Evaluation of Outcomes Following Focal Ablative Therapy for Treatment of Localized Clinically Significant Prostate Cancer in Patients >70 Years: A Multi-institute, Multi-energy 15-Year Experience.

PURPOSE: In older patients who do not wish to undergo watchful waiting, focal therapy could be an alternative to the more morbid radical treatment. We evaluated the role of focal therapy in patients 70 years and older as an alternative management modality. MATERIALS AND METHODS: A total of 649 patients across 11 UK sites receiving focal high-intensity focused ultrasound or cryotherapy between June 2006 and July 2020 reported within the UK-based HEAT (HIFU Evaluation and Assessment of Treatment) and ICE (International Cryotherapy Evaluation) registries were evaluated. Primary outcome was failure-free survival, defined by need for more than 1 focal reablation, progression to radical treatment, development of metastases, need for systemic treatment, or prostate cancer-specific death. This was compared to the failure-free survival in patients undergoing radical treatment via a propensity score weighted analysis. RESULTS: Median age was 74 years (IQR: 72, 77) and median follow-up 24 months (IQR: 12, 41). Sixty percent had intermediate-risk disease and 35% high-risk disease. A total of 113 patients (17%) required further treatment. Sixteen had radical treatment and 44 required systemic treatment. Failure-free survival was 82% (95% CI: 76%-87%) at 5 years. Comparing patients who had radical therapy to those who had focal therapy, 5-year failure-free survival was 96% (95% CI: 93%-100%) and 82% (95% CI: 75%-91%) respectively (P < .001). Ninety-three percent of those in the radical treatment arm had received radiotherapy as their primary treatment with its associated use of androgen deprivation therapy, thereby leading to potential overestimation of treatment success in the radical treatment arm, especially given the similar metastases-free and overall survival rates seen. CONCLUSIONS: We propose focal therapy to be an effective management option for the older or comorbid patient who is unsuitable for or not willing to undergo radical treatment.

Prescription switching: Rationales and risks.

BACKGROUND: Therapeutic drug switching is commonplace across a broad range of indications and, within a drug class, is often facilitated by the availability of multiple drugs considered equivalent. Such treatment changes are often considered to improve outcomes via better efficacy or fewer side effects, or to be more cost-effective. Drug switching can be both appropriate and beneficial for several reasons; however, switching can also be associated with negative consequences. AIM: To consider the impact of switching in two situations: the use of statins as a well-studied example of within-class drug switching, and gonadotropin-releasing hormone (GnRH)-targeting drug switching as an example of cross-class switching. RESULTS: With the example of statins, within-class switching may be justified to reduce side effects, although the decision to switch is often also driven by the lower cost of generic formulations. With the example of GnRH agonists/antagonists, switching often occurs without the realisation that these drugs belong to different classes, with potential clinical implications. CONCLUSION: Lessons emerging from these examples will help inform healthcare practitioners who may be considering switching drug prescriptions.

Measuring testosterone and testosterone replacement therapy in men receiving androgen deprivation therapy for prostate cancer: A survey of UK uro-oncologists' opinions and practice.

AIM: To explore the practice and attitudes of uro-oncologists in the UK regarding monitoring testosterone levels and the use of testosterone replacement therapy (TRT) in their prostate cancer patients treated with androgen deprivation therapy (ADT). METHODS: An expert-devised online questionnaire was completed by the members of the British Uro-oncology Group (BUG). RESULTS: Of 160 uro-oncologists invited, 84 completed the questionnaire. Before initiating ADT in patients with non-metastatic prostate cancer, only 45% of respondents measured testosterone levels and 61% did not measure testosterone at all during ADT in the adjuvant or neoadjuvant setting. However, in men with metastatic prostate cancer, 71% of the uro-oncologists measured testosterone before starting ADT and the majority continued testing during treatment. Approximately two-thirds of respondents did not prescribe TRT for their patients who were in remission following neo(adjuvant) ADT and who had castration levels of testosterone. DISCUSSION: Among UK uro-oncologists, the measurement of testosterone levels before and during ADT was not typically part of routine practice in the management of patients with prostate cancer. However, testosterone levels were checked more frequently for patients with metastatic disease than disease at an earlier stage. Testing could be conducted in parallel with PSA measurement as testosterone levels are linked to biochemical failure. The majority of specialists participating in the survey did not prescribe TRT for their patients in remission following ADT. CONCLUSION: Uro-oncologists in the UK do not generally measure testosterone as part of their patient management and they remain cautious about the possible benefits of TRT in men with prostate cancer.

