Introduction

Prostate cancer is the most frequently occurring cancer among men. The widespread use of the prostate specific antigen test (PSA) in recent years has resulted in dramatic increases in the number of men diagnosed at both a younger age and at an earlier stage of the disease. Consequently, the number of men seeking treatment for localized prostate cancer has also increased, suggesting that more men are living with possible long-term side effects of prostate cancer treatment. Evidence to date has yet to show a clear survival advantage for any given treatment of early-stage or localized prostate cancer. While potentially curative, existing treatments such as radiotherapy (external or 3-Dimensional conformal beam)), surgery (Radical Prostatectomy), or radioactive seed implantation (Brachytherapy) can also have side-effects that can impact quality of life among prostate cancer survivors.
The following is a review of the current Quality-of-life (QOL) studies evaluating the three most common treatments for localized prostate cancer: Radical prostatectomy (surgical removal of the prostate), external radiation, and brachytherapy (radioactive seed implants).

Quality-of-Life after Radical Prostatectomy

Radical prostatectomy (surgical removal of the prostate) is the most common treatment for early stage prostate cancer and provides an effective cure in most cases. However, temporary urinary incontinence and more durable (and often permanent) difficulty attaining erections (erectile dysfunction, ED) are generally recognized as common side effects after prostatectomy.
Among patients treated at centers performing large numbers of prostate cancer operations, urinary incontinence after prostatectomy, is usually temporary and resolves in most cases. Typical recovery of urinary control occurs over a period of weeks to several months after prostate removal if a nerve-sparing procedure is performed. In the absence of nerve-sparing, recovery of urinary control can take twice as long4. Apart from the use of nerve-sparing technique, the other principal factor found to affect urinary recovery after prostatectomy is patient age. A recent nationwide study found that about 5% to 10% of men in their 60’s reported long-term urinary leakage after prostatectomy whereas 15% of men in their 70’s had problematic urinary leakage5. Treatments available for men who experience durable urinary leakage include collagen injection (useful only in cases of mild leakage) or implantation of artificial urinary valves (artificial urinary sphincter). Urinary leakage is sufficiently severe to require such treatment in less than 3% of cases.
Impotence (or Erectile Dysfunction, ED) is the other principal issue that commonly affects quality of life after prostatectomy. Most men experience ED early after prostatectomy. Erections are typically poor in the first few months after prostatectomy and recover variably thereafter, depending on factors such as baseline sexual function, patient age, and use of nerve-sparing surgical technique. Even after nerve-sparing surgery, however, erection recovery can take months to years. Erections can be improved with medications such as Viagra, MUSE (a urethral suppository), caverject (injectible prostaglandin), or vacuum pump devices6. Although most men in their late 60’s or older do not recover quality erections comparable to their pre-treatment baseline, many are able to either adapt their sexual activity or use medications to maintain an adequate level of sexual functioning. On the other hand, the sexual recovery outlook for younger men who undergo a nerve-sparing procedure is more favorable than for older men: we and others have found that many men in their 40’s and 50’s can recover erections suitable for intercourse if they undergo nerve-sparing surgery as described by Walsh. However, only select centers with high volume surgical expertise have shown such favorable sexual recovery among their patients after nerve-sparing prostatectomy.
A recent study by our group (Figure 1) showed that bothersome, long-term urinary incontinence was relatively uncommon after radical prostatectomy compared to age-matched control men without prostate cancer7. In contrast, erectile dysfunction was more common. Bowel concerns did not affect prostatectomy patients, though such problems were occasionally encountered after radiation or brachytherapy, as described below.

