Burden of illness for metastatic melanoma in Canada, 2011-2013.

BACKGROUND: Detailed epidemiology for patients with advanced metastatic melanoma in Canada is not well characterized. We conducted an analysis of patients with this disease in the province of Ontario, with the aim being to study the presentation, disease characteristics and course, and treatment patterns for malignant melanoma. METHODS: In this Canadian observational prospective and retrospective study of patients with malignant melanoma, we used data collected in the Canadian Melanoma Research Network (cmrn) Patient Registry. We identified patients who were seen at 1 of 3 cancer treatment centres between April 2011 and 30 April 2013. Patient data from 2011 and 2012 were collected retrospectively using chart records and existing registry data. Starting January 2013, data were collected prospectively. Variables investigated included age, sex, initial stage, histology, mutation type, time to recurrence, sites of metastases, resectability, and previous therapies. RESULTS: A cohort of 810 patients with melanoma was identified from the cmrn registry. Mean age was 58.7 years, and most patients were men (60% vs. 40%). Factors affecting survival included unresectable or metastatic melanoma, initial stage at diagnosis, presence of brain metastasis, and BRAF mutation status. The proportion of surviving patients decreased with higher initial disease stages. CONCLUSIONS: Using registry data, we were able to determine the detailed epidemiology of patients with melanoma in the Canadian province of Ontario, validating the comprehensive and detailed information that can be obtained from registry data.

Multidisciplinary management of locally advanced and metastatic cutaneous squamous cell carcinoma.

Non-melanoma skin cancers are the most prevalent form of cancer, with cutaneous squamous cell carcinoma (cscc) being the 2nd most common type. Patients presenting with high-risk lesions associated with locally advanced or metastatic cscc face high rates of recurrence and mortality. Accurate staging and risk stratification for patients can be challenging because no system is universally accepted, and no Canadian guidelines currently exist. Patients with advanced cscc are often deemed ineligible for either or both of curative surgery and radiation therapy (rt) and, until recently, were limited to off-label systemic cisplatin-fluorouracil or cetuximab therapy, which offers modest clinical benefits and potentially severe toxicity. A new systemic therapy, cemiplimab, has been approved for the treatment of locally advanced and metastatic cscc. In the present review, we provide recommendations for patient classification and staging based on current guidelines, direction for determining patient eligibility for surgery and rt, and an overview of the available systemic treatment options for advanced cscc and of the benefits of a multidisciplinary approach to patient management.

Real-world outcomes of nivolumab and cabozantinib in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Objectives: In the present study, we explored the real-world efficacy of the immuno-oncology checkpoint inhibitor nivolumab and the tyrosine kinase inhibitor cabozantinib in the second-line setting. Methods: Using the International Metastatic Renal Cell Carcinoma Database Consortium (imdc) dataset, a retrospective analysis of patients with metastatic renal cell carcinoma (mrcc) treated with nivolumab or cabozantinib in the second line after prior therapy targeted to the vascular endothelial growth factor receptor (vegfr) was performed. Baseline characteristics and imdc risk factors were collected. Overall survival (os) and time to treatment failure (ttf) were calculated using Kaplan-Meier curves. Overall response rates (orrs) were determined for each therapy. Multivariable Cox regression analysis was performed to determine survival differences between cabozantinib and nivolumab treatment. Results: The analysis included 225 patients treated with nivolumab and 53 treated with cabozantinib. No significant difference in median os was observed: 22.10 months [95% confidence interval (ci): 17.18 months to not reached] with nivolumab and 23.70 months (95% ci: 15.52 months to not reached) with cabozantinib (p = 0.61). The ttf was also similar at 6.90 months (95% ci: 4.60 months to 9.20 months) with nivolumab and 7.39 months (95% ci: 5.52 months to 12.85 months) with cabozantinib (p = 0.20). The adjusted hazard ratio (hr) for nivolumab compared with cabozantinib was 1.30 (95% ci: 0.73 to 2.3), p = 0.38. When adjusted by imdc criteria and age, the hr was 1.32 (95% ci: 0.74 to 2.38), p = 0.35. Conclusions: Real-world imdc data indicate comparable os and ttf for nivolumab and cabozantinib. Both agents are reasonable therapeutic options for patients progressing after initial first-line vegfr-targeted therapy.