Organ-preserving surgery for penile cancer: description of techniques and surgical outcomes.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Organ-preserving surgeries for penile cancer have been described to reduce the morbidity associated with traditional operations. Patients derive better functional outcomes from penile-preserving surgery, although local recurrence rates can be higher. Excellent results can be obtained at large-volume centres. With close follow-up, local recurrences can be identified and treated promptly (often with further local excision). OBJECTIVE: • To describe the outcomes of organ-preserving surgery for penile cancer at a UK tertiary referral centre. PATIENTS AND METHODS: • Patients at Sunderland Hospital (UK) between 2001 and 2008 who had squamous cell tumours limited to the glans penis underwent penile-preserving surgery including total glansectomy and glanuloplasty, partial glansectomy, glans relining and distal penectomy with glans reconstruction. • Recurrence rates, cosmetic and functional outcomes were recorded. RESULTS: • In all, 65 patients were identified with a median follow-up of 40 months. Local recurrence was present in four patients (6%) despite 72% having intermediate or poorly differentiated tumours and 30% with T2 disease. • Complications included partial graft loss (1.5%), graft contractures (4.5%) and meatal stenosis (7.5%). • In all, 5% were deemed to have poor cosmetic outcome and 85% described good erections at 1 year after surgery. CONCLUSION: • Penile-preserving surgery can achieve good penile cancer control with minimal morbidity and reduced psychosexual side-effects.

Assessment of Return to Baseline Urinary and Sexual Function Following Primary Focal Cryotherapy for Nonmetastatic Prostate Cancer.

BACKGROUND: The oncological outcomes in men with clinically significant prostate cancer following focal cryotherapy are promising, although functional outcomes are under-reported. OBJECTIVE: To determine the impact of focal cryotherapy on urinary and sexual function, specifically assessing return to baseline function. DESIGN, SETTING, AND PARTICIPANTS: Between October 2013 and November 2016, 58 of 122 men who underwent focal cryotherapy for predominantly anterior clinically significant localised prostate cancer within a prospective registry returned patient-reported outcome measure questionnaires, which included International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-15) questionnaires. INTERVENTION: Standard cryotherapy procedure using either the SeedNet or the Visual-ICE cryotherapy system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was return to baseline function of IPSS score and IIEF erectile function (EF) subdomain. Cumulative incidence and Cox-regression analyses were performed. RESULTS AND LIMITATIONS: Probability of returning to baseline IPSS function was 78% at 12 mo and 87% at both 18 and 24 mo, with recovery seen up to 18 mo. For IIEF (EF domain), the probability of returning to baseline function was 85% at 12 mo and 89% at both 18 and 24 mo, with recovery seen up to 18 mo. Only the preoperative IIEF-EF score was associated with a poor outcome (hazard ratio 0.96, 95% confidence interval 0.93-0.999, p = 0.04). The main limitation was that only half of the patients returned their questionnaires. CONCLUSIONS: In men undergoing primary focal cryotherapy, there is a high degree of preservation of urinary and erectile function with return to baseline function occurring from 3 mo and continuing up to 18 mo after focal cryotherapy. PATIENT SUMMARY: In men who underwent focal cryotherapy for prostate cancer, approximately nine in 10 returned to their baseline urinary and sexual function. Keeping in mind that level 1 evidence and long-term data are still needed, in men who wish to preserve urinary and sexual function, focal cryotherapy may be considered an alternative treatment option to radical therapy.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason

Prospective evaluation of sexual function in patients receiving cryosurgery as a primary radical treatment for localized prostate cancer.

OBJECTIVE: To evaluate prospectively the sexual function of patients undergoing cryosurgery as a primary radical treatment for localized prostate cancer, as the development of 17 G cryotherapy probes has improved the delivery of this treatment, but one of the side-effects of cryosurgery is the development of erectile dysfunction (ED). PATIENTS AND METHODS: Between July 2003 and May 2008, 53 patients were treated using an argon-based third-generation cryotherapy system (Oncura, Arlington Heights, IL, USA). Prospective data were collected at 6 weeks, 3 months, then 3-monthly up to 1 year and subsequently 6-monthly. Patients were followed up for up to 54 months, with a median (mean) follow-up 36 (30.5) months. RESULTS: All 53 patients were followed after receiving cryosurgery as primary treatment for prostate cancer; 51 (96.3%) had ED at 6 weeks while two (3.7%) were experiencing partial erections. By 9 months one (2.4%) of 42 patients was fully potent using phosphodiesterase type-5 inhibitors, and six (14.3%) were experiencing partial erections. By 18 months eight (21%) of 39 patients followed up had regained full potency and by 24 months eight (24%) of 33 patients were fully potent and three (9%) experienced partial erections. CONCLUSION: While ED is a significant side-effect of cryotherapy, a considerable proportion of patients who have no ED before treatment (39%) recover full sexual function afterward. Focal nerve-sparing cryosurgery might be the way forward in an attempt to preserve erectile function in men who had no ED before treatment. Erectile aids should be made available for those patients for whom sexual dysfunction compromises the quality of their life and relationships.

Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry.

BACKGROUND: Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. OBJECTIVE: Early-medium-term cancer control and functional outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8mo [interquartile range (IQR) 19.5-36.7]. A total of 35 patients (28.7%) had National Comprehensive Cancer Network (NCCN) high risk and 87 (71.3%) had intermediate risk disease. Risk and zonal stratification included multiparametric magnetic resonance imaging (mpMRI) with targeted and systematic biopsies, or transperineal mapping biopsies. INTERVENTION: Focal cryoablation of MR-visible tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up involved prostate-specific antigen (PSA) monitoring, mpMRI, and for-cause biopsies. Primary outcome was failure-free survival (FFS), defined as transition to radical, whole-gland, or systemic therapy, or metastases/death. Secondary outcomes included adverse events and functional outcomes. RESULTS AND LIMITATIONS: A total of 80 (65.6%) had anterior ablation, 23 (19.7%) combined posterior and anterior ablation, and two (1.6%) posterior ablation alone (SeedNet or Visual-ICE, BTG plc). Median age was 68.7yr (IQR 64.9-73.8) and preoperative PSA 10.8ng/ml (IQR 7.8-15.6). Overall FFS at 3yr was 90.5% [95% confidence interval (CI) 84.2-97.3]. When stratified for the NCCN risk group, 3-yr outcomes were 84.7% (95% CI 71.4-100) in high risk and 93.3% (95% CI 86.8-100) in intermediate risk. At last follow-up, incontinence defined as any pad use was 0/69 (0%) and erectile dysfunction (defined as erections insufficient for penetration) was 5/31 (16.1%). Limitations include lack of long-term outcomes. CONCLUSIONS: Focal cryotherapy primarily for anterior intermediate and high-risk prostate cancer results in good rates of cancer control and low rates of treatment-related side effects. PATIENT SUMMARY: In this multicentre study of 122 patients undergoing focal cryotherapy for medium- to high-risk prostate cancer, at 3yr, no patient died from their cancer whilst failure-free survival, was approximately 90%. None of the patients needed pads for managing urine leakage, although 16% had erection problems.

Oncologic Outcomes of Penile Cancer Treatment at a UK Supraregional Center.

OBJECTIVE: To report contemporary treatment outcomes of penile squamous cell carcinoma at a UK supraregional center, including patterns of therapy, oncologic results, and long-term survival. PATIENTS AND METHODS: Patients with squamous cell carcinoma treated during the period January 2000 to January 2011 were included. Records were reviewed to identify the mode of therapy (penile preserving or amputative surgery), pathology reports (reclassified according to the 2009 tumor-nodes-metastasis classification), recurrence patterns, and cancer-specific survival (CSS). Kaplan-Meier plots were used for survival analyses. RESULTS: Two hundred three patients were identified with a median follow-up of 61 months. At presentation, 165 patients (82%) were node negative, 31 (15%) were node positive, and 7 (3%) had metastatic disease. Management was penile preserving surgery (n = 99, 49%), partial penectomy (n = 49, 24%), radical penectomy (n = 48, 24%), and chemotherapy or radiotherapy for metastatic disease (n = 7, 3%). After organ-preserving surgery, the local recurrence rate was 18% (compared with 4% for amputative surgery), with 94% of recurrences occurring within 3 years. Histopathologic staging was as follows, with pTis (20%), pT1 (27%), pT2 (27%), pT3 (7%), and pT4 (1%). Kaplan-Meier analysis showed a 5-year CSS of 85% and a 10-year CSS of 81%. Five-year CSS was noted to decrease with advancing stage with pN0 tumors (92%), N1 (73%), N2 (61%), N3 (33%), and M1 (0%; P <.0001). CONCLUSION: Supraregional penile cancer management has led to considerable clinical experience in our center over the past decade. Close follow-up is vital to pick up local recurrence after penile-preserving surgery. Overall oncologic outcomes are good with a 5-year CSS of 85%.

Salvage treatment in prostate cancer: a clinical approach.

Radiotherapy is the main salvage option after primary radical prostatectomy. Radical prostatectomy, cryosurgical ablation and high-intensity focused ultrasound are the main salvage options after primary radiotherapy. After primary radiotherapy, long-term oncological outcome of salvage radical prostatectomy and salvage cryosurgical ablation is fairly comparable with the results of primary radical prostatectomy and primary cryosurgical ablation. Side effects of salvage radical prostatectomy in elite centers are acceptable and side effects of salvage cryosurgical ablation in tertiary centers are almost the same as after primary cryosurgical ablation. Good long-term data after salvage high-intensity focused ultrasound are lacking and the risk of side effects is considerable. After primary radical prostatectomy, there is a high level of evidence for oncological benefit of salvage radiotherapy. Careful patient selection is important for all salvage modalities.