Quality-of-Life after Radiation -External Beam Radiation Therapy

External beam radiotherapy to the pelvis is well established as a definitive therapeutic option for early stage prostate cancer. In the last decade, 3-Dimensional (3-D) conformal radiotherapy has emerged as a significant advance in external radiotherapy technique with improved cancer-free survival and reduced side effects over conventional radiotherapy. Although using the 3-D conformal technique reduces side effects from external radiation, these patients can nevertheless experience bothersome urinary, bowel, or sexual symptoms8. Unlike surgical patients in whom the urinary symptom of concern is incontinence or leakage, however, the urinary symptoms among radiation patients are characterized by burning or pain with urination (‘dysuria’), urinary frequency, urgency, obstruction, and (less commonly) bleeding. These are called urinary ‘irritative’ and ‘obstructive’ symptoms or problems. Unfortunately, these symptoms have largely been ignored in prior patient-report QOL studies. One recent study showed that these urinary irritative and obstructive symptoms were worse after radiation compared to surgery, and were even more profound after brachytherapy (radioactive seed implants; see below).6
External radiation can also affect erections and sexuality. Mantz et al., noted initially high potency rates immediately after conformal external radiation, followed by a gradual decline thereafter over 5 years, at which point half of men reported impotence (ED)9. Viagra, MUSE, caverject, and vacuum pumps can be helpful for maintaining an active sex life despite problems with erections after external radiation.
In a small proportion of patients, external radiation can lead to problematic bowel symptoms such as painful, frequent, or bloody bowel movements or fecal soiling10-12. Such bowel symptoms can be problematic for 5-15% of patients long-term after external radiation administered by the 3-D conformal technique; these rectal problems are less frequent than was previously seen after conventional radiation (Figure 1)7,13.

Figure 1

Severity of overall quality of life functions (urinary, bowel, and sexual bother)
reported by patients after localized prostate cancer therapy.
 
 

Reproduced with Permission see reference 7.

*The distribution of participant responses to each of three specific survey questions, representing the three highest loading EPIC bother items, are shown.
 

Quality-of-Life after Radiation Seed Implant - Interstitial Brachytherapy

There has been a rise in the use of interstitial brachytherapy (prostatic implantation of radioactive seeds) as primary treatment for localized prostate cancer in the past 5 years. Recent advances in radiographic imaging and implantation techniques have greatly improved the procedure, but because the technique is still evolving, QOL determinations after brachytherapy have been limited to only a few current studies. The principal advantage of brachytherapy over external radiation or prostatectomy is convenience of the treatment itself: brachytherapy can typically be completed in two or three outpatient visits sometimes including a brief overnight stay.
However, men receiving brachytherapy can commonly experience irritative urinary symptoms such as urinary burning, pain, frequency, or obstruction14,15. Urinary incontinence or leakage is also sometimes encountered after seed implants; up to 13% of patients treated at a leading brachytherapy/seed implant center reported leakage of more than a few drops, and 18% wore a pad for protection2. We found that long-term urinary irritative and obstructive symptoms were more severe after brachytherapy than after surgery or external radiation7. The combined possibility of either urinary leakage (in nearly 10% of men) or urinary irritation (burning, urgency, frequency or obstruction) may explain why patients undergoing brachytherapy reported more overall urinary problems than surgery or external radiation patients (Figure 1).
Early studies evaluating the effects of brachytherapy on erections and sexuality suggested that seed implants may have only limited effects on erections 6 months after treatment16. However, with longer follow-up, it has become clear that long-term effects on erections and sexuality 2 years after radioactive seed implants are not better than those observed with external radiation. As with external radiation, the full effect of seed implants on erections and sexuality develops gradually after treatment and can become substantial one or two years later17. Older patients and those who receive hormonal therapy before seed implantation were especially prone to problems with erections and sexuality.
The effect of brachytherapy on bowel function has also been examined18. More than one in ten patients treated at a national referral center for seed implants, reported rectal bleeding, diarrhea, or other rectal problems. A similar rate of rectal problems was confirmed in our study also (Figure 1)7. Brachytherapy or radioactive seed implants do not eliminate the possibility of side effects on urinary, bowel, or sexual QOL that had initially been observed after surgery or external radiation.

Quality-of-Life and Hormonal Therapy

Recent clinical trials have established a role for hormonal therapy as an effective adjuvant to either external radiation or surgery in higher risk prostate cancer patients19,20. Hormone therapy can be associated with problematic side effects unique to hormonal therapy (such as hot flashes, and gynecomastia) in nearly 20% of cases20. Other symptoms described as occurring during hormonal therapy for prostate cancer include loss of vitality or energy, weight gain, and fatigue. Possibly most common and surprisingly overlooked are the effects of hormonal therapy on erections: impotence during hormonal therapy is commonplace, and recovery of erections after stopping hormonal therapy is variable.
A recent study evaluated prostate cancer patients who were treated with hormone therapy with no surgery or radiation10. Impotence was reported by 80% of the men receiving. These findings underscore the need to inform patients about the specific side effects of hormone therapy before beginning such treatment.

