Campbell-Walsh Urology, 11th Edition

PART XIV

Prostate

117

Focal Therapy for Prostate Cancer

David C. Miller; Louis L. Pisters; Arie S. Belldegrun

Questions

1. Technical innovations improving cryotherapy for prostate cancer include all EXCEPT the use of:
2. transrectal ultrasound.
3. urethral warming catheters.
4. warming of neurovascular bundles.
5. thermocouples placed in critical areas of the prostate.
6. smaller-diameter cryoprobes allowing percutaneous insertion.
7. What is the most clinically important parameter of tissue ablation other than lowest temperature achieved by cryotherapy?
8. The diameter of the cryoprobe
9. The number of freeze/thaw cycles
10. The velocity of tissue thawing
11. The velocity of tissue freezing
12. The duration of freezing
13. What is the characteristic appearance of frozen tissue on ultrasound?
14. Mixed echogenicity
15. Hyperechogenicity
16. Anechogenicity
17. Hypoechogenicity
18. None of the above
19. Prostate cell death is likely to occur completely in a single freeze cycle when tissue temperature reaches:
20. 20° C.
21. 0° C.
22. − 20° C.
23. − 40° C.
24. none of the above.
25. Failure after prostate cryotherapy may be defined as:
26. failure to reach prostate-specific antigen (PSA) nadir by 2 months.
27. PSA cutoff greater than 0.1 ng/mL.
28. three consecutive elevations in PSA after nadir.
29. PSA rise of 2 ng/mL above post-treatment nadir.
30. c and d.
31. Two years after cryosurgery for clinical stage T2a, PSA 7, Gleason grade 3 + 4 cancer, a patient is found to have benign glands on a prostate biopsy specimen from the right apex. No malignancy is detected. The PSA level is detectable at 0.2 ng/mL. What is the next step in management?
32. Repeat cryoablation of the left lobe
33. Radiation therapy
34. Surveillance
35. Androgen deprivation
36. Repeat biopsy
37. Which clinical parameter most accurately predicts cancer control after cryotherapy?
38. PSA nadir less than 0.1 ng/mL
39. Preoperative Gleason score less than 6
40. Preoperative serum PSA level less than 15 ng/mL
41. A prostate volume less than 40 mL
42. Preoperative T stage
43. Potential advantages of primary cryotherapy for prostate cancer versus other local therapies include all EXCEPT:
44. it is capable of destroying a biologically heterogeneous population of cancer cells, including cell populations that are resistant to radiation therapy and hormonal therapy.
45. the freezing process can extend beyond the capsule of the prostate, potentially eradicating extracapsular disease.
46. it is proven to be beneficial with adjuvant therapies.
47. it can be repeated with minimal morbidity.
48. it can treat high Gleason-score prostate cancer.
49. Salvage cryotherapy for radiorecurrent prostate cancer:
50. will not reduce the PSA below 0.4 ng/mL.
51. may be useful in the control of local spread in the face of distant metastases.
52. has the same incidence of incontinence and fistula rates as primary cryotherapy.
53. may be performed on all patients for whom irradiation fails.
54. is unlikely to cure high-risk disease (PSA greater than 10 ng/nL and Gleason score greater than 7).
55. Clinical pretreatment factors associated with early treatment failure after salvage cryotherapy include:
56. postradiation PSA greater than 10 ng/mL.
57. recurrent cancer with Gleason score 9 or greater.
58. postradiation PSA doubling time 16 months or less.
59. all of the above.
60. none of the above.
61. Two months after cryotherapy, a patient complains of urinary frequency and dysuria. Urinalysis reveals pyuria. What is the most likely diagnosis?
62. Pelvic abscess
63. Urethral sloughing
64. Extravasation of urine
65. Rectourethral fistula
66. Bladder neck contracture
67. High-intensity focused ultrasound (HIFU) exerts what effect on prostate tissue?
68. Tissue fragmentation with disruption of vascular architecture
69. Coagulative necrosis
70. Nuclear injury
71. Cavitation
72. Disruption of protein synthesis
73. The most common side effect of HIFU for localized prostate cancer is:
74. impotence.
75. urinary retention.
76. bladder neck stricture.
77. urethrorectal fistulae.
78. incontinence.

