Dr. Kevin Slawin

Dr. Slawin has focused his research efforts on translational medicine throughout his career. One example is the discovery of BPH-A and -2proPSA, molecular forms of free PSA that are now on the cusp of FDA approval and that will allow better distinction of the causes of elevated PSA levels in patients. Studies published by Dr. Slawin and his research associates have identified and validated novel molecular markers of prostate cancer progression, and he has developed electronic nomograms that assist physicians in establishing the risk of prostate cancer progression for individual patients. (See www.prostatecenter.com and www.drslawin.com.) These are his current research programs:

Click on any topic for more detail.

Improving outcomes after robotic prostatectomy

Over the years, outcomes after prostate cancer treatment have steadily improved because of increasing physician skill and experience and the integration of new technologies such as robotic prostatectomy, nerve grafting, cryotherapy, and image-guided approaches to external beam radiotherapy. Numerous published studies have demonstrated that physician experience is a key determining factor in cancer cure rate, complication reduction, and recovery rate after open and minimally invasive approaches to prostate cancer surgery, like robotic prostatectomy.

Dr. Slawin has developed and maintained the secure, online, relational Caisis™ database, which contains all cancer and quality-of-life data available on every patient who has received treatment under his direction while he was the Director of The Baylor Prostate Center, and more recently, since he became Director of the Texas Prostate Center in the Vanguard Urologic Institute.

All patients complete a comprehensive, validated, quality-of-life questionnaire before treatment, which is shared with researchers at Memorial Sloane Kettering Cancer Center (MSKCC), and each patient provides additional information periodically after treatment, which is also stored in the Caisis database. Analysis of these data has led to numerous publications and presentations at national academic meetings reporting key insights on how to more effectively manage prostate cancer patients to maximize both cure rates and quality of life after treatment.

With the patient data in the Caisis system as the foundation for a thorough and systematic continuous “quality improvement” program, subtle changes in surgical techniques can be evaluated in an accurate and unbiased manner with respect to their effects on important outcomes. Researchers at the Vanguard Urologic Institute and Texas Prostate Center have been able to develop unique techniques for performing prostate cancer surgery, both open and robotic, that are tailored to individual patient circumstances and that have been proven to lead to the best achievable results.

The Caisis database platform has enabled Dr. Slawin to easily compare and combine data with other top academic institutions, like MSKCC, in order to perform multicenter studies for validation of observations from smaller, single-center studies. For example, in the prestigious Journal of the American Medical Association, Dr. Slawin was able to publish, as the supervising investigator, an important multicenter study demonstrating the effectiveness of salvage radiation therapy for patients with cancer recurrence after radical prostatectomy. These studies have consistently demonstrated that outcomes for patients treated at the Vanguard Urologic Institute compare favorably with those experienced by patients at other top academic institutions nationwide.

This ongoing program, led by Dr. Slawin, improves outcomes for the patients of all of Vanguard Urologic Research Foundation physicians. back to top

proPSA screening test for prostate cancer

The PSA (prostate specific antigen) blood test is an important screening tool for prostate cancer, the most common solid-tumor malignancy in the United States. While an elevated PSA level may indicate the presence of prostate cancer, it doesn’t always because benign conditions can also elevate PSA level.

Since 1998, the FDA has approved a method to obtain more conclusive results. By calculating the ratio of the level of “free,” or unbound, circulating PSA with the standard total PSA level, physicians can better differentiate patients who have prostate cancer from those who do not, with higher ratios indicating a lower risk of prostate cancer. “The PSA test has become like measuring cholesterol,” says Kevin Slawin, M.D. “You used to just get your cholesterol checked, but now we look at the ratio of LDL and HDL cholesterol levels to predict the risk of heart disease. In a similar way, the free-to-total PSA ratio can predict the risk of prostate cancer.”

Dr. Slawin was instrumental in performing the pivotal studies of the free PSA test that led to an important publication in the prestigious Journal of the American Medical Association and FDA approval later that year. Now, once again, he is a leading investigator of a pivotal trial of novel forms of PSA, pro-PSA, and B-PSA, discovered in his laboratory in 2000, that may further enhance the performance of PSA as a screening test for prostate cancer. Clinical trials have shown positive results, leading Beckman Coulter Inc., the manufacturer of the test, to initiate the current trial. If the positive results are confirmed, FDA approval could follow shortly.back to top

BP-GMAX-CD1 prostate cancer vaccine

The current standard of care for androgen-independent prostate cancer (AIPC) is administration of FDA-approved docetaxel chemotherapy, which yields only a two-month increase in median survival rates and is often accompanied by serious side effects, including fatigue, hair loss, and neuropathy.