The prognostic value of transrectal ultrasound guided biopsy in patients over 70 years old with a prostate specific Antigen (PSA) level ≤ 15 ng/ml and normal digital rectal examination: a 10-year prospective follow-up study of 427 consecutive patients.

INTRODUCTION: As a urologist, it is common to review a patient above the age of 70 being referred to a prostate assessments clinic with an elevated PSA. We evaluate the prognosis of these patients clinically as there is no international consensus on the exact PSA cutoff level or a single international guideline as to when these patients should be offered a prostate biopsy. PATIENTS AND METHODS: On receiving ethic committee approval, we recruited 427 consecutive patients aged 70 years and above referred with a PSA of ≥ 4 ng/ml, from January 1996 to December 2000, into our study. All patients were assessed, examined with a digital rectal examination (DRE) of the prostate, and a subsequent prostate biopsy. We followed up on their histologic diagnosis for up to 10 years and analyzed their outcome. The main outcome measures were disease-free survival and overall survival, stratified according to the PSA level (≤ 15 vs. >15 ng/ml) and DRE findings (normal vs. sbnormal). RESULTS: There was a statistically significant difference in the overall survival (P value < 0.011) and disease specific survival (P value < 0.0001) of cancer patients with a PSA was >15 ng/ml and an abnormal DRE. However, in patients with a PSA ≤ 15 ng/ml and normal DRE, the incidence of cancer was low and they had no disease-specific or overall survival benefit. CONCLUSIONS: A policy of deferring prostate biopsy in patients with a PSA ≤ 15 ng/ml and normal DRE (Group A) would significantly decrease the need of unnecessary prostate biopsies. Within this group, patients did not have any survival advantage compared with those without cancer. We conclude that up to 20% of the prostate biopsies performed in this age group could have been avoided.

Salvage cryotherapy: is there a role for focal therapy?

Prostate cancer treatment has undergone vast development over the last few decades, but the most notable changes have included nerve-sparing open radical prostatectomy, laparoscopic radical prostatectomy, including robot-assisted and, more recently, cryotherapy and high-intensity focused ultrasound (HIFU). While radical surgery is the current gold standard, the less invasive therapeutic options of cryotherapy and HIFU are regarded as largely experimental by governing bodies. In the case of cryotherapy, a wealth of experience has been accumulated demonstrating its efficacy. Initially used as a salvage treatment for radiation-failed prostate cancer, cryotherapy has been widely used as a primary treatment for localized and locally advanced prostate cancer. More recently, there has been interest expressed in the concept of focal therapy in prostate cancer. This has been evaluated as a primary treatment for prostate cancer, but little information is available regarding the potential use as a salvage treatment. In this article, we evaluate the potential for focal treatment in the salvage setting.

Third-generation cryotherapy for prostate cancer in the UK: a prospective study of the early outcomes in primary and recurrent disease.

OBJECTIVE: To present the early results of the use of third-generation cryotherapy in primary and recurrent prostate cancer at one UK centre. PATIENTS AND METHODS: Over a 14-month period 51 patients underwent cryotherapy for prostate cancer. In 31 patients cryotherapy was used as the primary treatment and in 20 as a salvage treatment after radiotherapy or hormone ablation. Data were collected prospectively and the median follow-up was 9 months. RESULTS: The prostate-specific antigen (PSA) level decreased to <0.5 ng/mL in 79% of patients undergoing primary treatment and in 67% of patients undergoing salvage treatment. A higher Gleason grade and PSA levels were associated with a poorer outcome. No patient developed a fistula, 4% developed urinary retention requiring transurethral prostatectomy and 4% had persistent incontinence. The rates of erectile dysfunction were high (86%). The median inpatient stay was 2 days. CONCLUSION: Early results suggest that cryotherapy offers a safe alternative for primary and recurrent prostate cancer, particularly for older and less fit patients. Long-term data are required to assess the durability of response and the effect on survival.

Urethral catheter induced pseudoaneurysm of the bulbar artery.

Injuries of the urethra due to urethral catheter have been well recognised. We report a case of pseudoaneurysm of the artery to the bulb of the penis which formed due to necrosis of the arterial wall secondary to prolonged pressure due to a wrongly placed urethral catheter. The catheter was inflated in the bulbar urethra and left during surgery for 4 hours. The patient developed intermittent severe urethral bleeding. An angiogram of internal iliac artery showed a pseudo aneurysm involving the bulbar artery with arteriovenous communication. Super selective embolization of the feeding vessel was performed with cessation of the blood fl ow immediately. To our knowledge, pseudoaneurysm of the bulbar artery of penis has not previously been described.