Quality of Life and Watchful Waiting

There are different types of prostate cancer (as reflected by the grade or Gleason score that describes the microscopic appearance of prostate cancer) and some may not require aggressive treatment or intervention when they are first diagnosed. These include either very low Gleason score cancers or even some moderate grade cancers, depending on the age of the patient, the amount of cancer found on biopsy, and the patient’s general health status21,22. For this reason, observation, or watchful waiting, is a management alternative for some healthy men with low-risk, localized-early prostate cancer, or for men with other, serious health problems that may supercede the risk of an early stage prostate cancer. Similarly, aversion to possible side effects of therapy may influence patients to choose watchful waiting for their low-risk prostate cancers.
However, as no acute intervention is undertaken, watchful waiting can also have effects on QOL. These effects may range from psychological distress to overt symptoms related to the cancer itself. One study by Jonler et al. looked at patients who had elected watchful waiting for their localized prostate cancer23. One in five of these men (21%) reported some urinary problems and nearly one-third complained of some amount of time being spent worrying about the disease or the effects of treatment as well as some bother from their cancer. Interestingly, 96% of these men said they would choose watching waiting again.

Summary

Quality of life is an important consideration for patients when choosing treatment for prostate cancer as any treatment can affect the patient’s quality of life. The most common side effect of all prostate cancer treatments is problems with erections or sexuality, but many men maintain or recover a satisfactory ability to have erections, and can have a fulfilling sex life even after prostate cancer treatment. Urinary incontinence is common early after prostatectomy, but urinary control usually recovers in the first few months: In younger men who undergo surgery at referral centers, long-term, problematic urinary incontinence is uncommon. On the other hand, men treated by either interstitial brachytherapy or external-beam radiation can occasionally develop bothersome urinary symptoms such as burning, pain, frequency and urgency that can be equally as problematic as incontinence but have been largely ignored by researchers and physicians until recently. Even patients who elect watchful waiting are at risk for urinary obstruction that may later require treatment for the symptom. Rectal symptoms such as painful, frequent, bloody, or loose bowel movements can occur after external radiation or seed implants (brachytherapy), whereas such problems are rare after prostatectomy.
Despite possible treatment-related side-effects, most prostate cancer patients are very satisfied with their quality of life after prostate cancer therapy, and in most cases, the initial treatment eliminates the cancer effectively. With regard to long-term side effects of therapy, no treatment shows any clear advantage in overall quality of life over other therapies in localized prostate cancer, though each treatment has a different profile of types of side effects. To ease decisions regarding choice of therapy, further research is needed to better predict how individual patients will be affected by the various available prostate cancer treatments.

Nikhil L. Shah, DO
Postdoctoral Research Fellow
Department of Urology
University of Michigan
Ann Arbor, MI 48109-0944
shah@umich.edu

Martin G. Sanda, MD
Associate Professor
Director, Urology Research
Department of Urology
University of Michigan
Ann Arbor, MI, 48109-0944
msanda@umich.edu

 

---

Click over the logo below to visit the CancerNews site

---

Footnotes and References

---

1) An important component of evaluating quality of life effects of prostate cancer treatment rests with the methods used to measure morbidity. Traditionally, treatment-related morbidity was measured by relying on physicians, nurses, or other health-care practitioners to interpret symptom severity based on direct interaction between patients and the health-care practitioner. Large studies, however, have shown that such ‘physician-report’ methodology can underestimate the full range and severity of symptoms and the impairment on a patient’s quality of life2,3. To better measure outcomes after cancer therapy, Health-related quality of life (HRQOL) questionnaires that are primarily patient-driven were developed3. Given the importance of patient-focused HRQOL, ongoing studies will allow physicians to compare outcomes following various treatments for prostate cancer and assist patients in choosing the most appropriate therapy.

2) Talcott JA, Rieker P, Clark JA, et al: Patient-reported symptoms after primary therapy for early prostate cancer: Results of a prospective cohort study. J Clin Oncol 16:275-283, 1998.

3) Litwin MS, Hays RD, Fink A, Ganz PA, Leake B, Brook RH. The UCLA Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure. Medical Care 1998; 36(7):1002-1012.