Randomized phase II study of two doses of gefitinib in hormone-refractory prostate cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment. RESULTS: None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade 1 to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%; 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline. CONCLUSION: Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.

Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone.

PURPOSE: A combination of mitoxantrone plus prednisone is preferable to prednisone alone for reduction of pain in men with metastatic, hormone-resistant, prostate cancer. The purpose of this study was to assess the effects of these treatments on health-related quality of life (HQL). PATIENTS AND METHODS: Men with metastatic prostate cancer (n = 161) were randomized to receive either daily prednisone alone or mitoxantrone (every 3 weeks) plus prednisone. Those who received prednisone alone could have mitoxantrone added after 6 weeks if there was no improvement in pain. HQL was assessed before treatment initiation and then every 3 weeks using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (EORTC QLQ-C30) and the Quality of Life Module-Prostate 14 (QOLM-P14), a trial-specific module developed for this study. An intent-to-treat analysis was used to determine the mean duration of HQL improvement and differences in improvement duration between groups of patients. RESULTS: At 6 weeks, both groups showed improvement in several HQL domains, and only physical functioning and pain were better in the mitoxantrone-plus-prednisone group than in the prednisone-alone group. After 6 weeks, patients taking prednisone showed no improvement in HQL scores, whereas those taking mitoxantrone plus prednisone showed significant improvements in global quality of life (P =.009), four functioning domains, and nine symptoms (.001 < P <. 01), and the improvement (> 10 units on a scale of 0 to100) lasted longer than in the prednisone-alone group (.004 < P <.05). The addition of mitoxantrone to prednisone after failure of prednisone alone was associated with improvements in pain, pain impact, pain relief, insomnia, and global quality of life (.001 < P <.003). CONCLUSION: Treatment with mitoxantrone plus prednisone was associated with greater and longer-lasting improvement in several HQL domains and symptoms than treatment with prednisone alone.

Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (2',2'-difluorodeoxycytidine) in previously untreated patients with advanced transitional cell carcinoma. PATIENTS AND METHODS: Forty-one patients with measurable advanced transitional cell carcinoma who had received no prior chemotherapy for metastatic disease were scheduled to receive gemcitabine 1,200 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 of a 28-day cycle. Prior adjuvant or neoadjuvant therapy for locally advanced disease was allowed if this was completed greater than 1 year prior to study entry. All patients were treated on an outpatient basis. RESULTS: There were three complete responses and six partial responses seen in 37 assessable patients, for an overall response rate of nine of 37 (24.3%; 95% confidence interval, 12 to 41). Four patients remain in remission at 14, 23, 24, and 31 months. The median survival was 8 months with 17% of patients alive at 2 years. Treatment generally was well-tolerated with three patients having > or = grade 3 nonhematologic toxicity, five having grade 3 neutropenia, two having grade 3 thrombocytopenia, and two episodes of febrile neutropenia. Most patients were able to receive the drug as scheduled with the primary reason for dose reduction or dose delay being neutropenia. CONCLUSION: Gemcitabine has promising single-agent activity against urothelial cancer with a favorable toxicity profile. Further studies in combination with other active agents are warranted.

Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain.

PURPOSE: To compare the incidence of palliative response in patients with hormone-resistant prostate cancer (HRPC) treated with mitoxantrone and prednisone (MP) plus clodronate with that of patients treated with MP plus placebo. MATERIALS AND METHODS: Men with HRPC, bone metastases, and bone pain were randomly assigned to receive clodronate 1,500 mg administered intravenously (IV) or placebo every 3 weeks, in combination with mitoxantrone 12 mg/m2 IV every 3 weeks and prednisone 5 mg orally bid. Patients completed the present pain intensity (PPI) index and Prostate Cancer-Specific Quality-of-Life Instrument at each treatment visit and used a diary to record analgesic use on a daily basis. The primary end point was a reduction to zero or of two points in the PPI or a decrease of 50% in analgesic intake, without increase in either. RESULTS: The study accrued 209 eligible patients over 44 months. One hundred sixty patients (77%) had mild PPI scores (1 or 2), and 49 (24%) had moderate PPI scores (3 or 4). The primary end point of palliative response was achieved in 46 (46%) of 104 patients on the clodronate arm and in 41 (39%) of 105 patients on the placebo arm (P =.54). The median duration of response, symptomatic disease progression-free survival, overall survival, and overall quality of life were similar between the arms. Subgroup analysis suggested possible benefit in patients with more severe pain. CONCLUSION: MP provides useful palliation in symptomatic men with HRPC. Clodronate does not increase the rate of palliative response or overall quality of life. Clodronate may be beneficial to patients who have moderate pain, but this requires further confirmation.