Answers

1. c. Warming of neurovascular bundles.Use of transrectal ultrasonography (TRUS) for real-time monitoring of the freezing process, use of a urethral warming catheter, use of thermocouples placed in critical areas of the prostate, and improved cryoprobes allowing percutaneous insertion are technical innovations that have all contributed to improving cryotherapy for prostate cancer.
2. b. The number of freeze/thaw cycles.In a clinical setting, the number of freezing cycles, the lowest temperature achieved, and the existence of any regional "heat sinks" may be more important factors relating to cancer destruction. Repeating a freeze/thaw cycle results in more extensive tissue damage compared with a single cycle.
3. d. Hypoechogenicity.Frozen tissue is significantly different from unfrozen tissue in sound impedance, resulting in strong echo reflection at the interface of frozen and normal tissue. The frozen area can be seen as a well-marginated hyperechoic rim with acoustic shadowing by ultrasonography. Sonography provides no information about the temperature distribution within the ice, nor does it show the extent of freezing at the lateral or anterior aspects of the prostate.
4. d.− 40° C. Complete cell death is unlikely to occur at temperatures higher than − 20° C, and temperatures lower than − 40° C are required to completely destroy cells.
5. e. c and d.There is no established definition of biochemical failure after cryotherapy, and different PSA cutoff levels of 0.3, 0.4, 0.5, and 1.0 ng/mL have been used in numerous studies. The American Society for Therapeutic Radiology and Oncology (ASTRO) definitions of failure based on three consecutive rises in the PSA level or PSA nadir plus 2 (Phoenix definition) have also been used.
6. c. Surveillance.Benign epithelium, often very focal, has been seen in as many as 71% of patients after cryotherapy. The significance of benign epithelium is unknown, and such findings may represent areas of the prostate not frozen to low temperatures, perhaps in the area of the urethral warmer.
7. a. PSA nadir less than 0.1 ng/mL.Biochemical failure is lowest among patients who achieve a PSA nadir less than 0.1 ng/mL. Biopsy failure is also lowest in patients with PSA nadirs less than 0.1 ng/mL.
8. c. It is proven to be beneficial with adjuvant therapies.Potential advantages that primary cryotherapy for prostate cancer offers versus other local therapies include the capability of destroying a biologically heterogeneous population of cancer cells including cell populations that are resistant to radiation therapy and hormonal therapy, extension of the freezing process beyond the capsule of the prostate, potentially eradicating extracapsular disease, repeat of treatment with minimal morbidity, and treatment of high-Gleason-score prostate cancer.
9. e. Is unlikely to cure high-risk disease (PSA greater than 10 ng/mL and Gleason score greater than 7).In patients who have experienced radiation therapy failure for prostate cancer, those with a PSA greater than 10 ng/mL and Gleason score of the recurrent cancer greater than 7 are unlikely to be successfully salvaged. The incidence of incontinence and fistulas is higher in salvage cryotherapy.
10. d. All of the above.Clinical factors associated with early treatment failure after salvage cryotherapy for radiorecurrent prostate cancer include a PSA level greater than 10 ng/mL, Gleason score greater than or equal to 9, and a postradiation PSA doubling time of 16 months or less.
11. b. Urethral sloughing.Tissue sloughing is manifested by irritative and obstructive voiding symptoms. Pyuria is noted as well. Urinary retention is not uncommon. This condition typically occurs 3 to 8 weeks after the procedure. Initial management consists of antibiotics.
12. b. Coagulative necrosis.Highly focused sound energy results in mechanical and thermal effects on tissue. In the case of HIFU, the primary mechanism of tissue ablation is by raising the temperature in the tissue above the level needed to create coagulative necrosis.
13. b. Urinary retention.HIFU results in acute swelling of the prostate gland, resulting in temporary urinary retention that usually lasts 1 to 2 weeks. This occurs in the majority of patients with the other complications listed occurring much less frequently.

