaxel may act as a hormonal agent, interfering with androgen receptor (AR) nuclear translocation on microtubules[28]. In the E3805 study (CHAARTED trial) conducted by the National Cancer Institute, addition of docetaxel to ADT in hormone naive newly diagnosed metastatic prostate cancer patients improved overall survival by more than 13 months. The benefit was even more in high volume disease. The median time to clinical progression also improved from 19.8 months in the androgen-deprivation therapy alone group vs 32.7 months in the androgen-deprivation therapy plus docetaxel group which was statistically significant[29]. The UK based STAMPEDE trial has also confirmed these findings[30]. The magnitude of advantage (13 months of survival advantage) has been unprecedented – more than any other therapy in the past!

MYTH #1

Robotic surgery does not improve functional outcomes of radical prostatectomy

WRONG!

Robot assisted radical prostatectomy is associated with improved surgical margin status relative to Open radical prostatectomy for intermediate and high-risk disease and less use of postprostatectomy ADT and RT[31]. This may be attributed to better visualization of the prostate capsule and apex during robot-assisted laparoscopic surgery secondary to 􏰃10X magnification, fiber-optic illumination, and CO2 insufflation that tamponades venous blood loss compared with open surgery. These technical advantages have an impact on functional outcomes as well. Systematic review of 51 articles reporting continence rates after robotic prostatectomy revealed a statistically significant better continence at 12 months after robot assisted surgery[32]. A similar systematic review of studies reporting potency rates after surgery showed a significant advantage in favor of robot assisted surgery[33]. Blood loss and transfusion was also significantly less in robot assisted surgery.

Enough evidence to make it the number 1 in this list!!

 

Bibliography

1. Jain, S., S. Saxena, and A. Kumar, Epidemiology of prostate cancer in India. Meta Gene, 2014. 2: p. 596-605.

2. Mendhiratta, N., et al., 10-year Mortality After Radical Prostatectomy for Localized Prostate Cancer in the Prostate Specific Antigen Screening Era. Urology, 2015.

3. Milonas, D., et al., Outcome of surgery in locally advanced pT3a prostate cancer. Cent European J Urol, 2011. 64(4): p. 209-12.

4. Sood, A., et al., Role of robot-assisted radical prostatectomy in the management of high-risk prostate cancer. Indian J Urol, 2014. 30(4): p. 410-7.

5. O’Farrell, S., et al., Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer. J Clin Oncol, 2015. 33(11): p. 1243-51.

6. Keating, N.L., et al., Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst, 2012. 104(19): p. 1518-23.

7. Teoh, J.Y., et al., Risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population living in Hong Kong. Jpn J Clin Oncol, 2015. 45(5): p. 483-7.

8. Nagarajan, S., R. Cherian, and A.S. Balasubramanian, A heterogeneous beta-D-glucosidase activator from monkey parotid gland and its use as an affinity ligand in the purification of human salivary beta-D-glucosidase. Biochem Int, 1987. 14(2): p. 365-73.

9. Gunnarsson, O., S. Basaria, and G.A. Gignac, Cardiometabolic and skeletal risk factors in black men with prostate cancer starting androgen deprivation therapy. Cancers (Basel), 2015. 7(2): p. 679-87.

10. Administration, U.S.F.a.D. FDA Drug Safety Communication: Update to Ongoing Safety Review of GnRH Agonists and Notification to Manufacturers of GnRH Agonists to Add New Safety Information to Labeling Regarding Increased Risk of Diabetes and Certain Cardiovascular Diseases. 2010  [cited 2015 11-08-2015]; Available from: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm.

11. Levine, M.A., et al., Two consecutive sets of transrectal ultrasound guided sextant biopsies of the prostate for the detection of prostate cancer. J Urol, 1998. 159(2): p. 471-5; discussion 475-6.

12. Babaian, R.J., et al., A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol, 2000. 163(1): p. 152-7.

13. San Francisco, I.F., et al., Extended prostate needle biopsy improves concordance of Gleason grading between prostate needle biopsy and radical prostatectomy. J Urol, 2003. 169(1): p. 136-40.

14. Mian, B.M., et al., Role of prostate biopsy schemes in accurate prediction of Gleason scores. Urology, 2006. 67(2): p. 379-83.

15. Meng, M.V., et al., Impact of increased number of biopsies on the nature of prostate cancer identified. J Urol, 2006. 176(1): p. 63-8; discussion 69.

16. Pound, C.R., et al., Natural history of progression after PSA elevation following radical prostatectomy. JAMA, 1999. 281(17): p. 1591-7.

17. Trock, B.J., et al., Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA, 2008. 299(23): p. 2760-9.

18. Stephenson, A.J., et al., Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol, 2007. 25(15): p. 2035-41.

19. Menard, J., et al., Laparoscopic radical prostatectomy after transurethral resection of the prostate: surgical and functional outcomes. Urology, 2008. 72(3): p. 593-7.

20. Martinschek, A., et al., Radical prostatectomy after previous transurethral resection of the prostate: robot-assisted laparoscopic versus open radical prostatectomy in a matched-pair analysis. J Endourol, 2012. 26(9): p. 1136-41.

21. Gupta, N.P., P. Singh, and R. Nayyar, Outcomes of robot-assisted radical prostatectomy in men with previous transurethral resection of prostate. BJU Int, 2011. 108(9): p. 1501-5.

22. Daubenmier, J.J., et al., Lifestyle and health-related quality of life of men with prostate cancer managed with active surveillance. Urology, 2006. 67(1): p. 125-30.

23. Kenfield, S.A., et al., Smoking and prostate cancer survival and recurrence. JAMA, 2011. 305(24): p. 2548-55.

24. Kenfield, S.A., et al., Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol, 2011. 29(6): p. 726-32.

25. Saad, F., et al., A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst, 2002. 94(19): p. 1458-68.

26. Fizazi, K., et al., Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet, 2011. 377(9768): p. 813-22.

27. Smith, M.R., et al., Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med, 2009. 361(8): p. 745-55.

28. Thadani-Mulero, M., et al., Androgen receptor splice variants determine taxane sensitivity in prostate cancer. Cancer Res, 2014. 74(8): p. 2270-82.

29. Sweeney, C.J., et al., Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med, 2015.

30. Nicholas David James, M.R.S., Malcolm David Mason, Noel W. Clarke, David Paul Dearnaley, Melissa Ruth Spears, et al, Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: First overall survival results from STAMPEDE (NCT00268476). in 2015 ASCO annual meeting. 2015, American society of Clinical Oncology: Chicago. p. abstr 5001.

31. Hu, J.C., et al., Comparative effectiveness of robot-assisted versus open radical prostatectomy cancer control. Eur Urol, 2014. 66(4): p. 666-72.

32. Ficarra, V., et al., Systematic review and meta-analysis of studies reporting urinary continence recovery after robot-assisted radical prostatectomy. Eur Urol, 2012. 62(3): p. 405-17.

33. Ficarra, V., et al., Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol, 2012. 62(3): p. 418-30.

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