Phase II study of troxacitabine (BCH-4556) in patients with advanced and/or metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: A multi-institution phase II study was undertaken by National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma. PATIENTS AND METHODS: Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks. RESULTS: Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically. CONCLUSION: Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this.

Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.

PURPOSE: To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. PATIENTS AND METHODS: We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. RESULTS: Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. CONCLUSION: Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Role of transrectal ultrasound guided salvage cryosurgery for recurrent prostate carcinoma after radiotherapy.

Despite improvements in treatment of localized prostate cancer, local recurrence remains a significant problem. A total of 46 patients with proven local cancer recurrence following external beam radiotherapy entered a prospective clinical trial using ultrasound-guided cryosurgery to ablate the residual prostate gland. Persistent complications included one urethra-rectal fistula, incontinence (2), retention (3), and treatment induced erectile dysfunction (7). Using the PSA definitions for biochemical failure as PSA>or=0.3 ng/ml, the Kaplan-Meier plots showed the incidence of patients to be free of biochemical recurrence at 51 and 44% at 1 and 2 y, respectively. For a PSA>or=1.0, the values at 1 and 2 y were 72 and 58%.

Treatment of skeletal disease in breast cancer with clodronate.

Complications of breast cancer involving the skeleton include hypercalcaemia, bone pain and fracture. These complications arise because of progressive osteolysis which is in turn dependent on the activation of osteoclasts by tumour and host tissues. Clodronate is a powerful inhibitor of osteoclastic bone resorption which led us to evaluate its potential in metastatic breast cancer. When given intravenously it lowers serum calcium in the majority of hypercalcaemic patients. A convenient regimen is 600 mg iv as a single dose infused over several hours. We have additionally shown in a double-blind cross-over study that this regimen also has a significant effect on bone pain. This had led us to assess the longer term effects of clodronate by mouth in a prospective double-blind study of patients with established skeletal metastases. These studies are not yet complete but the agent appears to prevent hypercalcaemia and trends are emerging which indicate that the incidence of bone pain and fractures may also decrease.

Phase II trial of pegylated-liposomal doxorubicin in the treatment of locally advanced unresectable or metastatic transitional cell carcinoma of the urothelial tract.

34 patients with advanced unresectable or metastatic urothelial carcinoma who had not received prior chemotherapy for metastatic disease were treated with pegylated-liposomal doxorubicin (PLD) 50 mg/m(2) by a 1-h intravenous infusion (i.v.) every 4 weeks in a multi-institutional phase II trial. 6 of 30 evaluable patients had a partial response to treatment (20%; 95% Confidence Interval (CI), 8-39%) and seven patients had stable disease. Toxicities were primarily non-haematological, but severe palmar-plantar erythrodysesthesia (PPE), lethargy and anorexia were infrequent. Despite a high proportion of patients with poor prognostic features, PLD had clinically significant activity in urothelial cancer in this study. The activity and unique toxicity profile of this drug make it of interest for further study in advanced urothelial cancers in combination with other active agents.

A double-blind, crossover trial of intravenous clodronate in metastatic bone pain.