In the fall of 2008, researchers at the Vanguard Urologic Institute and Texas Prostate Center at Memorial Hermann - Texas Medical Center will begin participating in a trial to test an innovative vaccine technology expected to offer men an important new treatment option.

The BP-GMAX-CD1 cancer vaccine is specifically designed to circumvent the obstacles researchers believe underlie the failure, to date, of cancer vaccines to fulfill their potential as a potent and safe treatment. Created by Dr. Slawin in collaboration with Baylor College of Medicine researcher David Spencer, Ph.D., the promising new therapy is the first vaccine that can be “activated” precisely at the optimal time and location in the body through administration of an activating agent called AP1903.

AP1903 acts as a molecular “key” that exactly fits a complementary molecular “switch” engineered into the cells comprising the vaccine product. The agent is administered to patients once vaccinated cells have traveled to local lymph nodes, where activation leads to a potent immune response against the targeted malignancy, in this case, prostate cancer.

Based on pre-clinical studies that demonstrated eradication of established experimental tumors in mice, including aggressive B16 melanomas, Drs. Slawin and Spencer pursued FDA approval for a Phase I/II clinical trial of the vaccine in 24 to 36 men who have progressive AIPC. “We’re pleased that the FDA has allowed us to move forward, and we’re very excited to be on the cusp of treating our first patient with the new technology,” Dr. Slawin says.

Trial participants will first undergo a leukapheresis procedure in which white blood cells are collected for processing and then transformed into the dendritic cell-based vaccine BP-GMAX-CD1 over a three-week period. Next they will receive an intradermal injection of their patient-specific BP-GMAX- CD1 vaccine either once a week or once every other week for a total of six doses. The day after each vaccination dose, they will receive a two-hour IV infusion of AP1903. Patients who remain progression-free after the acute phase will be eligible to receive a booster dose of vaccine and AP1903 every eight weeks. All procedures will be conducted on an outpatient basis at the Memorial Hermann -TMC Clinical Research Unit under the auspices of the University of Texas Center for Clinical and Translational Sciences.

“If results are promising, we’ll move to Phase II and then test the vaccine for efficacy with other types of cancer,” says Dr. Slawin. “We believe it can be applied very broadly as an anti-cancer vaccine technology with other types of malignancy.”

For more information about the BP-GMAX-CD1 vaccine or to inquire about enrolling a patient in the trial, please visit www.clinicaltrials.gov at this link.back to top

Establishing an ultrasensitive PSA as the test of choice for determining the likelihood of cancer recurrence after prostatectomy

Most patients who have undergone radical prostatectomy surgery for the treatment of prostate cancer, performed either robotically or through an open approach, are followed after surgery with PSA blood testing. Typically, this is performed every three months during the first year, every six months in years two through five, and once a year thereafter.

Using a standard PSA blood test, an undetectable PSA level reported to the lower limit of most assays (<0.1 ng/mL) has typically been accepted as indication that a patient is cancer-free. However, in a study reported last year, Dr. Slawin and his colleagues demonstrated that an ultrasensitive PSA assay that reports results down to <0.003 ng/mL enables patients with prostate cancer recurrence to be identified well before the less accurate PSA test can identify them. Further, the additional lead time has provided the opportunity to treat them with salvage radiation therapy when the PSA is lower and the cancer is more likely to respond favorably.

As a result of this important study, numerous follow-up studies with collaborating institutions, including Memorial Sloane Kettering Cancer Center, are underway to validate these observations. This is a further example of the power of integrating routine patient cancer treatment and data capture in the Caisis™ database to allow our researchers to make important discoveries regarding the optimal diagnosis and treatment of prostate cancer and other urological diseases.back to top

Avance™ nerve graft

Vanguard Urologic Institute founders Kevin Slawin, M.D., and Tung Shu, M.D., have long been leaders in the development of minimally invasive techniques for radical prostatectomy using the da Vinci® surgical system. The outcomes speak for themselves: minimized damage to tissues surrounding the prostate and excellent cancer control rates that are equivalent to the traditional open approach to radical prostatectomy. Results also include decreased length of stay and decreased morbidity as measured by a more rapid recovery of potency and continence.