Chapter review

1. The feasibility of focal therapy for a multifocal disease such as prostate cancer is based on the presumption that an index lesion is primarily responsible for disease progression and metastases.
2. The index lesion as the focus of disease progression and/or metastases is supported by: (1) a volume of tumor must be equal to or greater than 0.5 mL to be significant, (2) some studies indicate that a single lesion drives metastases and progression, (3) the presence of Gleason 4 or 5 and volume predict disease progression, and (4) tumors solely composed of Gleason 6 disease rarely progress.
3. The use of TRUS-guided biopsy to guide focal therapy is fraught with the following difficulties: it overdiagnoses clinically insignificant cancer; misses clinically significant cancers in 30% of cases—usually in the anterior or apical regions; it may underrepresent true cancer burden; and repeat biopsies do not give consistent results.
4. Clinically significant prostate cancer is usually defined as a volume equal to or greater than 0.5 mL and/or a Gleason score of 3 + 4 or greater.
5. On initial biopsy there is no significant difference between a 12-core and a 20-core TRUS biopsy.
6. Color Doppler, ultrasound elastography, and multiparametric magnetic resonance imaging (MRI) with T2 weighting, dynamic contrast enhancement, diffusion weighting, and spectroscopy are improved imaging techniques to detect cancer, but still have significant limitations in accurately predicting or eliminating disease.
7. MRI-TRUS fusion targeted biopsy appears to detect both more significant and insignificant cancers when compared to TRUS biopsy.
8. HIFU and cryosurgery are the two modalities most often employed in focal therapy.
9. The mechanism of injury for cryotherapy involves dehydration of the cell with rupture of the cell membrane, toxic concentration of cellular constituents, and vascular injury.
10. Cell destruction is determined by the cooling rate, warming rate, and lowest temperature achieved.
11. Slow thawing is more effective in tissue destruction than rapid thawing.
12. A minimum temperature of − 40° C and a double freeze/thaw cycle with urethral warming is recommended for cryotherapy.
13. Complications of cryotherapy include erectile dysfunction, which is common; long-term incontinence in 1% to 10% of patients; symptomatic urethral sloughing in 5% to 15% of patients; pelvic, rectal, or perineal pain; rectal urethral fistula; and osteitis pubis in a minority of patients.
14. HIFU provides an energy source 10,000 times stronger than diagnostic ultrasound, producing a focal area of heat with temperatures that can exceed 80° C.
15. Complications following HIFU therapy include transient urinary retention in almost all, prolonged urinary retention in 9%, urethral stricture in 3.6%, and rectourethral fistula in 1%.
16. TURP is not indicated for patients receiving focal HIFU.
17. Photodynamic therapy (with aminolevulinic acid), focal thermal therapy, radiofrequency ablation, and focal irreversible electroporation have been used for focal therapy but have few published data to evaluate their effectiveness.
18. Complications for focal therapies are dependent on the energy source but generally include urinary retention, urethral stricture, urinary incontinence, urinary tract infection, erectile dysfunction, and rectourethral fistula.
19. There are few long-term data to evaluate the predictive characteristics of postfocal therapy: biopsies, imaging, and PSA dynamics.
20. Cryotherapy, HIFU, brachytherapy, and radical prostatectomy have been used for salvage therapy following failed radiation therapy, all of which have significant post-therapy complications. For example, following salvage radical prostatectomy, the average disease-free rate at 5 years is 30% to 50%, with a 50% incontinence rate, a 20% urethral stricture rate, close to 100% impotence rate, and a 1% to 3% rectal injury rate. Similarly, cryotherapy has an average incontinence rate of 50%, a rectourethral fistula rate of 0% to 3%, 80% impotence rate, and perineal pain rate of 20%. Significant long-term cancer-free survival data are not available for the most part for the nonradical prostatectomy therapies.