After a baseline symptom and laboratory assessment, 24 patients with metastatic bone disease and pain were randomized to receive either a 4-hr intravenous infusion of 2-dichloromethylene bisphosphonate (Cl2MDP), 600 mg in 500 mL of normal saline, or a 4-hr placebo infusion, 500 mL of normal saline. The administration was double blind. After 1 wk, the assessment was repeated and the patients were crossed over to the alternate treatment. After 1 more wk, a final assessment and blinded choice by the patient and investigator took place. Of the 21 evaluable patients, 12 (57%) chose the Cl2MDP and 4 (19%) chose the placebo; 5 (24%) patients did not have a specific preference (p = NS). The investigator chose the Cl2MDP in 14 (67%) cases, placebo in 6 (29%) cases and was unable to discern a difference in 1 (5%) case (p less than 0.05). The patients and investigator made similar selections in 16 (76%) instances. On the visual analogue scale assessments, a significant decrease in pain scores was observed following the Cl2MDP infusion (p less than 0.01) and an increase in activity scores was also demonstrated (p less than 0.01). No significant difference in the daily oral morphine equivalent analgesic requirement was demonstrated for either arm. No difference in clinical and laboratory parameters of toxicity was evident between the placebo and Cl2MDP arms of the trial. Our preliminary findings suggest that Cl2MDP is safe, and has analgesic properties that may prove to be useful in the management of metastatic bone pain.

A randomized, controlled trial of intravenous clodronate in patients with metastatic bone disease and pain.

To evaluate the effectiveness of intravenous clodronate in ameliorating refractory bone pain in patients with metastatic bone disease, 60 patients with established osseous metastases and persistent bone pain were randomized to receive either clodronate (600 mg or 1500 mg in 500 mL of normal saline) or 500 mL of saline as placebo. After 2 weeks, the patients were crossed over to receive the alternate treatment. After another 2 weeks, each patient and investigator made a blinded choice. Daily visual analogue scales (VAS) and analgesic diaries were recorded throughout the study period. Forty-six patients were evaluable (77%). A treatment x period interaction was identified in the VAS and daily morphine equivalent dose (DMED) scores. First period analysis of the VAS scores for general pain, pain at rest, and pain upon movement demonstrated an average reduction of 13, 14, and 24 mm, respectively, from baseline, but were not significantly different from changes following placebo. The average change in DMED was -6.4 (SE = 2.9) following clodronate and was +24.6 (SE = 14.9) following placebo (p = 0.03). In the blinded choice of which agent resulted in improvement in pain, 26 (57%) patients chose clodronate, 12 (26%) chose placebo, and eight (17%) had no preference (p = 0.0021). For the investigators who also made a blinded selection, clodronate was chosen in 30 (65%) patients, placebo in ten (22%) patients, and no difference was apparent in six (13%) (p < 0.0001). Intravenous clodronate appeared to have analgesic effect in patients with refractory bone pain due to metastatic bone disease. The optimal dose and duration of effect require further evaluation, particularly in patients with stable disease and persistent bone pain.

Analysis of prognostic factors in men with metastatic prostate cancer. Uro-Oncology Group of Northern Alberta.

We determined the influence of the extent of disease on bone scan, serum testosterone, patient age, performance status, method of initial diagnosis, Gleason grade, clinical stage at diagnosis, serum acid phosphatase, serum prostate specific antigen (PSA) and primary hormonal treatment on survival. The clinical and hormonal data were obtained when the presence of metastatic disease was established and treatment was to be initiated in 162 men with metastatic prostate cancer. Mean followup was 16 months (range 1 to 105 months). A total of 70 men (43.2%) died of the metastatic disease during the evaluation period. Log rank analysis revealed that only serum testosterone (p = 0.035) and extent of disease on bone scan (p = 0.003) significantly affected over-all survival. A trend (p = 0.068) towards decreased survival was observed with increasing values of PSA. Increasing values of acid phosphatase positively correlated with extent of disease on bone scan but was not a significant independent prognostic factor. Patient age, performance status, clinical stage, method of initial diagnosis, Gleason grade and type of hormonal treatment did not significantly influence survival. Upon using multivariate Cox analysis, only extent of disease on bone scan was significantly correlated with over-all survival (p less than 0.014). PSA may also be influential but longer duration of followup will be necessary. We conclude that extent of disease on bone scan is the most important prognosticator of the analyzed factors and that serum testosterone may be of value.

A retrospective analysis of the relationship between changes in serum PSA, palliative response and survival following systemic treatment in a Canadian randomized trial for symptomatic hormone-refractory prostate cancer.