4) Wei JT, Dunn RL, Marcovich R, et al. Prospective assessment of patient reported urinary continence after radical prostatectomy. J Urol, 2000;164(3 pt 1):744-748.

5) Stanford JL, Ziding F, Hamilton AS, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer. JAMA, 2000;283:354-360.

6) Pienta KJ, Sandler H, Shah NL, Sanda MG. “Prostate Cancer, Chapter 17.” In Cancer Mangement: A Multidisciplinary Approach, Sixth Edition. PRR Inc, Melville NJ (in press 2002).

7) Wei JT, Dunn RL, Sandler HM, McLaughlin PW, Montie JE, Litwin MS, Nyquist L, Sanda MG. Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer. J Clin Oncol, 2002 Jan 15;20(2):557-66.

8) Beard CJ, Propert KJ, Rieker PP, et al: Complicaitons after treatment with external-beam irradiation in early-stage prostate cancer patients: A prospective multi-institutional outcomes study. J Clin Oncol 15: 2230229, 1997.

9) Mantz CA, Nautiyal J, Awan A, Kopnick M, Ray P, et al. Potency preservation following conformal radiotherapy for localized prostate cancer: impact of neoadjuvant androgen blockade, treatment technique, and patient-related factors.Cancer J Sci Am. 1999 Jul-Aug;5(4):230-6.
 

10) Potosky AL, Legler J, Albertsen PC, Stanford JL, Gilliland FD, Hamilton AS, et al. Health outcomes after radical prostatectomy or radiotherapy for clinically localized prostate cancer: Results from the Prostate Cancer Outcomes Study (PCOS). J Natl Cancer Inst, 2000;92:1582-1592.

11) Madalinska JB, Essink-Bot ML, de Koning HJ, et al. Health-related quality of life effects of radical prostatectomy and primary radiotherapy for screen-detected or clinically diagnosed localized prostate cancer. J Clin Onc 19(6): 1619-1628, 2001.

12) Zelefsky, M.J., Wallner, K.E., Ling, C.C. et al: Comparison of the 5 year outcome and morbidity of three dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer. J Clin Oncol, 17: 517, 1999.

13) Zagars GK, Pollack K, von Eschenbach AC. Addition of radiation therapy to androgen ablation improves outcome for subclinically node-positive prostate cancer. Urology. 2001 Aug;58(2):233-9.

14) Krupski T, Petroni GR, Bissonette EA, et al. Quality-of-life comparison of radical prostatectomy and interstitial brachytherapy in the treatment of clinically localized prostate cancer. Urology 55(5): 736-42, 2000. (Theodoresco).

15) Brandeis JM, Litwin MS, Burnison CM, Reiter RE. Quality of life outcomes after brachytherapy for early stage prostate cancer. J Urol 2000; 163(3):851-7.

16) Arterbery VE, Frazier A, Dalmia P, et al. Quality of Life After Permanent Prostate Implant. Semin Surg Oncol 1997;13(6):461-466.

17) Hollenbeck BK, Dunn RL, Wei JT. Neoadjuvant Hormonal Therapy and Older Age Are Associated with Adverse Sexual Health-Related Quality-of-Life After Prostate Brachytherapy. Urology 2002;59:480-484.

18) Talcott JA, Clark JA, Stark PC, Mitchell SP. Long-Term Treatment Related Complications of Brachytherapy for Early Prostate Cancer: A Survey of Patients Previously Treated. J Urol 2001;166:494-499.

19) Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, Collette L, Pierart M. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin [see comments]. NEJM 1997; 337(5):295-300.

20) Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer [see comments]. NEJM 1999; 341(24):1781-8.

21) Albertsen PC, Hanley JA, Gleason DF, et al.: Competing Risk Analysis of Men Aged 55 to 74 Years at Diagnosis Managed Conservatively for Clinically Localized Prostate Cancer. JAMA 1998;280:975-980.

22) Epstein JL, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994 Feb 2;271(5):368-74.

23) Jonler, M, Nielson OS, Wolf H. Urinary symptoms, potency, and quality of life in patients with localized prostate cancer followed up with deferred treatment. Urology. 1998 Dec;52(6):1055-62; discussion 1063.