But when cancer has spread beyond the prostate, one or both cavernous nerves adjacent to the prostate may require partial or complete removal to ensure a negative surgical margin. The nerves, essential for erectile function and, to a lesser degree, urinary continence, are typically left unrepaired. At the Vanguard Urologic Institute, Drs. Slawin and Shu offer nerve grafting at the time of prostatectomy, providing patients with an increased chance of recovering sexual potency following the healing process.

“We’ve published our results demonstrating improved outcomes in continence and potency in men who require neurovascular bundle resection, either unilateral or bilateral, and undergo sural nerve graft procedures at the time of their initial surgery,” says Dr. Slawin. “The availability of the new Avance™ nerve graft allows us to perform the procedure without removing from the patient the autologous sural nerve that is associated with loss of sensation and occasional pain at the donor site. Ease of handling and the superior length of the Avance nerve graft has made it the preferred graft material for our doctors performing cavernosal nerve graft reconstruction in men undergoing prostatectomy for locally advanced disease.”

Drs. Slawin and Shu were the first in the United States to use the Avance nerve grafts to repair cavernous nerves robotically. Processed by AxoGen, a pioneer in peripheral nerve grafting and nerve regeneration technologies, the graft allows injured peripheral nerves to be repaired using allograft nerves, enabling axon regrowth, as well as restoration of sensation and function to the affected nerves. A breakthrough in nerve technology, the Avance graft provides an environment for nerve fiber regeneration through a biological support structure with inherent growth promoters. Because the graft is decellularized, it allows guided nerve regeneration without immunosuppression.

“At the Vanguard Urologic Institute, we’re constantly looking for new technologies to help us improve the care we provide,” says Dr. Shu. “The Avance nerve graft has allowed us to capture the benefits of nerve grafting for select patients undergoing radical prostatectomy, while eliminating the potential side effects associated with the use of autologous sural nerves for the graft.”

For more information about the Avance nerve graft, contact Dr. Kevin Slawin at 713-366-7800 or via e-mail at kevin.slawin@vanguardurology.com.back to top

Dr. Kevin Slawin

Dr. Slawin has focused his research efforts on translational medicine throughout his career. One example is the discovery of BPH-A and -2proPSA, molecular forms of free PSA that are now on the cusp of FDA approval and that will allow better distinction of the causes of elevated PSA levels in patients. Studies published by Dr. Slawin and his research associates have identified and validated novel molecular markers of prostate cancer progression, and he has developed electronic nomograms that assist physicians in establishing the risk of prostate cancer progression for individual patients. (See www.prostatecenter.com and www.drslawin.com.) These are his current research programs:

Click on any topic for more detail.

Improving outcomes after robotic prostatectomy

Over the years, outcomes after prostate cancer treatment have steadily improved because of increasing physician skill and experience and the integration of new technologies such as robotic prostatectomy, nerve grafting, cryotherapy, and image-guided approaches to external beam radiotherapy. Numerous published studies have demonstrated that physician experience is a key determining factor in cancer cure rate, complication reduction, and recovery rate after open and minimally invasive approaches to prostate cancer surgery, like robotic prostatectomy.

Dr. Slawin has developed and maintained the secure, online, relational Caisis™ database, which contains all cancer and quality-of-life data available on every patient who has received treatment under his direction while he was the Director of The Baylor Prostate Center, and more recently, since he became Director of the Texas Prostate Center in the Vanguard Urologic Institute.

All patients complete a comprehensive, validated, quality-of-life questionnaire before treatment, which is shared with researchers at Memorial Sloane Kettering Cancer Center (MSKCC), and each patient provides additional information periodically after treatment, which is also stored in the Caisis database. Analysis of these data has led to numerous publications and presentations at national academic meetings reporting key insights on how to more effectively manage prostate cancer patients to maximize both cure rates and quality of life after treatment.

With the patient data in the Caisis system as the foundation for a thorough and systematic continuous “quality improvement” program, subtle changes in surgical techniques can be evaluated in an accurate and unbiased manner with respect to their effects on important outcomes. Researchers at the Vanguard Urologic Institute and Texas Prostate Center have been able to develop unique techniques for performing prostate cancer surgery, both open and robotic, that are tailored to individual patient circumstances and that have been proven to lead to the best achievable results.

The Caisis database platform has enabled Dr. Slawin to easily compare and combine data with other top academic institutions, like MSKCC, in order to perform multicenter studies for validation of observations from smaller, single-center studies. For example, in the prestigious Journal of the American Medical Association, Dr. Slawin was able to publish, as the supervising investigator, an important multicenter study demonstrating the effectiveness of salvage radiation therapy for patients with cancer recurrence after radical prostatectomy. These studies have consistently demonstrated that outcomes for patients treated at the Vanguard Urologic Institute compare favorably with those experienced by patients at other top academic institutions nationwide.

This ongoing program, led by Dr. Slawin, improves outcomes for the patients of all of Vanguard Urologic Research Foundation physicians. back to top

proPSA screening test for prostate cancer

The PSA (prostate specific antigen) blood test is an important screening tool for prostate cancer, the most common solid-tumor malignancy in the United States. While an elevated PSA level may indicate the presence of prostate cancer, it doesn’t always because benign conditions can also elevate PSA level.

Since 1998, the FDA has approved a method to obtain more conclusive results. By calculating the ratio of the level of “free,” or unbound, circulating PSA with the standard total PSA level, physicians can better differentiate patients who have prostate cancer from those who do not, with higher ratios indicating a lower risk of prostate cancer. “The PSA test has become like measuring cholesterol,” says Kevin Slawin, M.D. “You used to just get your cholesterol checked, but now we look at the ratio of LDL and HDL cholesterol levels to predict the risk of heart disease. In a similar way, the free-to-total PSA ratio can predict the risk of prostate cancer.”

Dr. Slawin was instrumental in performing the pivotal studies of the free PSA test that led to an important publication in the prestigious Journal of the American Medical Association and FDA approval later that year. Now, once again, he is a leading investigator of a pivotal trial of novel forms of PSA, pro-PSA, and B-PSA, discovered in his laboratory in 2000, that may further enhance the performance of PSA as a screening test for prostate cancer. Clinical trials have shown positive results, leading Beckman Coulter Inc., the manufacturer of the test, to initiate the current trial. If the positive results are confirmed, FDA approval could follow shortly.back to top

BP-GMAX-CD1 prostate cancer vaccine

The current standard of care for androgen-independent prostate cancer (AIPC) is administration of FDA-approved docetaxel chemotherapy, which yields only a two-month increase in median survival rates and is often accompanied by serious side effects, including fatigue, hair loss, and neuropathy.

In the fall of 2008, researchers at the Vanguard Urologic Institute and Texas Prostate Center at Memorial Hermann - Texas Medical Center will begin participating in a trial to test an innovative vaccine technology expected to offer men an important new treatment option.

The BP-GMAX-CD1 cancer vaccine is specifically designed to circumvent the obstacles researchers believe underlie the failure, to date, of cancer vaccines to fulfill their potential as a potent and safe treatment. Created by Dr. Slawin in collaboration with Baylor College of Medicine researcher David Spencer, Ph.D., the promising new therapy is the first vaccine that can be “activated” precisely at the optimal time and location in the body through administration of an activating agent called AP1903.

AP1903 acts as a molecular “key” that exactly fits a complementary molecular “switch” engineered into the cells comprising the vaccine product. The agent is administered to patients once vaccinated cells have traveled to local lymph nodes, where activation leads to a potent immune response against the targeted malignancy, in this case, prostate cancer.

Based on pre-clinical studies that demonstrated eradication of established experimental tumors in mice, including aggressive B16 melanomas, Drs. Slawin and Spencer pursued FDA approval for a Phase I/II clinical trial of the vaccine in 24 to 36 men who have progressive AIPC. “We’re pleased that the FDA has allowed us to move forward, and we’re very excited to be on the cusp of treating our first patient with the new technology,” Dr. Slawin says.

Trial participants will first undergo a leukapheresis procedure in which white blood cells are collected for processing and then transformed into the dendritic cell-based vaccine BP-GMAX-CD1 over a three-week period. Next they will receive an intradermal injection of their patient-specific BP-GMAX- CD1 vaccine either once a week or once every other week for a total of six doses. The day after each vaccination dose, they will receive a two-hour IV infusion of AP1903. Patients who remain progression-free after the acute phase will be eligible to receive a booster dose of vaccine and AP1903 every eight weeks. All procedures will be conducted on an outpatient basis at the Memorial Hermann -TMC Clinical Research Unit under the auspices of the University of Texas Center for Clinical and Translational Sciences.

“If results are promising, we’ll move to Phase II and then test the vaccine for efficacy with other types of cancer,” says Dr. Slawin. “We believe it can be applied very broadly as an anti-cancer vaccine technology with other types of malignancy.”

For more information about the BP-GMAX-CD1 vaccine or to inquire about enrolling a patient in the trial, please visit www.clinicaltrials.gov at this link.back to top

Establishing an ultrasensitive PSA as the test of choice for determining the likelihood of cancer recurrence after prostatectomy

Most patients who have undergone radical prostatectomy surgery for the treatment of prostate cancer, performed either robotically or through an open approach, are followed after surgery with PSA blood testing. Typically, this is performed every three months during the first year, every six months in years two through five, and once a year thereafter.

Using a standard PSA blood test, an undetectable PSA level reported to the lower limit of most assays (<0.1 ng/mL) has typically been accepted as indication that a patient is cancer-free. However, in a study reported last year, Dr. Slawin and his colleagues demonstrated that an ultrasensitive PSA assay that reports results down to <0.003 ng/mL enables patients with prostate cancer recurrence to be identified well before the less accurate PSA test can identify them. Further, the additional lead time has provided the opportunity to treat them with salvage radiation therapy when the PSA is lower and the cancer is more likely to respond favorably.

As a result of this important study, numerous follow-up studies with collaborating institutions, including Memorial Sloane Kettering Cancer Center, are underway to validate these observations. This is a further example of the power of integrating routine patient cancer treatment and data capture in the Caisis™ database to allow our researchers to make important discoveries regarding the optimal diagnosis and treatment of prostate cancer and other urological diseases.back to top

Avance™ nerve graft

Vanguard Urologic Institute founders Kevin Slawin, M.D., and Tung Shu, M.D., have long been leaders in the development of minimally invasive techniques for radical prostatectomy using the da Vinci® surgical system. The outcomes speak for themselves: minimized damage to tissues surrounding the prostate and excellent cancer control rates that are equivalent to the traditional open approach to radical prostatectomy. Results also include decreased length of stay and decreased morbidity as measured by a more rapid recovery of potency and continence.

But when cancer has spread beyond the prostate, one or both cavernous nerves adjacent to the prostate may require partial or complete removal to ensure a negative surgical margin. The nerves, essential for erectile function and, to a lesser degree, urinary continence, are typically left unrepaired. At the Vanguard Urologic Institute, Drs. Slawin and Shu offer nerve grafting at the time of prostatectomy, providing patients with an increased chance of recovering sexual potency following the healing process.

“We’ve published our results demonstrating improved outcomes in continence and potency in men who require neurovascular bundle resection, either unilateral or bilateral, and undergo sural nerve graft procedures at the time of their initial surgery,” says Dr. Slawin. “The availability of the new Avance™ nerve graft allows us to perform the procedure without removing from the patient the autologous sural nerve that is associated with loss of sensation and occasional pain at the donor site. Ease of handling and the superior length of the Avance nerve graft has made it the preferred graft material for our doctors performing cavernosal nerve graft reconstruction in men undergoing prostatectomy for locally advanced disease.”

Drs. Slawin and Shu were the first in the United States to use the Avance nerve grafts to repair cavernous nerves robotically. Processed by AxoGen, a pioneer in peripheral nerve grafting and nerve regeneration technologies, the graft allows injured peripheral nerves to be repaired using allograft nerves, enabling axon regrowth, as well as restoration of sensation and function to the affected nerves. A breakthrough in nerve technology, the Avance graft provides an environment for nerve fiber regeneration through a biological support structure with inherent growth promoters. Because the graft is decellularized, it allows guided nerve regeneration without immunosuppression.

“At the Vanguard Urologic Institute, we’re constantly looking for new technologies to help us improve the care we provide,” says Dr. Shu. “The Avance nerve graft has allowed us to capture the benefits of nerve grafting for select patients undergoing radical prostatectomy, while eliminating the potential side effects associated with the use of autologous sural nerves for the graft.”

For more information about the Avance nerve graft, contact Dr. Kevin Slawin at 713-366-7800 or via e-mail at kevin.slawin@vanguardurology.com.back to top