BACKGROUND: To investigate the relationship between changes in serum PSA, palliative response and survival following systemic treatment for symptomatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A retrospective review of 161 patients, treated with mitoxantrone and prednisone (M + P) (n = 80), or prednisone alone (P) (n = 81) from a Canadian randomized phase III clinical trial. PSA response was defined by > or =50% decline compared to baseline. Palliative response was defined by the primary and secondary endpoints of the trial. All responses were required to be maintained on two visits at least three weeks apart. The Cox proportional hazards model and a landmark analysis (at nine weeks) were used to evaluate survival differences between PSA responders and non-responders. RESULTS: Using an intent-to-treat analysis in which patients with missing PSA data are considered non-responders, 34% of M + P and 11% of P patients achieved a PSA response (P = 0.0001). Nineteen of thirty-six (53%) patients with PSA response and twenty-six of ninety (29%) patients without PSA response achieved a palliative response (P = 0.001 Chi-square test, phi coefficient = 0.28). From the landmark analysis. PSA responders had longer survival than non-responders (P = 0.009). In multivariate analysis, better performance status, higher hemoglobin and PSA response (P < 0.001) predicted for survival, but palliative response did not (P = 0.11). CONCLUSIONS: There is significant but imperfect statistical association between PSA response and palliative response. PSA response was associated with longer survival. Patients treated with M + P were more likely to achieve a PSA response and a palliative response than those treated with P.

Compliance of clinical stage I nonseminomatous germ cell tumor patients with surveillance.

PURPOSE: We evaluate compliance and its effect on the outcome of patients with clinical stage I nonseminomatous germ cell tumor who underwent post-orchiectomy surveillance at the Tom Baker Cancer Centre. MATERIALS AND METHODS: From 1980 to 1994, 76 evaluable patients underwent surveillance at the Tom Baker Cancer Centre. The surveillance protocol consisted of clinical evaluation, chest x-ray and serum tumor marker measurements monthly in year 1, every 2 months in year 2, every 6 months in years 3 to 5 and yearly in years 6 to 10. Abdomen and pelvic computerized tomography (CT) were scheduled every 2 months in year 1 and every 4 months in year 2. Noncompliance was defined as missing 2 or more consecutive clinic visits, tumor marker measurements or chest x-rays or 1 or more CT scans. RESULTS: Compliance with clinical evaluations was 61.5% in year 1 and 35.5% in year 2, whereas compliance with CT was only 25% and 11.8% in years 1 and 2, respectively. By univariate analysis diagnosis before 1990 predicted noncompliance, while age, marital status and distance from the center did not. Recurrent disease was detected in 28 patients (37%) at a median of 5.5 months after orchiectomy (range 1 to 49.5). Among the 47 compliant patients 23 had relapse and none died. Among the 29 noncompliant patients 5 had relapse and 2 died with central nervous system disease. CONCLUSIONS: Overall compliance with this surveillance program was poor but this study was too small to demonstrate whether poor compliance adversely affects overall survival.

Prospective trial of cryosurgical ablation of the prostate: five-year results.

OBJECTIVES: To determine in a prospective pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma. METHODS: A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998. All patients had histologically proved adenocarcinoma of the prostate, with prostate-specific antigen (PSA) readings of less than 30 ng/mL. Clinical evaluations, PSA determinations, and patient self-reported quality-of-life questionnaires (functional assessment of cancer treatment-prostate; FACT-P) were used to determine biochemical and clinical disease-free status and complications. Patients had a mean follow-up of 50 months (minimum 36). RESULTS: Follow-up biopsies were performed in 73 patients, and 72 were negative for malignancy after one or more treatments. Ten patients required two treatments and 1 patient required three treatments. The 5-year overall and cancer-specific survival rate was 89% (95% confidence interval, 83% to 97%) and 98.6% (95% confidence interval, 96% to 100%), respectively. The undetectable PSA rate (less than 0.3 ng/mL) for low-risk patients (n = 13) was 60% at 5 years; for moderate-risk patients (n = 23), it was 77%, and for high-risk patients (n = 40), 48%. The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75%, 89%, and 76%. Sloughing occurred in 3 patients (3.9%), incontinence in 1 (1.3%), and testicular abscess in 1 (1.3%). At 3 years, 18 (47%) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse, 5 spontaneously and 13 with sildenafil or prostaglandin. CONCLUSIONS: The results of this prospective evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer.